Takotsubo cardiomyopathy in the peripartum period: a report of 3 cases

¹Obstetrical Intensive Care Unit, Mother and Child University Hospital of Harouchi, Casablanca, Morocco

^&Corresponding author
Loubna Benaddi, Obstetrical Intensive Care Unit, Mother and Child University Hospital of Harouchi, Casablanca, Morocco

Introduction    

Takotsubo cardiomyopathy (TCM) also known as stress induced cardiomyopathy is an uncommon heart disease seen in the peripartum period. It was originally described in Japan in 1990s. Tako-means octopus and tsubo-means jar which was used to trap octopus, its shape evoking the left ventricular apical ballooning in this disease [1]. Takotsubo cardiomyopathy is characterized by new onset of left ventricular dysfunction with variable wall motion abnormalities in the absence of obstructive coronary artery disease often related to an emotional or physical stressful event, most often identified in the preceding days [2]. It is a cardiac emergency and a diagnosis of exclusion. While about 2% of all pregnancies experience some type of cardiovascular complication, TCM during pregnancy or the immediate postpartum period represents an infrequent diagnosis. In fact, majority of TCM cases in pregnancy are described in the peripartum period making it difficult to differentiate TCM from peripartum cardiomyopathy [3]. Several diagnostic criteria have been developed to guide the TCM diagnosis over the years. In this article, we describe cases of Takotsubo cardiomyopathy that were diagnosed in our obstetrical intensive care unit (ICU).

Patient and observation     

Patient 1

Patient information: a 23-year-old, primigravida, married for 2 years, without any medical history was brought to our intensive care unit (ICU) for acute respiratory failure in the immediate post-partum.

Timeline to current episode: prior to administration of spinal anesthesia, she had no cardiorespiratory complaints. Her Heart rate (HR) was 86 pulse per minute with normal sinus rhythm. The anesthesiologist reported that she had an acute episode of hypotension after the administration of spinal anesthesia, which was corrected with 10 mg of ephedrine. The baby was delivered by cesarean section (CS) and an injection of 10 units of oxytocin 10 was administered. She had a satisfying uterine tonicity.

Clinical findings: in the immediate post-operative period, she presented signs of respiratory failure. She became polypneic, with bilateral crackles heard in the pulmonary auscultation, Sp02 was 82% at ambient air. She was then transferred to our ICU. Her bood pressure (BP) started to gradually reduce to 86/40 mmHg, with a HR of 150/min. We put her on non-invasive ventilation at first with norepinephrine. Thirty (30) minutes later, she became confused, with a Glasgow coma scale of 10/15, without any improvement of her vitals. The decision was to proceed to orotracheal intubation and mechanical ventilation, under sedation and 1 mcg/kg/min of norepinephrine (Figure 1).

Diagnostic assessment: an echocardiography was done showing a global hypokinesia with severe left ventricular (LV) dysfunction more in apical and mid segments with ejection fraction about 28%. There was no evidence of pulmonary artery hypertension, right atrial or right ventricular dilatation to suggest pulmonary thrombo-embolism (Figure 2). Blood investigations revealed elevated cardiac biomarkers: Hs-troponin at 5800 and B-Type Natriuretic Peptide (BNP) at 900. Our patient was in cardiogenic shock. We added dobutamine at 10 gamma/kg/min at first.

Therapeutic interventions: regarding the worsening of her vitals, we needed to raise the doses of vasopressors and inotropes. We added antibiotics for the pulmonary infection she had developed. We daily monitored her vitals, arterial blood gas, and biological exams. She started improving gradually at the fourth day, sedation was then reduced. At the sixth day, we were able to extubate our patient given her good and reassuring evolution. The bed side echocardiography showed a slight improvement in her ejection fraction 38% vs 28%.

Follow-up and outcome of interventions: Takotsubo cardiomyopathy as well as peripartum cardiomyopathy were suspected as per clinical, laboratory, coronary angiography and echo findings. As the patient condition improved gradually without specific treatment, TCM was the most logical diagnosis. She was put off vasopressors and inotropes in the 8^th day. We started beta blockers, continued with a low dose of diuretics. The patient was discharged from our ICU on the 10^th day and transferred to cardiology. A cardiac magnetic resonance was done, 3 weeks after her transfer to cardiology, which showed characteristics of TCM: presence of wall oedema and late gadolinium enhancement (Figure 3). She gradually improved her ventricular function and continued her follow up with the cardiology team.

Patient 2

Patient information: a 24-year-old Moroccan pregnant woman (gravida 2, para 2) was transported to the University Hospital of Casablanca due to preterm labor. Her pregnancy was a spontaneous monochorionic diamniotic twin pregnancy. She had no known pre-existing cardiomyopathy or cardiovascular risk factors, such as obesity, smoking, or a family history of cardiovascular diseases.

Clinical findings: upon admission, nicardipine was administered intravenously for tocolysis. To suppress uterine contractions, the dose of nicardipine was gradually increased, and betamethasone (12 mg) was injected twice intramuscularly at 33 weeks of gestation. At 33 weeks + 4 days of gestation, premature rupture of membranes was diagnosed. Consequently, an emergency cesarean delivery was performed under standard spinal anesthesia.

Timeline of current episode: following the administration of spinal anesthesia, she became hypotensive, and 8 mg of ephedrine was administered intravenously. Just after the birth of two girls (weighing 1760 g and 1850 g; Apgar scores of 9/10 and 10/10), her percutaneous oxygen saturation fell to 95%, and she was supplemented with 5 L/min of oxygen. Otherwise, the cesarean delivery was uneventful. One hour after her transfer to the ICU, the patient presented with hypotension at 7/4 mmHg, requiring fluid resuscitation with the use of norepinephrine. The patient began to desaturate to 88%, then to 80%, with signs of respiratory distress and crackles in both lung fields. A lung ultrasound revealed B-lines indicative of acute pulmonary edema.

Diagnostic assessment: transthoracic echocardiography revealed extensive hypokinesia in the basal segments of the anterior, inferior, and lateral walls, with preserved function in the apical segments (Figure 4). The ejection fraction was 35%.

Therapeutic interventions: laboratory data showed no elevation in serum myocardial enzymes, but an elevation of BNP at 350 pg/ml. Furosemide and dobutamine at 10 gamma/kg/min were continuously infused. A coronary angiography was done the fourth day of hospitalization, which was normal without coronary disease (Figure 5).

Follow-up and outcome of interventions: clinical improvement was observed on the seventh day. On the sixteenth day, the patient was transferred to cardiology but her cardiac function normalized after 5 months since on set of symptoms. After suspecting this condition to either be a Takotsubo cardiomyopathy or a peripartum cardiomyopathy, it was only after the normalization of her cardiac function after all this time that we concluded to the diagnosis of inverted Takotsubo.

Patient 3

Patient information: a 30-year-old Ivorian woman (gravida 3, para 1) residing in Morocco for the past 2 years was admitted at 38 weeks of gestation for spontaneous labor. Her pregnancy was a single fetus pregnancy without major complications. She had no known history of cardiomyopathy or cardiovascular risk factors, such as obesity, smoking, or a family history of cardiovascular diseases. Her obstetric history included an ectopic pregnancy and a living child born by cesarean section due to non-reassuring fetal status.

Clinical findings: at 38 weeks of gestation, due to breech presentation on an uterus with a previous cesarean section scar, an emergency cesarean section was performed under standard spinal anesthesia. Following the administration of spinal anesthesia, she became hypotensive and was administered low-dose norepinephrine at 0.05 gamma/kg intravenously. In the immediate postpartum, her percutaneous oxygen saturation dropped to 93%, and she was supplemented with 5 L/min of oxygen. Otherwise, the cesarean delivery was uneventful.

Timeline of current episode: during the postoperative period, urine output decreased after 2 hours and she developed sudden dyspnea and respiratory distress 5 hours later. The patient was transferred to our intensive care unit and was intubated for respiratory support as her oxygen saturation (SpO2) dropped to 70% and a gradual deterioration of consciousness was observed.

Diagnostic assessment: blood tests showed positive troponin levels and negative D-dimer levels. The transthoracic echocardiography showed low left ventricular ejection fraction (LVEF): 27% and a moderate pericardial effusion was observed as well.

Therapeutic interventions: the patient was treated with furosemide and dobutamine at 15 gamma/kg/min in the intensive care unit. Urine output was satisfactorily restored, leading to a reduction in pulmonary congestion. She was extubated at her tenth day of stay. An echocardiography performed after stabilization confirmed an ejection fraction of 42% with no wall motion abnormalities.

Follow-up and outcome of interventions: heart failure symptoms steadily resolved after 17 days with complete recovery of cardiac function on echocardiography after 28 days. A cardiac MRI was performed a month after her admission, it showed normal wall contraction without edema which meant a complete recovery and it confirmed the diagnosis of Takotsubo cardiomyopathy (Figure 6).

Informed consent: all the patients gave their informed consent.

Discussion     

Women of childbearing age are rarely diagnosed with cardiomyopathy during pregnancy in general. Most cases of Takotsubo cardiomyopathy (TCM) in hospitalized patients in the United States (0.02% prevalence) occur in postmenopausal women [4]. The exact cause of takotsubo cardiomyopathy is not known. However, proposed pathophysiological mechanisms include transient coronary artery spasm, catecholamine excess, microvascular dysfunction triggered by an unclear mechanism. The common triggers of TCM include emotional or psychological stressors with a higher incidence seen in patients with preexisting psychiatric conditions. However, up to 20% of affected patients have no identifiable stressors [5].

Considering that several previous reports showed peripartum TCM tends to occur after cesarean section (CS), it might represent a predisposing factor of peripartum TCM. Since one of the major pathogeneses for TCM is the cardiotoxicity caused by catecholamines. The intense emotional and physical stress related to labor and CS as well as catecholaminergic stimulation by uterotonic and tocolytic drugs could be pathogenic for peripartum TCM. Furthermore, the abrupt drop of estrogen, which has a protective effect on the cardiovascular system caused by placenta expulsion might also underly the pathophysiology for peripartum TCM. During pregnancy it is usually prevalent in women with some high-risk factors like age >35 years, multiple gestation, preterm birth, tocolytics, caesarean section (CS), postpartum hemorrhage and use of uterotonics, inotropes and/or vasopressors were also known to be precipitating factors for developing TCM [6].

Hypo or akinesia usually occurs in apical segment of left ventricle in majority of the cases and uncommonly in midsegment or basal segments. When it occurs in basal segment of the left ventricle, it is termed as reverse or inverted takotsubo cardiomyopathy such as seen in the second case [3]. Patients usually present with chest pain, some with breathlessness and it can occur even during the time of caesarean or shortly after. The clinical presentation of TCM and Peri-partum cardiomyopathy (PPCM) is sometimes similar in that both of them are associated with peripartum-on set of heart failure accompanied by systolic cardiac dysfunction in women without history of heart disease before that perinatal period. In the case report by Tomida et al. their patient also showed symptoms of heart failure (HF) such as dyspnea with a reduced left ventricular ejection fraction (LVEF) of 20% soon after cesarean section (CS) [7].

Based on the totally different pathophysiology as well as clinical prognosis between peripartum TCM and PPCM, it is necessary to carefully evaluate and distinguish these different clinical entities in order to give the proper treatment for each. Yang et al. reported that PPCM showed the wide-ranging timing of symptoms (from 14 days before delivery to 30 days after delivery), while the onset of almost all peripartum TCM was seen early after delivery even during the CS. The diagnosis of TCM should be strongly considered in patients after CS, as well as patients with the event of a traumatic or complicated delivery (such as severe eclampsia or severe postpartum hemorrhage) [3]. Furthermore, PPCM is known to be associated with relatively poor prognosis, while the patients with peripartum TCM usually completely recover in a short period of time. Thus, the diagnosis will be retrospective [8]. In fact, we concluded to the diagnosis only after noticing improvement in the left ventricular function in our patients.

Careful history taking is quite important because there are many other possible diseases for differential diagnosis other than peripartum TCM and PPCM, such as latent pre-existing cardiomyopathy, coronary disease, pulmonary edema secondary to eclampsia, myocarditis and amniotic fluid embolism. Bedside echocardiography remains the first line diagnostic tool applied along with clinical examination, electrocardiogram (ECG) and troponin levels. A coronary angiography as well as a cardiac MRI are performed in order to confirm the diagnosis of TCM. In fact, cardiac MRI is very useful to differentiate peripartum TCM from other cardiomyopathies. TCM shows diverse patterns of regional LV wall motion abnormalities, while PPCM shows global hypokinesis, but also presence of wall oedema and late gadolinium enhancement [8].

Takotsubo cardiomyopathy is associated with in-hospital mortality of 2%, in-hospital complication rate of 19% like heart failure, arrhythmias, thrombus formation. Its recurrence rate is up to 5% [9]. Patients with TCM have a good prognosis as they recover soon after delivery within days to 3 months. However, some cases in the postpartum period have been reported with not such good outcomes. A multidisciplinary team approach is essential in managing these patients and should involve cardiologist, obstetrician, neonatologist and anesthetist.

Conclusion     

Pregnancy is considered a hypermetabolic state and it can lead to emotional or physical stress. Additionally, medications, hemodynamic changes during delivery and in some cases, the added risks of cesarean section may lead to Takotsubo cardiomyopathy with various clinical presentations and outcomes. Given the similarity with Peripartum cardiomyopathy (PPCM), finding the true incidence of TCM is difficult. Still, we must be able to differentiate between them as TCM has complete recovery compared to PPCM, which may have some residual left ventricular dysfunction. The two can be differentiated if given more attention to triggering factors, clinical features, and echocardiographic findings. Although TCM is known to be reversible, there is still a risk for mechanical ventilation, need for vasopressors/inotropes and advanced therapies. These cases that we reported may not represent all patients with TCM in pregnancy as they are other cases with a not so fortunate outcome.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

All authors have contributed to write the manuscript. Patient management: Loubna Benaddi, Tebbaa Hessani, Jad Jabouri. Data collection: Loubna Benaddi, Jad Jabouri and Amine Raja. Manuscript drafting: Amine Raja, Yassine Hafiani. Manuscript revision: Smael El Youssoufi, Said Salmi. All authors have read and approved the final version of the manuscript.

Figures     

Figure 1: electrocardiography showing sinus tachycardia with repolarization disorder

Figure 2: apical 4 chamber view of echocardiography showing a global hypokinesia with severe left ventricular dysfunction

Figure 3: cardiac MRI T2 STIR image showing wall edema located in apical and mid planes of left ventricle (LV)

Figure 4: apical 4 chamber view of echocardiography during systole showing dyskinesis of the basal-mid anterolateral, and basal-mid inferoseptal walls

Figure 5: patient 2 coronary angiography showing normal left anterior descending artery (LAD) and circumflex artery

Figure 6: cardiac MRI image during diastole showing normal wall contraction in apical segments and no wall edema

References