Subsequent Safe Pregnancy with Cesarean Delivery in a Patient with a History of Peripartum Takotsubo Syndrome Complicated by Cardiogenic Shock.

Takotsubo syndrome (TTS) is an acute and reversible heart failure syndrome, usually occurring in females but rarely in the peripartum period. In women with a history of peripartum TTS, it is unclear how to manage subsequent pregnancies. A 39-year-old female with a history of peripartum TTS complicated by cardiogenic shock became pregnant again. She underwent close cardiological follow-up for monitoring left ventricular systolic function and hemodynamic conditions. Epidural anesthesia was preferred to avoid catecholamine surge during cesarean delivery. After a few days of hospitalization, the patient and the newborn were discharged in good health. In our patient with a history of complicated peripartum TTS, close cardiological follow-up, appropriate management therapy, and anesthesia modality allow us to guide safely a new pregnancy.

INTRODUCTION

Takotsubo syndrome (TTS), also known as stress cardiomyopathy or “broken heart syndrome,” is a clinical entity characterized by transient left ventricular (LV) systolic dysfunction and reversible heart failure,[12] usually involving the apex (apical ballooning) and less commonly, the midventricular and basal LV walls.[3] TTS is associated with a relatively good long-term prognosis, as complete recovery of LV systolic function occurs within days or weeks.[4] However, heart failure, cardiogenic shock, and other serious cardiac complications have been reported during the acute phase.[5] Coronary vasospasm, activation of alpha- and beta-adrenergic receptors, neurogenic myocardial stunning, and microvascular dysfunction have been suggested as potential mechanisms.[3] Although the etiology is still unknown, catecholamines seem to play a key role in the pathogenesis of this intriguing syndrome. TTS is often precipitated by an acute emotional or physical stress[67] and is most prevalent among postmenopausal women though increasingly reported in younger patients including premenopausal women during pregnancy or childbirth.[23] Several cases of peripartum TTS have been described in young women experiencing serious complications after cesarean section.[8910] Conversely, only a few cases of pregnant women with a history of peripartum TTS are reported in the literature.[11] Crucial issues that remain to be elucidated are (i) whether patients with previous peripartum TTS should be discouraged from becoming pregnant again, (ii) how this patient population should be followed up during pregnancy and postpartum, and (iii) what is the most appropriate anesthesia modality for cesarean delivery.

CASE REPORT

A 39-year-old female with no relevant anamnestic data apart from a history of peripartum TTS occurred ~4 years previously, became pregnant again. At the time of the first pregnancy, she was admitted to our hospital at 40 weeks of gestation for spontaneous delivery, as described by our group (first case).[12] However, after a long and very painful labor, she underwent cesarean section under spinal anesthesia because of cephalopelvic disproportion. Subsequently, intravenous oxytocin was administered to stimulate uterine contraction. The following day, she complained of increasing dyspnea and developed cardiogenic shock, requiring diuretics, inotropic drugs, and intra-aortic balloon pumping. Coronary arteries were normal. Echocardiography and left ventriculography showed midventricular ballooning and severely reduced LV systolic function. After complete recovery of myocardial contraction, the patient was discharged after 12 days in good health with a diagnosis of peripartum TTS. Between the two pregnancies, she was in good health, taking only beta-blockers for 1 year thereafter. Despite this tremendous experience, she decided to carry the second pregnancy to term.

On the first visit, at 8 weeks of gestation, the patient was asymptomatic, blood pressure was 110/70 mmHg, and heart rate was 80 bpm. Auscultation revealed normal heart sounds, with no cardiac murmurs or pulmonary rales. No ankle swelling was observed. The electrocardiogram (ECG) showed normal sinus rhythm. Transthoracic echocardiography showed normal LV dimensions with good systolic function (ejection fraction 63%). In addition, speckle tracking echocardiography was performed to evaluate global longitudinal strain (GLS) considered an objective index of myocardial deformation. A GLS value of −24% (n.v. <−19.9%) was detected ruling out early subclinical myocardial dysfunction. No signs of diastolic dysfunction and/or increased LV filling pressure were detected. Trivial mitral and tricuspid regurgitation were observed. Pulmonary arterial pressure was within normal limits. No pericardial effusion was appreciated. The patient was informed about the risk of complicated TTS recurrence during the peripartum period and the current lack of guidelines for the management of this challenging situation.

The multidisciplinary team composed by a cardiologist, an anesthesiologist, and a gynecologist decided not to discourage the pregnancy continuation, considering good cardiovascular condition of the patient.

The primary goal was to avoid the events that had previously triggered TTS onset such as painful labor and spinal anesthesia.[812] The multidisciplinary team met to discuss delivery timing, the most appropriate anesthesia modality, and pre- and post-operative monitoring. Frequent cardiological, ECG, and echocardiographic follow-up during pregnancy were substantially unchanged. Owing to the normal course of pregnancy and normal fetal growth, the patient was hospitalized on week 38 of gestation for elective cesarean delivery. Considering the history of peripartum TTS and to select the most appropriate anesthesia technique, three goals had to be met: to minimize sympathetic activation, to reduce catecholamine surge, and to maintain hemodynamic stability avoiding vasoconstrictor drugs.[1314]

Although spinal anesthesia is the preferred regional technique for cesarean section due to simplicity of technique, rapid administration, and onset of anesthesia, it results in more profound and rapid sympathetic block.[13141516] Hypotension following spinal anesthesia is more pronounced in pregnant patients because of increased cephalad spread due to aortocaval compression, compression of the dural sac by the engorged epidural venous plexus, and a reduction in lumbosacral cerebrospinal fluid volume. On these grounds, epidural anesthesia was chosen. This modality provides a slow, smooth, and effective anesthetic block with better hemodynamic stability, avoiding abrupt blood pressure drop and perioperative increased serum level of catecholamines.

At the entrance to the operating room, vital signs were good (blood pressure 108/66 mmHg, oxygen saturation 98%, and body temperature 36.6°C). ECG monitoring demonstrated sinus rhythm with heart rate of 78 bpm.

Under local anesthesia, an epidural catheter was inserted at L3–L4 space and a test dose of 3 ml of lidocaine 2% without epinephrine was injected.

For intraoperative anesthesia, 18 mL ropivacaine 0.75% +10 mcg sufentanil +2 mL saline were given epidurally. A microbolus of 2 mL of solution, for a total of 14 mL, was administered every 2 min until extension of sensory block to T4–S1 was obtained. Cesarean section was started 20 min later. During surgery time (35 min), no vasoconstrictors were necessary as blood pressure variations never exceeded 20%. A term male infant was born, with a birth weight of 3600 g and an Apgar score of 9, 10, and 10 at 1, 5, and 10 min, respectively.

Umbilical cord blood gas analysis revealed an arterial pH of 7.29 and a venous pH of 7.38. After newborn extraction and hysterotomy closure, intravenous oxytocin (5 IU over 5 min followed by 20 IU in 1000 mL saline over 8 h) was administered to minimize cardiovascular effects (hypotension, QTc prolongation, and arrhythmias).[17] No adverse events occurred during surgery.

Three hours later, as sensory block was below T6 and motor block was almost resolved (Bromage score 2), epidural analgesia through an elastomeric pump was initiated with ropivacaine 0.2% and sufentanil 0.5 mcg/mL at a 5 mL/h infusion rate over 48 h.

In the postoperative period, pain control, as assessed by visual analog scale, was satisfying.

Vital signs and hemoglobin level were continuously monitored. Serial ECGs performed during the following 48 h were within normal limits. Frequent ultrasound chest scanning, performed every 2 h for the first 24 h using a pocket-size device, revealed no wall motion abnormalities and good LV systolic function.[18] On the 3rd day, the patient was in good clinical condition, and transthoracic echocardiography with speckle tracking analysis confirmed normal systolic function (ejection fraction 64%, GLS −24%) [Figure 1]. The parturient was discharged on the 7th day without cardiovascular therapy. Cardiological evaluation, ECG, and echocardiographic parameters were substantially unchanged at 1, 3, and 6 months of follow-up [Table 1]. At 1-year clinical follow-up, the mother and the newborn were both in good health. Patient's written informed consent to report the case has been obtained.

Figure 1

Two-dimensional and speckle tracking echocardiography 3 days after cesarean delivery. Apical four-chamber (a), two-chamber (b), and long-axis (c) views by conventional echocardiography (ejection fraction 64%). The time-longitudinal strain curves in the same apical view (e-g) are displayed. The left ventricle is divided into six segments in the long-axis apical view (d), and the segmental global longitudinal strain value is overlaid onto the two-dimensional image. Bull's eye plot (h) displays the regional value of longitudinal strain for 17 segments, and the global longitudinal strain is averaged (−24%)

Table 1

Echocardiographic findings during pregnancy and in postpartum

	LVEDV	LVESV	EF	GLS	E/è	TAPSE	PASP
8 weeks	59	22	63	−24	5	26	19
16 weeks	68	25	64	−24.7	5	30	28
24 weeks	70	28	60	−23.8	5	28	26
28 weeks	74	32	56	−24	6	30	27
32 weeks	89	39	56	−24.5	5	25	19
36 weeks	67	26	61	−21.9	6	28	22
Cesarean section	68	25	63	−23	5	30	20
1 month	87	35	59	−22.4	5	29	21
3 months	76	32	57	−22	6	29	19
6 months	74	31	58	−23.6	5	26	22

E=Protodiastolic wave of mitral inflow, è=Protodiastolic wave of mitral annulus velocity, EF=Ejection fraction, GLS=Global longitudinal strain, LVEDV=Left ventricular end-diastolic volume, LVESV=Left ventricular end-systolic volume, PASP=Pulmonary artery systolic pressure, TAPSE=Tricuspid annulus plane systolic excursion

DISCUSSION

Recently, TTS has been divided into primary and secondary forms, depending on the trigger event and the clinical picture at onset.[3] In particular, secondary TTS often occurs in patients hospitalized for other pathologies who experience an important stress condition (i.e., intensive pain). Cesarean delivery, labor, and abortion have already been reported as possible triggers of secondary pregnancy-related TTS. Peripartum TTS should be included in the differential diagnosis with other diseases associated with pregnancy, such as peripartum cardiomyopathy (PPCM), eclampsia, HELLP syndrome (H: hemolysis, EL: elevated liver enzymes, LP: low platelet count), viral myocarditis, acute coronary dissection, and pheochromocytoma.[1920] To distinguish TTS from PPCM is crucial because of important differences between these two conditions. Compared with TTS, PPCM presents the following features: (1) it usually affects patients with cardiovascular risk factors between the last month of pregnancy and the 6 months after delivery, while TTS symptoms occur early after delivery; (2) it generally causes LV dilatation with depressed systolic function due to diffuse hypokinesis, while in 80% of cases TTS is characterized by hypo-, a-, or dyskinesia of the apical region (ballooning) along with the hypercontractile state of basal segments of the LV; (3) it can be successfully managed with beta-adrenergic inotropes, which are contraindicated in TTS; (4) LV recovery takes longer than in TTS and is incomplete in many patients, with persistent LV systolic dysfunction even at long-term follow-up; and (5) recurrences may develop during subsequent pregnancies, which for this reason are often discouraged, particularly in women with signs or symptoms of heart failure including persistent systolic dysfunction and elevation of biomarkers such as NT-proBNP and troponin.[21] Conversely, in patients with a history of peripartum TTS, subsequent pregnancy should not be systematically discouraged. In this setting, women who become pregnant again should undergo close cardiological follow-up. Owing to its large availability and versatility, conventional echocardiography allows continuous monitoring of LV systolic function and hemodynamic conditions, both during pregnancy and postpartum. In addition, speckle tracking echocardiography enables early identification of subclinical myocardial dysfunction before signs and symptoms of heart failure become apparent.[22] Moreover, bedside echoscopy with pocket-size ultrasound devices is useful to evaluate cardiac function in the operating room and in the early postoperative period.[18]

Before cesarean section, careful selection of the anesthesia technique is another key point. Compared with spinal anesthesia, epidural anesthesia provides a more gradual onset of blockade favoring hemodynamic stability. Finally, it is also important to reduce catecholamine release to avoid or minimize the use of vasoconstrictor or sympathomimetic agents.

CONCLUSION

In our patient with a history of previous TTS complicated by cardiogenic shock, close cardiological and echocardiographic follow-up, appropriate management therapy and anesthesia modality, allowed us to guide safely the subsequent pregnancy, the childbirth with cesarean section, and the postpartum period. Although we reported only a single case, it should be of interest to spread the message that a new pregnancy should be followed with caution but not systematically discouraged in this peculiar setting. During delivery avoiding or minimizing the effect of potential triggers could play a crucial role. For this reason, epidural anesthesia should be preferred for cesarean section. Our conclusion needs to be confirmed in larger series.

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Conflicts of interest

There are no conflicts of interest.