A case of pregnancy-associated acute myocardial infarction with refractory ventricular fibrillation and heart failure

Abstract

Acute myocardial infarction (AMI) is rare among women of childbearing age. Spontaneous coronary artery dissection (SCAD), a rare cause of AMI, is the leading cause of pregnancy-associated acute myocardial infarction (PAMI), and is associated with critical complications, including pump failure, ventricular arrhythmias, and sudden death. Optimal treatment strategies for SCAD and PAMI remain unclear. In this report, we describe a case of PAMI due to SCAD presenting as cardiopulmonary arrest. After comprehensive treatment including advanced cardiovascular life support, emergent percutaneous coronary intervention (PCI), therapeutic hypothermia, and emergent Cesarian section for intrauterine fetal death, she survived without neurological sequelae. Intensive medication for pump failure was subsequently required, and she was discharged with adequately controlled heart failure, despite revealing stent lumen obstruction by cardiac computed tomography. On close follow-up for one year, she has remained free of further cardiac events.

<Learning objective: Pregnancy-associated acute myocardial infarction (PAMI) is a rare but occasionally complicated event. Spontaneous coronary artery dissection is the principal mechanism of PAMI. The clinical presentation of PAMI can range from asymptomatic to cardiac shock and fatal ventricular fibrillation. We aimed to present a sudden cardiac arrest case due to PAMI. Intensive and comprehensive medical care succeeded in her return to spontaneous circulation and discharge without neurological sequelae.>

Introduction

Pregnancy-associated myocardial infarction (PAMI) is an uncommon but devastating disease occurring in 3–10 of every 100,000 pregnancies [1], [2]. The primary cause of PAMI is spontaneous coronary dissection (SCAD), which continues to present substantial management difficulties [3], [4]. There are no guidelines for optimal treatment of this challenging condition. We report the case of a pregnant woman who experienced sudden cardiac arrest due to PAMI caused by SCAD. Subsequent to return of spontaneous circulation (ROSC), the patient suffered from incessant ventricular fibrillation, refractory heart failure, intrauterine fetal death, and anoxic coma. After comprehensive intensive care management, she was eventually discharged without neurological deficits.

Case report

A 37-year-old multiparous woman who was 21-weeks pregnant was brought to the Emergency Department for sudden onset severe chest pain. She had neither a significant past medical history nor a family history of cardiovascular disease. No cardiovascular risk factors were identified except for current smoking. During initial interview, the patient collapsed and was found to be in cardiac arrest; the emergency physician began cardiopulmonary resuscitation (CPR) immediately. Her initial rhythm was ventricular fibrillation (VF; Fig. 1A). Electrical defibrillation restored spontaneous circulation, however, she remained unresponsive. Her heart rate was 125 beats/min, and blood pressure was 137/111 mmHg. On physical examination, her level of consciousness on Glasgow Coma Scale was 6 (E1V2M3), limiting thorough neurological evaluation. Cardiac examination revealed no significant abnormalities except for S3. Myocardial enzymes were normal except for a positive heart-type fatty acid binding protein test. Chest radiograph showed no abnormality, and electrocardiography (ECG; Fig. 1B) showed no remarkable ischemic changes. Echocardiography revealed a hypokinetic anterior wall and apex.

Fig. 1.

(A) Electrocardiogram (ECG) monitor detects ventricular fibrillation. (B) After electrical defibrillation, ECG shows no remarkable ST-T changes or QT prolongation. (C) ECG at discharge reveals diffuse abnormal Q and T-wave inversion on the anterior and inferior leads.

Suspecting acute coronary syndrome, we performed an emergency coronary angiography, which demonstrated 100% occlusion in the proximal left anterior descending artery (LAD) (Fig. 2A); percutaneous coronary intervention (PCI) was subsequently performed. After passing the guide-wire, a spiral dissection of the LAD was evident (Fig. 2B). During procedure, her clinical condition degenerated into refractory VF. In addition to CPR and repeat electrical defibrillation, 300 mg of amiodarone and potassium infusion was administered, resulting in ROSC. Due to ongoing ischemia, we decided to perform a primary coronary stenting to maintain patency of the vessel lumen. Intravascular ultrasound (IVUS) revealed a consecutive and relatively high echoic layer suggestive of collapsed false lumen and intimal flap, ranging from the proximal to distal segment of the LAD, without atherosclerotic changes (Fig. 2Ba–e). These findings were compatible with SCAD and a bare-metal stent (BMS) was implanted to cover the entire length of the dissection. After that, thrombolysis in myocardial infarction (TIMI) grade 3 flow without residual dissection was demonstrated (Fig. 2C), although septal or diagonal branches remained occluded. A peak creatine kinase value was 5105 IU/l. Unfractionated heparin was infused to avoid stent thrombosis instead of the oral antiplatelet agents.

Fig. 2.

(A) Coronary angiographic imaging shows the obstructed proximal left anterior descending artery (LAD) (black arrow). (B) Coronary angiography after guide wire passage through the LAD reveals the spiral dissection (thin black arrow). Intravascular ultrasonography imaging demonstrates intramural hematoma from proximal to middle sections of the LAD (a–e, white asterisks). (C) Angiographic imaging after stent implantation shows normal flow of the LAD without dissections (black asterisk).

As the patient remained unconscious after resuscitation, we initiated therapeutic hypothermia protocols. Body temperature was kept at 34 °C for 24 h, with gradual rewarming performed over the ensuing 48 h.

Four hours after PCI, refractory pulseless ventricular tachycardia, likely due to metabolic acidosis, was noted. Although prompt CPR, repeat defibrillation, and treatment with additional amiodarone resulted in successful resuscitation, fetal heart beat was subsequently lost. Additionally, severe pump failure due to broad infarction, refractory to conventional treatment, was noted, with a peak serum B-type natriuretic peptide (BNP) of 2132.8 pg/ml; echocardiography showed broad anterior akinesis and depressed left ventricular ejection fraction of 30% (Fig. 3A and B). Intravenous infusion of milrinone and carperitide was necessary to maintain adequate hemodynamics.

Fig. 3.

Transthoracic echocardiography and multi-slice computed tomographic imaging. Apical four-chamber view during diastolic phase (A) and systolic phase (B) shows broad anterior akinesia (white arrows) and depressed left ventricular ejection fraction at 30%. (C) Multi-slice computed tomographic imaging of the left anterior descending artery (LAD) performed 3 months after the initial event shows stent thrombosis (white arrow) and distal collateral flow (black arrow). It also shows another coronary dissection in the proximal LAD (*), as well as wall thinning of infarcted area (**).

Six days after admission, elective Cesarian section was performed with delivery of a 450 g stillborn infant. Nonetheless, therapeutic hypothermia improved her neurological function and no subsequent neurological deficits were observed; Modified Rankin score was 0 at discharge. Subsequent to delivery, she was started on aspirin, clopidogrel, carvedilol, candesartan, and spironolactone. As she complained of paroxysmal nocturnal dyspnea after discontinuation of milrinone, the doses of carvedilol and spironolactone were increased gradually. In addition, enalapril and appropriate doses of pimobendan and azosemide were given to avoid use of intravenous inotropes. Her symptoms gradually resolved and serum BNP value improved. Daily medications at discharge were as follows: carvedilol 20 mg, spironolactone 75 mg, candesartan 4 mg, and enalapril 5 mg.

Multi-slice computed tomography performed about two months into admission revealed stent thrombosis with good distal collateral flow (Fig. 3C), and wall thinning of the infarcted area. ECG at discharge revealed diffuse abnormal Q and T-wave inversion on the anterior and inferior leads (Fig. 1C). On hospital day 102, she was discharged without recurrent angina or malignant arrhythmias. As of a year later, she was doing well and without major adverse cardiac events requiring re-admission.

Discussion

Acute myocardial infarction (AMI) in women of child-bearing age is rare. However, pregnancy has been considered to confer a three to fourfold risk of AMI compared with non-pregnant woman of similar age [1], [3]. James et al. reported an AMI incidence of 6.2 per 100,000 deliveries, with a case fatality and mortality rate of 5.1% and 0.35 per 100,000 deliveries, respectively [2]. A current review of the literature reveals that PAMI may occur at any stage of pregnancy, and is especially prevalent during the third trimester or postpartum. Age of patients ranged from 17 to 52 years old; 38–43% were older than 35 years [3], [5]. Multigravidas were found to have more PAMI. Although 25–45% were former/current smokers, the majority of patients did not have traditional coronary risk factors [3], [5].

The pathophysiological mechanism of PAMI is complex. Angiographically or on autopsy, SCAD was reported in 27–43% of patients, whereas atherosclerotic plaque was observed in 27–40% [3], [5]. SCAD is a rare condition with a prevalence of 0.1–1.1% on angiography [4]. Tweet et al. reported an annual incidence of SCAD of 0.26 per 100,000 persons [6]. However, the true incidence of SCAD may be underestimated for three reasons: (1) initial presentation as sudden death, (2) underuse or avoidance of coronary angiography in young women, and (3) under-recognition of angiographic characteristics of the disease [4], [6].

The pathogenesis of SCAD remains unclear, especially in the peripartum period. Increased levels of estrogen and progesterone, enhanced vascular reactivity, or thrombophilia due to pregnancy-related hypercoagulability may be potential underlying causes. Moreover, estrogen and progesterone are thought to produce biochemical and structural changes in arterial walls, such as loss of normal elastic fibers, fragmentation of reticular fibers, and decreases in volume of acid mucopolysaccharides. Moreover, accumulation of released eosinophils and proteases may further lead to cystic medial necrosis. Elevated cardiac output during pregnancy may enhance wall stress, particularly during labor, accompanying cystic medial necrosis and resulting in greater intramural hematoma and subsequent coronary dissection [3], [4], [5].

In the majority (69–78%) of SCAD in PAMI patients, the LAD is affected [1], [3]. In contrast, the incidence of multi-vessel dissection only ranges from 25% to 39% [3], [6]. As a result, broad cardiac infarction or ischemia occurs, which results in a high prevalence of VF [3], [6]. Almost half of patients experience reduction of left ventricular ejection fraction to less than 40%, and 38% of patients suffered from heart failure or cardiogenic shock [3].

The optimal management of PAMI or SCAD remains controversial, with choice of treatment depending on the presence of ongoing ischemia, malignant arrhythmias, information from coronary angiography, and maternal/fetal status. In the absence of remarkable complications, SCAD may be managed conservatively, with primary PCI or coronary artery bypass graft surgery (CABG) reserved for patients with complications due to ongoing ischemia. Nonetheless, several technical aspects warrant consideration. Tweet et al. reported a rate of successful PCI in SCAD of only 65% due to wire migration into the false lumen, as well as propagation of dissection or hematoma from stent implantation. They also report occlusion in 11 of 15 CABG grafts [6]. As such, once PCI is performed, the use of intracoronary imaging to detect extent of dissection, coupled with direct stent techniques, may be the best choice, as was pursued in our case [4], [6]. Despite these modalities, it remains difficult to achieve successful revascularization without complication. In this case, we could not restore the flow of septal or diagonal branches. Dissection extended into ostium of these branches may be the cause. Rather than this pathophysiology, it is feasible that the stent might be implanted into false lumen, and myocardial necrosis might exacerbate consequently. Therefore, it is necessary to pay full attention during the procedure.

In addition to the complex features of PAMI and SCAD, the physiological changes of pregnancy, including anemia, reduced functional residual volume, and limited compensatory capacity for maternal acidosis, may further complicate management. American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, describe the effect of the gravid uterus on diminishing venous return, as well as emphasizing the importance of emergent Cesarian section for inferior vena cava decompression depending on gestational age [7]. As in the present case, the procedure may potentially restore sufficient blood flow, resulting in hemodynamic stability.

Therapeutic hypothermia is the only established and recommended treatment to improve neurological outcome after cardiac arrest coma per international resuscitation guidelines [8]. While this population has been excluded from large studies, several previous case reports have commented on the efficacy and safety of therapeutic hypothermia for pregnant women [9], [10]. Considering the coagulation abnormalities complicating hypothermia, as well as disseminated intravascular coagulation induced by fetal death, we discontinued antiplatelets, using unfractionated heparin instead. As a result, we were able to avoid hemorrhagic complication of Cesarian section delivery, despite running the risk of provoking stent thrombosis.

Although there appears to be improvement in the prognosis of SCAD, Tweet et al. reported an almost 30% rate of recurrence within 10 years, with rates of major adverse cardiac events, including death, recurrent SCAD, myocardial infarction, and congestive heart failure, approaching 50% beyond 10 years [6]. In the present case, although the patient has not experienced untoward cardiac events a year after discharge, close long-term follow-up is warranted.

Conflict of interest

The authors declare no conflict of interest.