Spontaneous coronary and vertebral artery dissection in early pregnancy.

A pregnant nulliparous female aged in her early 30s initially presented to the hospital at 11 weeks’ gestation with acute onset chest pain. Her medical history was significant for anxiety, treated with sertraline 50 mg daily, and endometriosis requiring previous micro-ablation surgery. At the time of her presentation, her only other medications were an antenatal multivitamin and progesterone pessaries. She had no allergies. Vaccinations for influenza and COVID-19 were up to date. She worked full time as a primary school teacher. She was a life-long non-smoker, did not use recreational drugs and consumed alcohol socially but none in pregnancy. Family history revealed a sister who experienced a vertebral artery dissection 6 months postpartum, although this was in the context of a motor vehicle accident and possible neck manipulation. Two other sisters were well with no history of cardiovascular events. A maternal grandmother died postpartum, reportedly due to pneumonia. There was no other family history of premature death or cardiovascular events. On presentation to an emergency department without access to obstetrical services, she reported sudden onset burning-type chest pain, arm pain, headache and clamminess. There were non-specific but dynamic ECG changes and high-sensitivity troponin peaked at 387 ng/L (normal range<11 ng/L). A transthoracic echocardiogram (TTE) was normal, as was a CT pulmonary angiogram performed to exclude a pulmonary embolism. Her symptoms resolved, and she was discharged from the emergency department with a plan for outpatient cardiology follow-up. Four days later, she re-presented to a different emergency department, again without access to obstetrical services, with chest and arm pain. ECG changes were consistent with a posteroinferior ST elevation myocardial infarction ( figure 1 ), and troponin peaked at 32 744 ng/L. A diagnosis of SCAD was made based on angiogram findings of an occluded right coronary artery with evidence of dissection. Balloon angioplasty (no stent) was performed with no immediate complications ( figure 2 ). CT brain was unremarkable. Vertebral ultrasound showed likely right-sided vertebral artery dissection. This was confirmed on vertebral artery CT as a >50% narrowing of the mid to distal right vertebral artery and on magnetic resonance angiography showing intramural haematoma from dissection extending from the level of the inferior endplate of C4 to the skull base/the fourth segment of the right vertebral artery ( figure 3 ). The vertebral dissection was managed conservatively. Four days later, recurrent chest pain and acute ECG changes required emergency cardiac catheterisation, which confirmed re-occlusion of the vessel by coronary artery dissection. Due to the extensive nature of the dissection extending to the ostium of the right coronary artery, stent implantation was not attempted due to the risk of dissecting the ascending aorta. A coronary artery bypass graft (CABG) to the right coronary artery was performed. Life-long aspirin (100 mg daily) was commenced. Metoprolol 12.5 mg two times a day was commenced to reduce the risk of subsequent dissection and assist left ventricular recovery, with up-titration recommended as blood pressure allowed. Post-CABG, TTE was reported as showing mild-to-moderate left ventricle function with an estimated ejection fraction of 40%. The basal to mid inferolateral, basal infero-septum and basal to mid inferior walls were akinetic. Renal artery ultrasound showed normal renal arteries without aneurysmal dilatation. Repeat CT and vertebral artery ultrasound were arranged for 6 weeks after the initial presentation. An urgent telehealth consultation occurred with a cardiologist managing a tertiary cardio-obstetrical service while she was recovering in intensive care. She was discharged to community cardiac rehabilitation, and cardio-obstetrical care was arranged in a tertiary maternity hospital. At 13 weeks’ gestation, she had her first joint cardiology and obstetrical appointment. Extensive counselling was provided around the risks of ongoing pregnancy with the patient, her partner and her extended family. She elected to continue the pregnancy. Maternal genetic testing for inherited aortopathies and related conditions was undertaken to guide further counselling and management. Non-invasive prenatal testing was deemed not necessary by the couple as it would not change their management of the pregnancy. All other standard antenatal testing was unremarkable. Six weeks post-CABG, at 19 weeks’ gestation, the repeat TTE showed a mildly dilated left ventricle with moderate systolic dysfunction. Basal and mid posterior walls were severely hypokinetic. The ejection fraction was 40%. At 20+5 weeks’ gestation, the standard morphology ultrasound showed a normal-looking fetus. A single umbilical artery was noted. Frequent review at both a cardio-obstetrics and a high-risk maternal fetal medicine clinic occurred throughout the pregnancy. At 24+5 weeks’ gestation, obstetrical ultrasound performed to assess fetal growth showed a well-grown fetus (estimated fetal weight (EFW) 46th centile, abdominal circumference (AC) 92nd centile). However, when repeated at 28+4 weeks’ gestation, the ultrasound showed a steady fetal growth trajectory (EFW 58% centile, AC 95% centile), but the fetal bowel loops were dilated (18 mm; upper limit of normal (ULN) 15 mm), the stomach was dilated and the anal muscular complex was visible excluding anorectal atresia. At 32+5 weeks’ gestation, obstetrical ultrasound showed dilated bowel loops at 30 mm diameter, suggestive of small bowel atresia. The amniotic fluid index was borderline high at 25 (normal range 5–25), but there was no other evidence of fetal compromise. Neonatology and genetic opinions were sought, and the appearance was thought to suggest jejunal atresia, likely related to a vascular event to the small bowel blood supply. After multidisciplinary discussion, delivery via Caesarean section at 34 weeks’ gestation was planned. This was thought to represent a compromise between the need to minimise the cardiac stress on the mother, acknowledging the possibility of an unrecognised genetic predisposition given the early and severe presentation, while avoiding excessive prematurity for the neonate. Head-to-pelvis non-late gadolinium enhancement magnetic resonance angiography was performed to exclude occult aneurysms, of which none were observed. At 33+4 weeks’ gestation, the patient presented to the maternity hospital with decreased fetal movement. Cardiotocography showed prolonged decelerations (fetal heart rate 80 beats per minute). Emergency Caesarean section resulted in the birth of a live male infant with Apgar’s of 6 at 1 min, 6 at 5 min and 10 at 10 min. The birth weight was 2154 g.

This patient elected not to breastfeed considering both the considerable metabolic demands of lactation and the benefit of additional pharmacotherapy in her recovery. Four days postpartum, the maternal TTE showed moderate segmental left ventricular dysfunction with an ejection fraction of 39%. She was commenced on candesartan 2 mg daily. Contraception with a progesterone-impregnated intrauterine device was strongly advised but, due to patient preference, was not placed. At 6 months postpartum, the patient was participating in moderate-intensity exercise for at least 30 min per day and had no symptoms of heart failure. Stress TTE showed a moderately dilated left ventricle with moderately reduced systolic function. There was no contractile reserve, and indeed, the left ventricle systolic function deteriorated with exercise. Metoprolol was changed to bisoprolol 2.5 mg daily. Candesartan was changed to sacubitril/valsartan 24/26 mg. Dapagliflozin 100 mg daily was started shortly thereafter. The infant was transferred to the neonatal intensive care unit. At 5 days of age, the infant had a laparotomy for 12 jejunal atresias with 9 primary anastomoses. Histopathology showed multiple sections of benign small bowel with central stenosis, with one section showing a collagenous fibrous band which appeared ischaemic. A total of 47 cm of bowel remained in situ. At 6 months of age, the male infant was thriving with a height and weight tracking on the fifth centile. No developmental concerns have been identified. The mother and child dyad was reviewed by the genetics team postpartum. Previously organised genetic testing, including an aortopathy panel (exome) and microarray, had both been normal. All first-degree relatives were advised to have a TTE, with repeated studies at 3- to 5-year intervals if normal. For the offspring of this pregnancy, screening was advised to start in adolescence. Preconception counselling for future pregnancies was discussed, including the potential risk of recurrent SCAD, myocardial infarction, heart failure and death. The safest option was of no further pregnancies, and this is the likely decision of the patient. However, future obstetrical management decisions would involve shared decision-making between the patient, her family and a broad multidisciplinary team.

Spontaneous coronary artery dissection (SCAD) is the most common cause of myocardial infarction in pregnancy. Affected pregnant women are thought to have an underlying predisposition, with the acute dissection being precipitated by hormonal changes weakening the vessel wall and haemodynamic changes increasing the vessel wall stress. 1 Although SCAD is more common in the third trimester of pregnancy and the postpartum period, it can occur in early pregnancy. When this occurs, patients should be counselled about the risk of maternal and fetal morbidity posed by the ongoing pregnancy, and shared decision-making between the patient and a multidisciplinary team should guide clinical care. 2

SCAD is an important cause of acute coronary syndrome and myocardial infarction, particularly among young women with few conventional cardiovascular risk factors. 1 Pregnancy-associated SCAD is the most common cause of myocardial infarction in pregnant women and affects around 1.81/100 000 pregnancies. 3 Pregnancy-associated SCAD usually occurs in the third trimester or postpartum period due to increased blood volume and hormonal changes impacting on the structure and tone of the blood vessels. 1 SCAD in early pregnancy is exceedingly rare, with only a small number of case reports in the literature. 4 6 This is the first case report of multiple vessel dissection in early pregnancy and the first case accompanied by morbidity in the offspring, which could potentially relate to either the vascular event in the mother or an underlying, and yet to be identified, genetic pathology. Known risk factors for pregnancy-associated SCAD are black race, chronic hypertension, lipid abnormalities, chronic depression, migraine, treatment for infertility, multiparity and advanced age at first pregnancy. 3 7 Notably, the case described had none of these risk factors. Fibromuscular dysplasia is the condition most associated with SCAD. 8 Inherited arteriopathies and connective tissue disorders are infrequently reported as the underlying cause of SCAD (<5% of cases). Outside these known genetic conditions, SCAD does not seem to be strongly familial, with a family history being reported in 1.2% of cases. 9 Despite this, it is likely that genetic factors predispose to SCAD, but the rarity and sporadic nature of the condition make it difficult to understand the gene-environment associations. 10 Multiple studies suggest that pregnancy-associated SCAD has a poorer prognosis than SCAD that is unrelated to pregnancy. 11 In a review of 120 cases of pregnancy-associated SCAD, 76% of women presented with ST-segment elevation myocardial infarction. Maternal complications included cardiogenic shock (24%), ventricular fibrillation requiring defibrillation (16%), mechanical support (28%) and in-hospital mortality (4%). 12 It is unclear why pregnancy-associated SCAD is associated with more aggressive and extensive dissections than non–pregnancy-associated SCAD. 3 SCAD should be suspected in young women presenting with cardiac symptoms including chest pain with radiation to the limbs or neck or nausea and vomiting and with few conventional cardiovascular risk factors. ECG may demonstrate an acute myocardial infarction, and cardiac enzymes will be raised. Presentation as an acute coronary syndrome or infarct leads to angiography and diagnosis. Angiography in these cases has a greater risk for iatrogenic catheter-induced dissection of 3.4%, compared with <0.2% in other routine cases. 3 Conservative management is appropriate in most cases, with healing frequently being observed by 1 month. However, urgent intervention may be required in some cases. Myocardial infarction may occur in 5–10% of conservatively managed patients within 7 days of the first presentation. Most of these patients require emergency revascularisation. 3 After initial management, low-dose aspirin is safe to use during pregnancy and breastfeeding and is recommended. Beta-blockers should be considered in those with left ventricular dysfunction, arrhythmias or hypertension. Beta-blockers should also be considered if there is a risk factor for dissection, such as an ongoing pregnancy or a predisposing genetic diagnosis. 3 All patients who have a myocardial infarction caused by SCAD should be referred to cardiac rehabilitation. Special attention should be given to mental health as anxiety and depression are common after SCAD, particularly when it occurs in pregnancy or the postpartum period. The 2018 American Heart Association SCAD Scientific Consensus Statement recommends that women with pregnancy-related SCAD should be advised against subsequent pregnancy due to the high risk of recurrence and the inability to predict recurrence and severity, which limits prevention strategies. 3 For women who wish to pursue future pregnancy and where adoption and surrogacy are not acceptable, women are advised to wait at least 1 year after myocardial infarction before proceeding with pregnancy and ideally to have recovered ventricular systolic function without residual cardiopulmonary symptoms. During pregnancy, multidisciplinary care, continuation of a beta-blocker and rigorous management of hypertension are advised. 2 Reassuringly, Tweet et al reported that most women who did pursue pregnancy after SCAD did not have a recurrence of SCAD in the subsequent pregnancy. 2 At 11 weeks pregnant, I boarded a plane and was suddenly struck by what felt like intense acid reflux, uncontrollable coughing, clamminess and throbbing arm pain. After being taken to hospital by ambulance, I had numerous scans and tests that revealed an elevated troponin level. Doctors couldn’t determine the cause. I was in hospital for 3 days then was cleared to return to work. Two days later, I experienced a throbbing pain on the right side of my neck and head. After a few hours that pain stopped abruptly and was quickly followed by another heart episode, with similar symptoms. As a result, I had an angiogram and was diagnosed with SCAD. I also had a CT scan and ultrasound which diagnosed a vertebral artery dissection. While recovering in hospital, 4 days later I had another heart episode. This resulted in a second angiogram, then open-heart bypass surgery. Following my surgery, I was in excruciating pain and heavily medicated, leading to hallucinations. Doctors informed us that there were no statistics to guide us because my SCAD happened so early in the pregnancy. If I proceeded with the pregnancy I could possibly die or have a stroke, but the likelihood of this was unknown. We faced total uncertainty and felt desolate. Fortunately, my family advocated for me during my vulnerable state and encouraged me to wait a week when I was to be discharged before making any decisions. After resting at home, I was able to make an informed choice which I could not have done while heavily medicated in the hospital. I wanted to give my baby a chance at life. Cardiac rehabilitation was vital to my recovery. Instead of group classes, I received personalised sessions with a physiotherapist, which was essential given the additional stress of a pregnancy-related heart condition. Regular sessions with my psychologist helped me manage the trauma and ongoing emotional, mental and physical challenges. I lent heavily on my husband and our parents who offered constant support. I made significant lifestyle changes to reduce stress, including stopping work and minimising social engagements. After discharge from hospital, my husband and I moved in with my parents for support. Following medical advice, at 22 weeks, we moved into accommodation very close to the hospital. I meticulously followed the advice from the Maternal Fetal Medicine Clinic and the Cardiology Pregnancy Clinic. I was reassured by the constant monitoring, planning and multidisciplinary conversations that took place to care for my baby and me. Following the birth I have continued with cardiac rehabilitation and taking medication. My son and I are thriving. I am so grateful to be here to enjoy him! A pregnant or postpartum woman who presents with symptoms of myocardial ischaemia in the absence of cardiovascular risk factors should be considered as having spontaneous coronary artery dissection (SCAD) until proven otherwise. If SCAD occurs early in pregnancy, the patient should be counselled about the potential maternal and fetal morbidities associated with the ongoing pregnancy. Genetic testing is not required in all cases of pregnancy-associated SCAD. However, genetic testing may be considered where there are features suggestive of an inherited aortopathy or connective tissue disorder such as a family history of these conditions, syndromic examination findings, dissections at multiple sites or recurrent dissections.

Common differentials for chest pain in early pregnancy include musculoskeletal pain, gastro-oesophageal reflux disease and pneumonia. However, life-threatening conditions should always be considered, including pulmonary embolism, aortic dissection and acute coronary syndromes due to atherosclerotic disease or coronary artery dissection. Coronary artery dissection can be spontaneous (SCAD) or, less commonly, be induced by physical trauma. SCAD infrequently occurs in the context of an underlying connective tissue disorder or inherited aortopathy, but this may be considered if there is a family history of these conditions, syndromic examination findings, dissections at multiple sites or recurrent dissections. Although SCAD is more common in pregnancy, in this case, the timing of the events (ie, early pregnancy), the multiple vascular beds involved and the possible family history in the sister were suspicious for an underlying genetic/inherited disorder. Due to the strong association of fibromuscular dysplasia with SCAD, this was thought to be the most likely underlying cause of the presentation. An inherited aortopathy or connective tissue disorder such as vascular Ehlers-Danlos syndrome (COL3A1 mutation) and Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3 mutation) was also considered.