Pregnancy-related Spontaneous Coronary Artery Dissection: Two Case Reports and a Comprehensive Review of Literature.

Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome, particularly seen in women during pregnancy or in the puerperium. It has a high acute phase mortality. The etiology is uncertain. Hormonal changes during pregnancy, hemodynamic stress and changes in the autoimmune status have been considered as possible etiological factors. A timely diagnosis and institution of appropriate treatment is important for a successful outcome. There is no consensus of opinion for optimal treatment. Conservative management, coronary artery bypass graft surgery, and percutaneous coronary intervention, all have been described in the literature as possible therapeutic options. Spontaneous coronary artery dissection should be considered as a differential in any young woman presenting with chest pain associated with pregnancy. We report two cases of pregnancy-associated spontaneous coronary artery dissection, both successfully managed, along with a comprehensive review of the previously published literature.

INTRODUCTION

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome (ACS),[12] mainly affecting fairly young[34] otherwise healthy women. About 26 – 38% of cases occur in late pregnancy, peripartum or postpartum.[13-7] The condition mainly involves left main stem or left anterior descending artery or both.[17-10] It was first reported by Pretty,[11] in 1931, in a young Caucasian woman who had a sudden death after developing chest pain. Since then only 116 cases have been reported in the literature. The incidence has been reported to range from 0.1 – 1.1%.[12-15] The etiology of primary SCAD remains uncertain.

Urgent coronary angiography and intravascular ultrasound (IVUS) are indicated in the acute phase in order to establish the diagnosis and determine the best therapeutic approach.[7816] Medical therapy, percutaneous coronary intervention (PCI) and coronary artery-bypass grafting (CABG) have been applied in the acute phase[17] but optimal therapy is yet to be determined.[8] Sudden death is the most common presentation, reported in 60 – 80% of the cases[3] whilst patients may also present with chest pain with or without ECG changes.

We present two cases of pregnancy-related SCAD, both successfully managed, one with conservative treatment and the other with intracoronary stent implantation. A comprehensive review of the published literature since it was first reported in 1931 is presented.

CASE 1

A 41-year-old woman, G3P3, previously fit and well, presented with a history of intermittent chest pains, which started 5 days after an uneventful delivery of her third child. Her chest pain became progressively worse and intolerable, which forced her to call the emergency medical services. The ECG manifested ST elevation across the antero-lateral leads with reciprocal ST depression in the inferior leads [ECG 1].

ECG 1

ECG of case 1 showing ST elevation across the antero-lateral leads with reciprocal ST depression in the inferior leads

She was a smoker and was known to have hypercholesterolemia. The patient denied any illicit drug use. There was no history of any connective tissue disease and no significant family history of ischemic heart disease. Her antiphospholipid antibodies were negative.

She underwent emergency coronary angiography, which demonstrated an occlusion of the LAD at its ostium, with appearances suggestive of dissection and no flow-limiting disease elsewhere [Figure 1a]. The patient underwent primary percutaneous coronary intervention after pre-dilatation and a Vision 3.5 × 28 mm bare metal stent (BMS) was implanted in the LAD [Figure 1b]. The procedure was well tolerated. This led to the restoration of Thrombolysis in Myocardial Infarction (TIMI) III flow, resolution of her pain and ECGs.

Figure 1

Angiography (right anterior oblique cranial projection) of the left anterior descending artery. (a) Initial angiogram demonstrating total occlusion of the proximal left anterior descending artery (arrow); (b) In the same projection as in A, after deployment of a stent in the proximal left anterior descending artery (arrow). Thrombolysis in myocardial infarction (TIMI) III flow was demonstrated. LAD – Left anterior descending artery; LCx - Left circumflex artery

The day after the procedure she became breathless and was found to be in pulmonary edema. She was treated with diuretics. Her subsequent echocardiogram revealed severe impairment of left ventricular systolic function with akinesis of the anterior septum, anterior wall, lateral wall, and apex.

She improved and was discharged home on aspirin, clopidogrel, beta-blocker, ACE-inhibitor, frusemide, and statin.

CASE 2

A 28-year-old woman, G3P3, 3 weeks postpartum, presented with sudden onset of pain in the left arm followed by severe central chest pain without any associated symptoms. She had a similar episode of left arm pain and chest pain a week prior to her presentation, which lasted for a few hours and settled spontaneously. An ECG showed an antero-lateral ST elevation myocardial infarction (STEMI) [ECG 2]. The pain was relieved with intravenous morphine.

ECG 2

ECG of Case 2 showing ST elevation in the antero-lateral leads.

The only cardiovascular risk factor she had was smoking (she had a history of 13-pack years of smoking). There was no history of connective tissue disease and she denied any illicit drug use. The antiphospholipid antibodies were negative. Coronary angiography revealed a dissection of the LAD from the ostium to the first diagonal [Figure 2a]. Her chest pain settled with resolution of her ECGs and she was hemodynamically stable. A decision was therefore made to manage her conservatively. She was commenced on aspirin, clopidogrel, low-molecular weight (LMW) heparin, nitrates, beta-blocker, and ACE inhibitor. She was started on glycoprotein IIb/IIIa inhibitor (Tirofiban) for the next 72 hours. Her echocardiogram demonstrated preserved left ventricular function with normal dimensions and no regional wall motion abnormalities.

Figure 2

Angiography of the left anterior descending artery; (a) Initial angiogram (left anterior oblique caudal projection) showing dissection of the anterior descending artery from the ostium to the first diagonal (arrow); (b) Repeat angiogram (left anterior oblique cranial projection) after one week (arrow); (c) After three months (left anterior oblique caudal projection) (arrow). LAD – Left anterior descending artery; LCx – Left circumflex artery

After one week, a repeat angiogram showed the persistence of the dissection flap but the thrombus had disappeared [Figure 2b]. After 5 days, the patient was discharged home on medical therapy. The patient remained asymptomatic when reviewed at 3 months and a repeat angiogram revealed a healed dissection flap [Figure 2c].

DISCUSSION

We undertook a comprehensive review of the literature since it was first reported in 1931. We searched ‘Medline’ and ‘PubMed’ using the MESH headings ‘pregnancy-related myocardial infarction’, ‘pregnancy-related coronary artery dissection,’ and ‘spontaneous coronary artery dissection’ and ‘acute coronary syndrome in pregnancy’. A manual search of the bibliographies of all selected reports was then performed. Koul et al.,[7] in 2001, reported 58 cases of pregnancy-associated SCAD (p-SCAD) between 1952 and 1999. Appleby et al.,[18] in 2009, reported additional 25 cases of p-SCAD between 1999 and 2008. A total of 118 case reports have been published since 1952, including our two cases [Table 1].

Table 1

Pregnancy – related spontaneous coronary artery dissection

Our search revealed another 10 cases (case number 55, 56, 57, 58, 65, 70, 71, 72, 83, 117) between 1952 and 1999, which were not included by Koul et al.,[7] in their literature review [Table 1]. Between 1999 and 2008, there were additional 14 cases (case number 18, 19, 20, 21, 25, 29, 30, 31, 35, 37, 40, 42, 48, 49), which were not included by Appleby et al., in their review of the literature [Table 1]. Between 2008 and 2010, there were 10 case reports published.

The mean age at presentation was 32.62 years (youngest 22 years; oldest 44 years). The mean parity was 1.08. The earliest reported case was at first trimester and the latest was at 3 months postpartum. There were 92 (77%) postpartum reported cases (earliest 2 days postpartum; latest 3 month postpartum) and 27 (23%) cases during gestation (earliest 20 weeks pregnancy; latest 40 weeks gestation).

Pathogenesis

The pathogenesis of SCAD is unknown. The body undergoes different hormonal and hemodynamic changes during pregnancy and in the post-partum period; it may take upto six months after delivery for the body to achieve the pre-pregnancy status. Several theories have been postulated with regards to p-SCAD. It is suggested that the morphological changes in arterial wall associated with hemodynamic changes may be a contributory factor. Excess progesterone during pregnancy induces the loss of normal corrugation of elastic fibres and degeneration of medial wall collagen and all this may result in weakening of the arterial wall leading to arterial dissection. Heafner et al.,[19] suggested a two-step process leading to SCAD: an initial intimal rupture followed by delayed bleeding in tunica media likely caused by the clotting changes that occur in pregnancy. Bleeding from vasa vasorum into tunica media has been proposed as a possible cause of arterial dissection.[1220] Robinowitz et al., postulated an association with vasculitis and peri-adventitial infiltrates composed of eosinophilic lymphocytes or histiocytes.[21] Dowling et al.,[22] proposed that peri-adventitial inflammation were a consequence of SCAD and not the actual cause.

Cocaine abuse and the strenuous physical exercise have been suggested as possible causes.[23-26] Koul et al.,[7] postulated that the hemodynamic changes that occur during pregnancy may initiate the intimal tear and subsequent hemorrhage into the media of coronary artery.

Other factors such as use of oral contraceptives, immunosuppressant drugs, drug reactions, blunt trauma to chest,[27] type IV Ehlers Danlos syndrome[28] Marfan's syndrome,[29] and α1-antitrypsin deficiency[30] have also been described as possible mechanisms leading to arterial dissection.[31-34] Crystal medial necrosis has also been implicated in SCAD.[35]

How do patients present?

The most common presentation is acute coronary syndrome but the severity may range from unstable angina to acute myocardial infarction and cardiogenic shock. The disease is associated with high mortality about 50% at presentation.[12] Sudden death without evidence of myocardial infarction is much more frequent.[36] The mortality exceeds 70% for patients who present with myocardial infarction.[37] The survival rate is fairly good, about 85%, for patients who survive the acute phase.[38] Survival is possible in patients if luminal obstruction is incomplete or with myocardial infarction without serious complications.[39-42]

Risk factors

A review of the literature revealed that 76 (64%) did not have any risk factors; 7 (6%) had multiple risk factors, while risk factors in others included antiphospholipid 2 (1.68%), fibromuscular dysplasia 1 (0.84%), positive family history of ischemic heart disease 6 (5%), hypercholesterolemia 2 (1.68%), hypertension 7 (5.88%), smoking 11 (9%), oral contraceptives 1 (0.84%); risk factors were unknown in 6 (5%) cases. There is an increased risk of SCAD in patients with advancing age and multiparity.[43]

Diagnosis

There should be a high degree of suspicion of SCAD in any young peripartum or postpartum lady presenting with chest pain. If the index of suspicion of a cardiac ischemic event is high, despite any perceived lack of cardiac risk factors, urgent coronary angiography should be considered.[2344-46]

Angiographic Diagnosis

SCAD occurs in normal coronary vessels. The dissection can involve both right and left coronary arteries. Kemineni et al., reviewed 154 cases and reported that left anterior descending (LAD) artery was frequently involved in women (66% vs 41%) and right coronary artery (RCA) is commonly involved in men (50% vs 28%).[15]

A review of the published literature revealed that LAD was involved in 49 (41%) of cases and RCA in 13 (11%); 42 (35%) had multivessel dissection. Other vessels were less frequently involved: LMS 7 (6%), LCx 5 (4.2%), OM 1 (0.84), and no information was available in 2 (1.68%) cases.

Management

The guidelines for the optimal management of SCAD have yet to be established. The published data describes different management strategies including conservative treatment, percutaneous coronary intervention, coronary artery bypass grafting (CABG),[1-738] and heart transplantation.[1]

The factors that may influence the decision regarding the best treatment option include

Hemodynamic stability of the patient

Site of dissection

Number of vessels involved

Availability of coronary intervention services

Mortensen et al., in Western Denmark Heart Registry Study, mentioned that the location and the extent of the dissection guided their treatment strategy:

Lesions that involved LMS were treated with CABG

Proximal lesions of LAD, LCx and RCA were treated with PCI, and

Distal lesions were managed conservatively.[47]

Conservative Management

The conservative management may include use of heparin, beta blockers, calcium channel blockers, nitrates, diuretics, antiplatelet therapy including aspirin, clopidogrel, and glyprotein IIb/IIIa inhibitors.[4849]

The information regarding the safety of some of these drugs in pregnancy is limited. The drugs, which may be administered safely during pregnancy include unfractionated heparin or LMW heparin, aspirin, beta blockers, nitrates, morphine, and frusemide. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contra-indicated due to the risks to the fetus.[4750] Clopidogrel is not recommended during breast feeding; its safety in pregnancy is however unknown. The safety of glycoprotein IIb/IIIa inhibitors in pregnancy is not known.

Atay et al., suggested that patients who have completed an acute event or those with no evidence of ongoing ischemia and no significant stenosis on cardiac catheterisation may do well with conservative treatment in short term but most of these patients have had recurrent angina, subsequent myocardial infarction or sudden death due to extension of dissection.[51]

Thrombolysis

The use of thromboytics in pregnancy remains controversial. They may resolve the thrombus in the false lumen leading to improvement of the flow in the true lumen.[52] They may lead to further extension of the existing dissection by lysing a false lumen thrombus.[253] Pregnancy therefore remains a relative contraindication to thrombolytic therapy[48] and is best avoided in these circumstances. The literature review revealed that the thrombolytics were used in 9 (7.56%); 96 (86%) did not have any thrombolytics. No information was available in 14 (12%) cases.

Percutaneous coronary intervention

Percutaneous coronary intervention is the treatment of choice in SCAD with involvement of a single vessel with ongoing ischemia.[16] Whether Drug-Eluting Stents(DES) have any benefit over BMS in the setting of SCAD is not known and there have been no trials due to the rare occurrence of the condition.

Coronary Artery Bypass Grafting (CABG)

Paez et al., reported a case treated with revascularisation surgery, ventricular assistance and heart transplant.[54] CABG is the preferred mode of treatment in patients with Left Main Stem (LMS) dissection, multivessel dissection or complex lesions[317234455-57] or in patients with failed coronary intervention.[16]

Surgical myocardial revascularisation has been shown to achieve good results[565859] and is considered to be the first line treatment when multiple vessels are involved.[60] One of the major problems with CABG is that it is difficult to clearly identify the true lumen, which may result in grafting of the false lumen leading to irreversible myocardial damage or death.[16] Heart transplantation has been tried with success in cases of severe heart failure following a coronary artery dissection.[61]

Prognosis

The prognosis of patients with SCAD is poor. Benham et al., in their review of 123 cases reported death in 67% of patients, whilst 33% survived treated either conservatively or by surgery.[62] Jorgensen et al., reported 100% survival in a series of 10 consecutive patients who underwent surgical treatment.[12]

A review of the literature showed that 36 (30.25%) were treated medically; 25 (21%) had CABG, 25 (21%) had PCI, 3 (2.52%) had heart transplant, 1 (0.84%) had extrusion of hematoma, 2 (1.68%) had PCI and CABG, 24 (20.16%) did not have any treatment. Information was not available in 3 (2.52%) cases. Eighty-nine (75%) cases survived, whilst 25 (21%) died; no information was available in 5 (4.2%) cases.

The prognosis of SCAD has improved in the recent years. An overall mortality of 66% was reported by Engleman et al., in a retrospective study in 1993.[63] More recently, Koul et al., in 2001 reported a much lower mortality of 38%.[7] Last reported death because of SCAD was in 1998, according to the literature review.[7] First reported alive case was in 1978.[7] Between 1952 and 1999, out of 64 cases, 37 (58%) cases survived; 25 (39%) cases died. No information available in 2 (3%) cases. Between 1999 and 2010, out of 55 cases, there was no reported death. No information was available in 3 (5.4%) cases.

CONCLUSIONS

SCAD is a relatively common cause of acute myocardial infarction in young women who are pregnant or in the puerperium. A high index of suspicion is critically important when dealing with any young woman presenting with chest pain associated with pregnancy. A timely diagnosis of this fatal condition helps in deciding about the appropriate treatment and a successful outcome.