Spontaneous coronary artery dissection: an uncommon primary presenting feature of fibromuscular dysplasia

Abstract

Spontaneous coronary artery dissection is a rare but increasingly recognised cause of acute coronary syndrome particularly in young women, accounting for up to 25% of acute coronary syndrome cases in women under 50. It is, however, an uncommon primary presenting pathology of underlying fibromuscular dysplasia. We present the case of a woman in her 40s, with no significant medical history, presenting with anterior ST elevation myocardial infarction, identified as spontaneous coronary artery dissection on invasive coronary angiogram with an underlying aetiology, and subsequent diagnosis, of fibromuscular dysplasia being established on MR angiography.

Background

Spontaneous coronary artery dissection (SCAD) is a rare but important cause of acute coronary syndrome (ACS) thought to account for between 0.28% and 1.1% of all ACS cases.¹ It is triggered by the sudden disturbance of the arterial wall leading to intimal separation and intramural haematoma formation within the affected artery. This can then propagate along the length of the vessel leading to the development of a true lumen and false lumen. This false lumen can expand to such an extent that blood flow within the true lumen is impaired potentially resulting in myocardial ischaemia. It is a disease that primarily affects young patients, particularly women, with SCAD responsible for up to 25% of ACS cases in women under 50.² It is well recognised that SCAD is associated with the systemic arterial disease fibromuscular dysplasia (FMD), however, it is rare and unusual to be the primary presenting pathology in patients with this underlying condition.

We present the case of a women in her 40s, presenting with acute ST elevation myocardial infarction, identified as SCAD on invasive coronary angiography with an underlying diagnosis of FMD established on subsequent magnetic resonance angiography of renal vessels.

Case presentation

A woman in her 40s, with no significant medical history, presented to hospital via the primary percutaneous coronary intervention pathway after developing sudden-onset severe central chest pain at work, with no radiation or other associated symptoms of diaphoresis or shortness of breath. No previous symptoms of same noted in history. Initial ECG with ambulance service confirmed anterior ST elevation and she proceeded directly to the coronary catheterisation lab for invasive coronary angiography. On arrival to the lab, patient had ongoing chest pain but was haemodynamically stable with no evidence of arrhythmia on cardiac monitor nor any clinical signs of heart failure. In line with the primary percutaneous coronary intervention (PCI) service, the patient was loaded with aspirin 300 mg and ticagrelor 180 mg for suspected ST elevation myocardial infarction. Angiographic assessment of her coronary arteries showed no acute thrombus or vessel occlusion, however, there was abrupt lumen size change in the mid left anterior descending (LAD) artery with the mid and apical vessel appearing tortuous (figure 1). Angiographic appearance was classical of SCAD of the mid and apical LAD. Reassuringly, there was TIMI (Thrombolysis in Myocardial Infarction) 3 flow within the vessel and as haemodynamic stability was maintained throughout, the operator elected not to perform vessel instrumentation as the diagnosis was clear and it would not alter management. Left ventriculogram study showed apical wall hypokinesis with visually moderate left ventricular (LV) impairment. The patient was managed conservatively with no intervention required and was subsequently transferred to a local hospital the day after her angiogram for ongoing assessment and treatment. The operator noted that no cause of SCAD was evident from her clinical presentation or medical history.

Figure 1.

Invasive coronary angiogram angiographic image of the Left Anterior Descending (LAD) artery showing abrupt change in lumen size (red arrow) with the mid and apical vessel being tortuous and small in calibre (blue arrow) in keeping with spontaneous coronary artery dissection of the mid and apical LAD.

Investigations

Serum haematology/biochemistry results

• Initial troponin T 1954 ng/L—reference range <14 ng/L.

• Repeat troponin T 48 hours after invasive coronary angiogram 959 ng/L

• N-terminal Pro B-type Natriuretic Peptide (NT-pro-BNP) —237 ng/L—reference range <172 ng/L.

• Full blood count, C reactive protein, urea and electrolytes all normal.

Invasive coronary angiogram (figure 1).

• Coronary anatomy is right dominant.

• Right coronary artery is large and angiographically normal.

• Side-by-side origins of the Left Anterior Descending (LAD) and left circumflex.

• Left circumflex was non-dominant, but a reasonable calibre vessel and angiographically normal.

• LAD was angiographically normal up until the mid-vessel. At that point, there was an abrupt change in lumen size. The mid and apical vessel was tortuous and small in calibre with TIMI 3 flow. It was a classical angiogram of SCAD of the mid and apical LAD.

ECG—day 1 postinvasive coronary angiogram (figure 2).

Figure 2.

ECG day 1 post invasive coronary angiogram ECG showing sinus rhythm with mild T wave inversion in V1–V3, flattening V4–V6 with subtle inferior reciprocal ST depression.

• Sinus rhythm, HR73 beats per minute, PR interval 118 ms, QRS duration and morphology normal, QTc 414 ms, mild T wave inversion V1–3, T wave flattening V4–V6, subtle reciprocal horizontal ST depression 1 mm in inferior leads II, III and AVF

ECG—day 2 postinvasive coronary angiogram (figure 3).

Figure 3.

ECG day 2 post invasive coronary angiogram ECG showing more established T wave inversion V1–V6 with resolution of previous reciprocal inferior ST changes.

• Sinus rhythm, HR 65 beats per minute, PR interval 128 ms, QRS duration and morphology normal, QTc 444 ms, more pronounced and established T wave inversion V1–V6, previous reciprocal inferior ST depression resolution.

ECHO

• Left ventricle: Global systolic function: mild-moderately impaired LV ejection fraction. The ejection fraction is estimated between 40% and 45% and by Simpson’s biplane method is 42%.

• Regional systolic function: Apical anterior: akinetic. Apical lateral: akinetic. Apical inferior: akinetic. Apical septal: akinetic. Apex: akinetic.

• LV cavity size and wall thickness normal.

• Right ventricle: Normal cavity size and systolic function.

• Mild tricuspid regurgitation—low probability of pulmonary hypertension. TR Vmax 2.2 m/s.

Magnetic Resonance Angiography (MRA) thoracic aorta—completed as outpatient (figures 4–6).

Figure 4.

MR angiogram of thoracic aorta Image showing beading and irregularity of the distal third of right renal artery (red arrow) with reduced vessel calibre (blue arrow) versus the left renal artery which is of normal calibre (green arrow).

Figure 5.

MR angiogram of thoracic aorta three dimensional reconstruction image with anterolateral projection highlighting the beading (blue arrow) and stricturing (red arrow) of the distal right renal artery in keeping with fibromuscular dysplasia. Reduced vessel calibre is also present (green arrow).

Figure 6.

MR angiogram of thoracic aorta three-dimensional reconstruction image with posterior projection highlighting the beading of the distal right renal artery (white arrows) in keeping with fibromuscular dysplasia.

• Normal calibre aortic root, arch descending thoracic and abdominal aorta. No aneurysm or dissection.

• Origins of the great vessels are unremarkable with a standard arrangement.

• Coeliac, superior mesenteric and single bilateral renal artery origins are patent. Satisfactory aortic bifurcation. No evidence of large vessel vasculitis.

• The right renal artery is of generally small calibre, there is beading and stricturing in the distal segment just proximal to the hilum, with a further potential stenosis/web just distal to the ostium.

• The left renal is of good calibre, no definite stricturing or beading seen here. No microaneurysm formation.

• Remainder of the visceral arteries outline normally. Within limitations of the sequences obtained the visualised portions of the liver, spleen, kidneys pancreas and adrenals are unremarkable.

• Simple appearing cortical cyst mid-pole right kidney. Lung bases are clear. No central pulmonary embolism.

• Conclusion: Beading and irregularity of the distal third of right renal artery is strongly suspicious for FMD.

Differential diagnosis

Given symptoms of chest pain with dynamic ECG changes, ACS was suspected but excluded with the use in invasive coronary angiography with a diagnosis of SCAD being established during her angiogram. Moderate LV impairment was visualised via LV ventriculogram study and confirmed on subsequent echocardiogram.

Treatment

In the absence of acute vessel thrombosis or occlusion and the fact TIMI 3 flow was evident within the left anterior descending artery, the patient was managed conservatively with no instrumentation or invasive intervention to the affected vessel required. Echocardiogram conducted following her angiogram showed mild to moderate LV impairment with regional wall abnormalities. Following transfer to a local cardiology unit, serial ECGs taken in the days following her angiogram showed increasingly established T wave inversion in her anterior leads (figures 2 and 3). The patient was started on aspirin 75 mg once a day, bisoprolol 2.5 mg once a day, atorvastatin 40 mg once a day and ramipril 2.5 mg once a day for both secondary risk reduction and treatment of LV impairment and was discharged 5 days after her initial presentation.

Outcome and follow up

On discharge, the patient was enrolled in a 4-month cardiac rehabilitation programme. She was also referred to the heart failure service in her local hospital that reviewed symptoms and attempted uptitration of meds, however, due to blood pressure of 90/60 and heart rate of 60 BPM, the patient was considered medically optimised and discharged from their care. Outpatient investigations were requested on discharge in the form of MR angiography of renal and carotid arteries and thoracic aorta to investigate possible aetiologies of SCAD. The MRA assessment of her renal arteries and thoracic aorta were conducted 4 weeks following discharge. This showed beading and irregularity of the distal third of right renal artery strongly suspicious of FMD (figures 4–6). Following these results, the patient was subsequently referred to interventional radiology for consideration of renal artery intervention.

Discussion

SCAD is an uncommon but important cause of ACS accounting for between 0.28% and 1.1% of all ACS cases,¹ however, incidence is thought to be higher.² It is a disease process that primarily affects young patients,³ particularly women who account for up to 70% of cases.^{4 5}

SCAD occurs when an intramural haematoma forms between the layers of the affected arterial wall. This can occur as result of intimal tear and flap formation giving ingress of blood between the tunica intima and tunica media or between the tunica media and tunica adventia. Another proposed mechanism is thought to arise from rupture to of the vaso vasorum allowing for the development of an intramural haematoma without intimal lining disruption.⁶ Irrespective of the mechanism of injury, the intramural haematoma gives rise to a false lumen, which can propagate along the length of the vessel. Should significant stenosis of the true lumen occur as a result, blood flow disruption can lead to myocardial ischaemia. The right coronary artery is the most common site of SCAD in men while the left anterior descending artery is the more common site in women.⁷

While SCAD can develop as a result of pre-existing atherosclerotic disease, the degree of dissection propagation is generally more limited as a result of atrophy and vessel calcification. In contrast, non-atherosclerotic SCAD is associated with greater dissection propagation and a wide variety of predisposing factors such as FMD, multiple pregnancy, systemic inflammatory conditions such as inflammatory bowel disease, sarcoidosis, polyarteritis nodosa, systemic lupus erythematosus, connective tissue disorders such as Marfan’s syndrome or Ehler-Danlos and coronary artery spasm. Medications such as hormonal therapy, or use of sympathomimetic drugs, for example, cocaine, amphetamines, methamphetamines can also contribute to development of SCAD.⁸ Ultimately, the predisposing factors to non-atherosclerotic SCAD increase the probability of arterial bed damage.

One of the most well-recognised risk factors for SCAD is FMD, a non-atherosclerotic, non-inflammatory arteriopathy that can lead to stenosis, aneurysm, dissection or occlusion of affected vessels.⁹ While the underlying aetiology is not fully understood, it is thought to be a multifactorial disease with gender/hormonal, genetic and environmental influences. This disease is most commonly seen in patients under 50, however, it can present across a patient’s lifespan. It also primarily affects women who account for up to 90% of FMD cases.¹⁰

FMD can be classified histologically depending on the vessel wall layer affected and angiographically depending on the visualised vessel disturbance.

Histology classification is:

• Medial: 90%–95%.

  • Medial dysplasia (70%, the most common type).

  • Perimedial (subadventitial) fibroplasia (15%–20%).

  • Medial hyperplasia (8%–10%).

• Intimal 5%

  • Intimal fibroplasia.

• Adventitial: rare.

  • Adventitial fibroplasia (1%).

Angiographic classification is described as either focal or multifocal. Multifocal FMD is the classic ‘string of beads’ appearance on angiography due to alternating dilatation and constriction of the vessel. Focal FMD is seen as concentric or tubular stenosis.¹¹

Clinical presentations of FMD are typically reflective of the affected arterial beds. Renal, external carotid and vertebral arteries are the most commonly affected vessels, however, any arterial bed can be impacted. In renal FMD, renovascular hypertension is the most common presentation,¹² which is often resistant to medical therapies. It can, however, also be associated with hypokalaemia from secondary hyperaldosteronism, flank pain, renal artery dissection and ischaemic nephropathy with renal failure however this is rare.

If renal FMD is identified, craniocervical FMD should be excluded due to the risk cerebrovascular events. Patients with craniocervical FMD are often asymptomatic, however, headache is the most common symptom of FMD outside of hypertension. Pulsatile tinnitus, neck pain and dizziness are also seen, however, Horner’s syndrome, subarachnoid haemorrhage, Transient Ischaemic Attack (TIA) and stroke are some of the most serious and feared complications of craniocervical FMD.¹³

Coronary artery manifestations of FMD can be a diagnostic challenge as the ‘string of beads’ appearance is uncommon in coronary FMD. The most common angiographic findings are arterial tortuosity with most patients having at least a mild degree present. Distal tapering of the coronary artery and irregular focal stenosis unrelated to atherosclerosis can also be seen.¹⁴ These abnormalities, however, are not always readily visible with traditional angiographic assessment. Additional imaging modalities in the form of intravascular ultrasound (IVUS) or optical coherence tomography (OCT) can be used. These technologies provide supplementary tomographic information of the affected vessel potentially identifying some of these abnormalities that might otherwise be missed.¹⁵

In the setting of SCAD, these techniques allow visualisation of the different layers of the coronary vessel, confirmation of an intramural haematoma, evaluating the degree of true lumen compression and assessing circumferential and longitudinal extension of the lesion. They also play an important role in guiding management if intervention is being considered

Most patients with SCAD related to FMD are managed conservatively with standard ACS therapies in the form of antiplatelet and beta blocker agents to modify shear forces across affected arterial segments.¹⁶ Due to the underlying arteriopathy, instrumentation of the affected vessel is avoided where possible owing to increased risk of complications.¹⁷ In cases where SCAD is clearly evident on standard angiographic assessment and conservative management is appropriate, as in TIMI3 flow is present in the affected artery and haemodynamic stability is maintained, current guidelines do not recommend vessel instrumentation.¹⁸ If, however, there is warrant for vessel intervention or where diagnostic ambiguity is present, careful instrumentation of the vessel can be performed with the use of intracoronary imaging techniques providing valuable information in guiding treatment strategies. In haemodynamically unstable patients or where dissection is causing significant vessel stenosis, invasive interventions such as Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Graft (CABG) can be considered on a case-by-case basis¹⁹ with the former warranting the use of IVUS and/or OCT to guide stent deployment.²⁰

When it comes to SCAD related to FMD, the literature does not have a unified approach to the management of such patients given the complexity of invasive intervention and risk of complications. While the majority of patients have resolution of their dissection on subsequent angiographic follow-up,²¹ patients with SCAD related to FMD have worse long-term outcomes compared with patients with non-FMD related SCAD with higher rates of recurrent myocardial infarction, recurrent SCAD, revascularisation and major adverse cardiovascular events.²²

While the association between SCAD and FMD is well established, it is unusual for a patient to present with SCAD as the primary pathology related to FMD. As stated, renal and carotid/cervical arteries are more commonly affected. In this case, the patient had no symptoms associated with FMD in these areas and was in fact somewhat hypotensive even with FMD identified in her right renal artery. Indeed, the degree of hypotension was so pronounced that heart failure therapies had to be withdrawn due to symptomatic hypotension. Additionally, renal function was normal though renal failure due to FMD is rare.²³ Furthermore, the patient reported no neurological symptoms suggestive of carotid or cervical vessel involvement though imaging of these areas is outstanding at time of publication. While the incidence of SCAD is higher in patients with FMD, the prevalence of patients presenting with SCAD as the sole feature of underlying FMD with no other clinical symptoms is uncommon. Although the use of intracoronary imaging techniques such as IVUS or OCT may have identified coronary FMD features at the time of her angiogram, current clinical recommendations do not support the instrumentation of vessels affected by SCAD where TIMI3 flow is evident, haemodynamic stability is maintained and a conservative approach is appropriate²⁴ as was the case here.

This case highlights that FMD should be considered as an underlying aetiology in young women presenting with ACS due SCAD. It has been demonstrated that a significant proportion of SCAD patients have underlying FMD²⁵ even when signs or symptoms of wider systemic arterial involvement are not evident. Early vascular screening for arteriopathy is essential in obtaining an underlying diagnosis and given the rate of recurrent events in this population, long-term follow-up is essential.

Learning points.

• Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognised cause of acute coronary syndrome in young women.

• Fibromuscular dysplasia (FMD) should be considered as an underlying aetiology in young women presenting with SCAD.

• Timely vascular screening is essential in establishing a diagnosis of FMD and identifying the extent of vascular beds affected.

• In haemodynamically stable patients with SCAD due to FMD, management is largely conservative with antiplatelet and beta blocker therapies being the mainstay therapies used.

• Invasive intervention such as PCI or CABG is an uncommon treatment strategy but can be considered in high risk or haemodynamically unstable patients on a case-by-case basis with the use of intracoronary imaging techniques such as IVUS or OCT guiding management.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).