Takotsubo syndrome unmasking malignant coronary artery anomaly in a patient presenting with acute coronary syndrome: Expanding definitions of Takotsubo cardiomyopathy?
- 1 Medical student, College of Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
- 2 Science student, College of Arts and Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
- 3 Cardiology, University of Saskatchewan College of Medicine, Saskatoon, Saskatchewan, Canada
- Correspondence to Dr Shravan Nosib; shravan.nosib@gmail.com
Abstract
The simultaneous occurrence of Takotsubo syndrome, congenital coronary artery anomaly and severe coronary artery disease is a rare clinical triad. This case report highlights the intricacies of management of this ‘triple jeopardy’ scenario.
Background
Takotsubo syndrome (TTS) is a relatively new diagnostic consideration in patients presenting with an acute chest pain syndrome. Diagnostic criteria for TTS continues to evolve from the simplistic chest pain syndrome, acute left ventricular (LV) dysfunction and normal coronaries.
We present a patient with TTS, atheroslerotic coronary artery disease and abnormal origin of the right coronary artery (RCA) from the left sinus of Valsalva. We outline the management of this potentially lethal coronary artery anomaly (CAA) in this peculiar scenario.
Case presentation
A 66-year-old woman with a medical history of hypertension, dyslipidaemia and rheumatoid arthritis presented to the local emergency room with chest pain suggestive of acute coronary syndrome (ACS). She had been under significant stress prior to her symptoms with the recent loss of her mother as well as her husband’s diagnosis of terminal cancer.
On examination, blood pressure was 153/83 mm Hg, heart rate was 104 bpm regular, and oxygen saturation was 96% on room air. Cardiovascular examination was unremarkable. ECG showed normal sinus rhythm with prominent generalised T wave inversions suggestive of ACS (figure 1). Corrected QT interval was prolonged at 592 ms. Biomarkers were positive for ACS. High sensitivity troponins peaked at 248 ng/L, CK was mildly elevated 473 IU/L. Brain natriuretic peptide (BNP) was elevated at 1053 ng/L. Intravenous metoprolol 10 mg was administered slowly resulting in sinus bradycardia with heart rate of 50–60 bpm.
12-lead ECG showing generalised deep T-wave inversions and prolonged QT-interval of 642 ms. PR, time to atrial activation; QRS, axis of the heart; QRSD, time to ventricular activation; RR, time interval between 2 beats.
Investigations
The patient was directed to emergent cardiac catheterisation because of ongoing chest pain. The left coronary system was normal, the dominant RCA arose from the left coronary sinus and ran intramurally through the aortic wall in its proximal portion for about 12 mm (video 1). There was a 70%–80% atherosclerotic plaque in the proximal portion of the RCA with no evidence of plaque rupture. LV angiography demonstrated apical ballooning and basal hypercontractility in keeping with a diagnosis of TTS (video 2). Acute LV end-diastolic pressure was elevated at 25 mm Hg. LV ejection fraction (EF) was estimated at 25%–30%. Attempts to study the plaque with intravascular ultrasound (IVUS) was unsuccessful due to technical reasons. No interventions were performed and the patient was admitted to the coronary care unit for further workup. She responded well to anticoagulant therapy with heparin, aspirin and clopidogrel. She was also started on low-dose metoprolol 12.5 mg by mouth two times per day. In hospital, she developed paroxysmal atrial fibrillation. Sinus rhythm was restored with intravenous metoprolol.
Differential diagnosis
All working diagnoses need to be substantiated.
Treatment
These findings were discussed with the patient along with potential complications including risk of sudden cardiac death (SCD) and myocardial infarction. The patient agreed to undergo outpatient elective surgery.
During the surgery, the RCA was ligated at its origin and transected after unsuccessful attempt to unroof the intramural segment. It was then reimplanted in the right coronary sinus after osteoplasty. Postoperatively, the patient had an uncomplicated course in the ICU except for two bouts of paroxysmal atrial fibrillation. She was restored to sinus rhythm with sotalol and was discharged home on ASA 81 mg daily, sotalol 40 mg two times per day, ramipril 5 mg daily, atorvastatin 40 mg daily and warfarin as per international normalised ratio (INR).
Outcome and follow-up
Follow-up echocardiogram has documented normal LV systolic function with EF of 55%–60%. There was a small area of scarring in the inferoseptal segment. She has excellent aerobic capacity and subsequent outpatient stress test was clinically and electrically negative at high workload.
Discussion
This case highlights a unique triad of typical TTS in a patient with an abnormal RCA origin as well as significant proximal RCA disease. This clinical scenario begs the pertinent question of whether the congenital CAA was the cause of the TTS or an innocent bystander. Unfortunately, there are very few case reports of CAAs and TTS to shed light on this triple jeopardy scenario.
CAAs are rare with an incidence of about 1%, but may be associated with life-threatening complications, namely myocardial infarction and arrhythmic SCD, particularly after exertion.1 2
The interarterial course of the RCA between the aorta and the pulmonary artery is associated with an adverse prognosis.3 They may cause myocardial ischaemia due to coronary spasm at the tunelled segment and by systolic compression of the anomalous RCA by the aorta and pulmonary infundibulum. IVUS imaging has recently demonstrated the presence of intramural proximal intussusception of the ectopic artery at the aortic root wall.4 Angelini et al describe the following mechanisms of stenosis and ischaemia in these patients, namely (1) coronary hypoplasia since arteries that arise inside the aortic media cannot grow normally; IVUS has shown that the intramural intussuscepted segment of the proximal ectopic artery is smaller than the more distal extramural artery and a hypoplasia index has been proposed to stratify these patients;4 5 (2) lateral compression of the intramural segment of the ectopic artery increases with exertion and (3) stenotic segment length (between 5 and 12 mm).4 5
High-risk features of CAAs include a slit-like ostium, acute take-off angle, and inter-arterial or intramural course.6 We suggest the inclusion of TTS as a high risk presenting feature as this is known to be associated with SCD.1 2
In our case, the patient experienced several emotional stressors prior to onset of TTS symptoms. The ‘catecholamine storm’ in TTS also increases heart rate and stroke volume and consequently increases the diameter of the aorta and pulmonary trunk, resulting in further compression of the aberrant RCA in its interarterial (aorta and pulmonary artery) and intra-arterial (intramural aortic course) course. This dynamic compression would have been more accentuated in the presence of already existing stenosis in that segment. The dynamic interplay of these haemodynamic factors, driven by TTS, may have added an ischaemic insult to the inferior LV wall, a finding supported by the fact that the inferior LV wall showed more marked regional wall motion abnormality (RWMA) than the other walls as well as scarring on cardiac MRI. We do not believe that the unruptured atherosclerotic RCA plaque was the initiating event in the patient’s clinical presentation as an ACS, but was rather secondary to the sympatho-adrenergic stimulation of TTS.
The diagnostic waters are muddied by the fact that the diagnostic criteria for TTS do not mention congenital heart disease, while being inclusive of significant coronary artery disease.7 The expert consensus document on TTS, while emphasising the extensive RWMA beyond a single epicardial arterial distribution as a sine qua non for considering a diagnosis of TTS, is also careful to mention that in rare cases focal TTS may present as RWMA in the territory supplied by a single coronary artery.7
Thus as a general guiding principle, one has to demonstrate a perfusion-contraction mismatch to distinguish RWMA due to TTS from ischaemia or infarction.The LV angiogram of our patient demonstrated that extensive RWMA(video 1).
The InterTAK diagnostic criteria provides a diagnostic platform to assess the likelihood of TTS.7 It is a scoring system comprising seven parameters, namely: female sex (25 points), emotional trigger (24 points), physical trigger (13 points), absence of ST segment depression (12 points), psychiatric disorders (11 points), neurological disorders (9 points) and QT prolongation (6 points). These are rank based on their diagnostic import, with a maximum score of 100 points. Patients with a score greater than 70 points have a diagnostic probability of almost 100%. The beauty of these criteria lies in their simplicity, they can be easily obtained in the emergency room and exclude the need for a diagnostic imaging modality. Our patient scored 80 points on these criteria (female, emotional triggers, physical triggers, absence of ST depression and QT prolongation) with a TTS probability of 100%. The diagnosis of TTS was verified using the revised Mayo Clinic criteria, the more widely accepted diagnostic criteria. All proposed criteria for diagnosis of TTS have only one element in common, namely the fact that TTS is still a diagnosis of exclusion. There is no single diagnostic test that would qualify as the gold standard. However, the diagnostic criteria for TTS fall short when it comes to the ‘locus standi’ of congenital heart disease, the step-child of adult cardiology.
SCD, after extreme exertion, in patients with CAAs (in the absence of other potentially fatal conditions) is preceded by low cardiac output, bradycardia, asystole and syncope. Terminal ventricular fibrillation may be secondary to critical ischaemia or of reperfusion arrhythmia.8–10 Other clinical manifestations include atypical chest pain syndrome, palpitations, angina pectoris, dizziness and syncope. It is interesting to note that while SCD is associated with unusual exertion in young adults, the non-lethal manifestations are more frequently seen in older adults, specifically women, and are related to the development of hypertension.11 Progressive hardening of the aortic walls in adults may have a protective effect against SCD.11
The management of CAAs in the setting of TTS presents a unique challenge as the clinician is faced with two potential causes of SCD simultaneously. Medical therapy with beta-blockers, ACE inhibitors and restriction of physical activity remain the cornerstone of therapy in the acute stage until the TTS has resolved. Percutaneous intervention of the obstructed proximal intramural segment of a patient with right CAA is technically challenging but feasible. Indications for stenting include (1) high risk of SCD, (2) luminal area stenosis greater than 50% with respect to distal normal vessel on IVUS, (3) large area of myocardium at risk and (4) evidence of reversible ischaemia.4 12 Restenosis with IVUS-guided drug-eluting stents appears to be rare based on limited available data and is related to in-stent fibrocellular proliferation, not dynamic stent compression.5
Surgical management, as per above indications, consist of (1) direct reimplantation of the ectopic coronary artery at the aortic root, (2) unroofing of the intramural coronary segment from the ostium to the exit point, off the aortic wall (attempted but unsuccessful in our patient) or (3) osteoplasty, which creates a new ostium at the end of the ectopic artery’s intramural segment, as performed in our patient.5 13–16
The nascent bond between TTS, CAAs and ACS is in full blossom. These conditions may cohabit and are not mutually exclusive; although an unlikely trio as described in our case report. Diagnostic criteria for TTS, currently one of exclusion, are called to evolve. Congenital heart disease beckons!
In conclusion, we believe that the severe sustained stresses experienced by our patient provoked acute stress-induced cardiomyopathy, TTS, which in turn precipitated a secondary ACS (type 2 MI) through the mechanisms described above and unmasked a potentially malignant CAA in the process—a blessing in disguise for our patient.
Learning points
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Coronary artery anomalies (CAAs) are generally clinically quiescent, but may present with acute arrhythmic life-threatening events or sudden cardiac death.
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The adult congenital cardiac population may represent a unique group perhaps more prone to Takotsubo syndrome (TTS), and under-reporting in this patient population may account for the very few cases documented in the literature. TTS may unmask a potentially malignant CAA.
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Percutaneous interventional therapies and surgical correction of CAAs require a careful selection of patients who are at high risk of life-threatening events to prevent sudden cardiac death.
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Diagnostic criteria for TTS need to address the status of congenital heart disease, an important cause of heart failure in the adult population.
Footnotes
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Contributors DK has written the clinical presentation and investigations sections of the case report. SN has written the management section and was responsible for citing the references. He also finalised the manuscript for submission. SN wrote the discussion and corrected the whole manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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