Treatment of left main coronary artery compression in the setting of unpalliated congenital heart a case series

Authors: Rahul Goli, Lina Ya’Qoub, David Blusztein, Vaikom S Mahadevan

Abstract

Background

Left main coronary artery compression syndrome (LMCS) is a well-characterized phenomenon resulting from compression of the left main coronary artery (LMCA) between the aorta and an enlarged pulmonary arterial trunk. The development of LMCS is usually described in the context of severe pulmonary arterial hypertension. Cases of LMCS, in the context of unpalliated congenital heart disease (CHD), are complex clinical scenarios that challenge traditional treatment paradigms.

Case summary

Here, we discuss two thought-provoking patients with unpalliated CHD complicated by severe pulmonary hypertension (PH). Both patients developed LMCS, one with severe non-ST elevation myocardial infarction and the other with refractory angina. Their pulmonary vascular resistance was severely elevated despite pulmonary vasodilator therapy, and concomitant surgical correction of their CHD in addition to bypass grafting was deemed high risk. They underwent successful percutaneous coronary intervention (PCI) of the LMCA with drug-eluting stents.

Discussion

Pulmonary hypertension can develop in the setting of long-standing unpalliated CHD. Surgical correction of congenital heart defects may be performed in select patients with systemic-to-pulmonary shunts, contingent on the status of PH severity. Pulmonary vasodilator therapy modulates haemodynamics to ensure surgical correction without risk of cardiopulmonary demise—termed the ‘treat and repair’ strategy. LMCS, an increasingly recognized phenomenon in patients with long-standing PH, is a notable complicating factor in the ‘treat and repair’ strategy. We introduce the concept that PCI of the LMCA may bridge patients to corrective surgery for CHD by allowing time for optimization of their pulmonary vasodilator therapy.

Introduction

Patients with unpalliated complex congenital heart disease (CHD) can develop pulmonary hypertension (PH) with severely enlarged pulmonary arterial trunks. The pulmonary artery (PA) can impinge on neighbouring thoracic structures most critically the left main coronary artery (LMCA).^1^ Left main coronary artery compression syndrome (LMCS) is associated with anginal symptoms, myocardial infarction, and even sudden cardiac death.^1,2,3^ Management of LMCS is more straightforward in the context of idiopathic World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH); in contrast, LMCS associated with PAH–CHD is a particularly challenging situation due to the need for surgical repair and high operative risk. Here, we describe two cases of LMCS arising in the setting of unpalliated CHD and treatment with percutaneous coronary intervention (PCI).

Timeline

Patient 1

The first patient is a 34-year-old woman of Mexican origin with unrepaired total anomalous pulmonary venous return (TAPVR) draining to the coronary sinus with concomitant large secundum atrial septal defect (ASD) resulting in common atrial physiology. From early childhood, she had a history of debilitating dyspnoea that had been attributed to asthma. She first learned of her congenital heart anomaly after becoming pregnant in her mid-20s and incredibly delivered a healthy newborn at term without complications. In her early 30s, she moved to USA as an asylum seeker.

During a primary care appointment, she was discovered to be hypoxic to an oxygen saturation of 89% on room air with complaints of chest discomfort and was admitted to a nearby hospital. There, her echocardiogram demonstrated a large ASD associated with right-sided chamber enlargement, right ventricular dysfunction, and normal left ventricular function with a left ventricular ejection fraction (LVEF) of 65%. Further investigation with right heart catheterization (RHC) showed a significantly elevated PA pressure (PAP) of 115/40 mmHg with a mean PAP (mPAP) of 65 mmHg, mean pulmonary capillary wedge pressure (PCWP) of 15 mmHg, a cardiac output (CO) of 2.52 L/min, and a pulmonary vascular resistance (PVR) of 19.8 Wood units (WU) consistent with severe pre-capillary PH. There was an increase in oxygen saturations between the inferior vena cava and superior vena cava (SVC) and the right atrium suggesting left to right shunting of blood flow at this level. Diagnostic testing was negative for chronic thromboembolic PH based on a negative ventilation/perfusion (V/Q) scan, obviating the need for antithrombotic therapy. Computed tomography (CT) scan during the admission demonstrated marked enlargement of the pulmonary arteries, measuring 5.5 cm in diameter. She was discharged on tadalafil, furosemide, and lisinopril with follow-up in PH clinic. She was concluded to have PAH–CHD falling under WHO Group I classification. In PH clinic, she was started on inhaled treprostinil. Repeat RHC about 6 months later showed reduced mPAP of 45 mmHg, improved PVR now measuring 10.5 WU, and an increased CO of 4.1 L/min. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 2.2 indicating continued left to right shunt while on pulmonary vasodilator therapy.

A year after her initial presentation, she had an admission to a local hospital for acute onset of periumbilical pain, subsequently diagnosed with pelvic inflammatory disease. While being treated with intravenous (i.v.) antibiotic therapy, she developed crushing chest pain with dynamic lateral ST depressions on serial electrocardiograms (EKGs). Her troponin I level markedly rose eventually reaching a peak value of 61 ng/mL (normal range 0.00–0.04 µg/L). An urgent coronary angiogram showed a 90% slit-like ostial narrowing of the LMCA suspected to be related to compression from adjacent thoracic structures. Given lack of acute plaque rupture, no intervention was performed. A confirmatory chest CT angiogram demonstrated a massively dilated PA compressing the LMCA ostium (Figure 1). Her course was complicated by hypoxic respiratory failure from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During treatment, she suffered three episodes of haemoptysis, eventually necessitating intubation. She deteriorated into cardiopulmonary failure requiring inotropic support, inhaled nitric oxide, i.v. treprostinil, and stress dose steroids.

Fortuitously, she was able to be stabilized after a month of critical care and was transferred to our centre for optimization of her PH therapy, treatment of LMCS, and consideration of repair of her CHD. On initial examination, she required 4 L of oxygen delivery to maintain an oxygen saturation of 100% and had a heart rate and blood pressure within normal limits. Physical examination was remarkable for a right ventricular heave and fixed splitting S2 heart sound with a loud P2 component. Additionally, there were both systolic and diastolic murmurs heard on the left sternal border. She had a cardiac magnetic resonance imaging (MRI) which showed thinning and transmural late gadolinium enhancement involving the basal to mid-interventricular septum with severe hypokinesis. Despite escalation of her pulmonary vasodilator therapy with the addition of ambrisentan and increased dose of i.v. treprostinil, a RHC showed severe mixed pre- and post-capillary PH with a mPAP of 52 mmHg, PVR of 4.3 WU, PCWP of 20 mmHg, and an absolute Qp of 9.17 L/min. After multidisciplinary discussion, corrective cardiac surgery was deemed high risk given severely elevated PAPs and PVR.

To allow time for further reduction of pulmonary pressure and enable safer conditions for corrective cardiac surgery, a multidisciplinary decision was made to proceed with PCI of the LMCA. Angiography redemonstrated severe compression of LMCA with 95% ostial stenosis and otherwise normal left coronary arteries with TIMI 3 flow (Figure 2A, see Supplementary material online, Video S1). The large calibre LMCA measured 4.6 cm by quantitative coronary analysis (Figure 2B). There was significant dampening of catheter pressure tracing on LMCA engagement; thus, to avoid the risks of total LMCA occlusion with intracoronary imaging, a direct stenting approach was taken. Upfront deployment of a 4.5 mm × 12 mm drug-eluting stent (DES) was followed by post-dilation with a 4.5 mm × 8 mm Flash Ostial balloon and then a final high-pressure inflation with a 5.0 mm non-compliant balloon (Figure 2C, see Supplementary material online, Video S2). Final intravascular ultrasound (IVUS) assessment demonstrated a well-apposed stent. Systolic blood pressures improved by approximately 40 mmHg post-PCI. Given resolution of her haemoptysis without acute source of bleeding by bronchoscopy and CT scan, we ultimately opted for treatment with DES to reduce risk of restenosis although consideration had been given to the use of a bare-metal stent. Long-term maintenance of stent patency was imperative given her young age.

She was discharged in stable condition on eplerenone, tadalafil, ambrisentan, and i.v. treprostinil. She is planned for surgical repair of her ASD with a fenestrated atrial septation and rerouting of the pulmonary veins to the left atrium. Repeat RHC at the 1-year follow-up showed significantly improved PH with mPAP of 36 mmHg and a PVR of 2.2 WU.

Patient 2

The second patient is a 22-year-old female with sinus venosus ASD and partial anomalous pulmonary venous return (PAPVR) with the right upper pulmonary vein draining into the junction of the SVC and right atrium. She was referred to our clinic for ASD closure due to symptoms of exertional dyspnoea and lightheadedness. Her vital signs were within normal limits. On physical examination, she had a right ventricular heave and a grade II systolic murmur best heard at the left sternal border. She denied drug use history. She had an echocardiogram that demonstrated a normal left ventricular function with an LVEF of 65%, a moderately increased right ventricular volume with mildly decreased function, and, of note, a right-sided pulmonary vein draining into the right atrium. A RHC demonstrated mPAP of 48 mmHg and a PVR of 4.6 WU along with a step up in oximetry between the vena cava and the right atrium. Her Qp/Qs was greater than 3. A CT chest was performed demonstrating an enlarged PA diameter measuring 4.0 cm in diameter in comparison to an ascending aortic diameter of 2.3 cm. She was started on pulmonary vasodilator therapy with tadalafil and ambrisentan.

At the 1-year follow up, she had newly developed exertional substernal chest pressure and was scheduled for right and left heart catheterization. She was found to have ostial LMCA compression but otherwise normal coronary arteries (Figures 3, see Supplementary material online, Videos S3–S4). LMCS was confirmed on CT scan (Figure 4). Her RHC on maximal doses of tadalafil, ambrisentan, and selexipag showed continued severe pre-capillary PH with a mPAP of 46 mmHg and a PVR of 4 WU. She was admitted to the hospital where she was started on i.v. prostacyclin therapy for continued moderate to severe PH. She had episodic anginal episodes with dynamic EKG changes but troponin I levels within normal limits. Given poor candidacy for near-term surgical correction of congenital heart defect and escalating anginal symptoms at rest, the decision was made to proceed with PCI.

An IVUS catheter showed dynamic compression of the proximal LMCA; however, the minimal luminal area was unable to be properly assessed due to echo dropout. Use of optical coherence tomography (OCT) better delineated the severity of the LMCA compression with a minimum lumen area of ∼4.55 cm^2^ (Figures 5A and B). A 4.0 mm × 16 mm DES was deployed, and subsequent angiography showed a well-positioned stent with TIMI 3 flow. There was an immediate ∼25 mmHg increase in systolic blood pressure. OCT was repeated with confirmation of a well-sized and expanded stent without evidence of vessel injury (Figure 5).

After 1 year, she had a follow-up cardiac catheterization demonstrating a patent LMCA stent. RHC demonstrated persistent pre-capillary PH with a mPAP of 59 mmHg and a PVR of 5.0 WU while on ambrisentan, tadalafil, sildenafil, digoxin, and i.v. epoprostenol therapy. After extensive discussion between the paediatric surgery and adult congenital cardiology team, decision was made to proceed with surgical repair. She had a successful PAPVR repair with baffling of the right upper and middle pulmonary veins through the sinus venosus ASD into the left atrium with a 5 mm fenestration. At the 1-year follow up, she was doing well with improvement in her pulmonary pressures on follow-up RHC and decrease in right ventricle (RV) size. She was successfully weaned from i.v. epoprostenol therapy with stable pulmonary pressures and right heart function.

Discussion

Pulmonary hypertension is a frequent complication of CHD occurring in 3–10% of adult cases. According to the new European Society of Cardiology (ESC) guidelines, PH is now defined as a mPAP > 20 mmHg and PAH is defined by a PVR > 2 WU as well as a PCWP < 15 mmHg.^4^ PAH–CHD is thought to develop due to unrestricted volume or pressure load on the pulmonary circulation, leading to adverse pulmonary vascular remodelling with resultant increased PVR. Eisenmenger syndrome (ES) is an extreme form of PAH–CHD with reversal of pre-existing large systemic-to-pulmonary shunts. Defect closure in ES is contraindicated as the shunt can maintain systemic circulation despite cyanosis.^5^ A second subgroup are those that have PAH associated with prevalent systemic-to-pulmonary shunts where cyanosis at rest is not present. Shunt closure may be beneficial depending on haemodynamic parameters.^4,5^ The 2018 ACC/AHA guidelines on Management of Adults with Congenital Heart Disease recommend against the closure of ASDs, ventricular septal defects (VSDs), and patent ductus arteriosus (PDA) in adults with PA systolic pressures or PVR > 2/3 systemic equivalent.^6^ Pulmonary vasodilators provide the opportunity to improve haemodynamic balance by decreasing PVR and PAPs to allow for safer surgical repair, termed the ‘treat and repair’ strategy, though the long-term benefits are still not well understood.^7^ In addition, a further complicating factor for surgical decision-making in these patients is the presence of LMCS.

LMCS is the sequelae of long-standing PH with severely dilated pulmonary arterial trunks.^8^ PH has been associated with anginal complaints traditionally attributed to right ventricular ischaemia; however, LMCS is an increasingly recognized contributing factor. In a single-centre study of patients with confirmed PH and PA diameters > 30 mm, LMCA compression of >50% was identified by coronary angiography in 8.2% of the cohort. Another longitudinal prospective analysis of PH patients found LMCA compression in 6% of the entire cohort and 40% of patients who had complaints of angina or anginal-like symptoms.

While coronary artery bypass surgery is the preferred treatment of unprotected LMCA stenosis,^9^ there is increased operative risk in patients with severe PAH–CHD.^10,11^ Patients with CHD often have robust systemic to pulmonary collateral vessels increasing bleed risk of intrathoracic surgery. Moreover, concomitant repair of the underlying CHD at the time of coronary artery bypass graft (CABG) is preferred but dependent on optimization of pulmonary vasodilator therapy through a ‘treat and repair’ strategy. This strategy has limited but evolving data in patients with PAH–CHD, but studies suggest that time to adequate improvement in haemodynamics for consideration of congenital defect correction may be on the order of 1–2 years.^12^ PCI has been established as a reasonable therapeutic approach for the management of LMCS.^13^ A longitudinal evaluation of 53 patients showed no significant complications of the procedure in the periprocedural period, no evidence of stent compression at a 3-month follow-up, and no survival difference between the cohort and a control group at a 5-year follow-up.^14^ In our experience with these two cases, LMCA stenting can serve as a treatment bridge while patients are optimized for corrective surgical treatment of their unpalliated complex CHD.

From a technical standpoint, the use of intravascular imaging to optimize LMCA PCI has evolved over time. Specifically for LMCA PCI, IVUS has been thought to provide better visualization for ostial disease through direct lumen visualization, which overcomes contrast streaming artefact and impact of lesion eccentricity.^15,16^ OCT in general tends to provide better spatial resolution and lesion delineation in the case of coronary artery disease when compared to IVUS but sacrifices on tissue penetration.^17^ The major technical limitation of OCT for LMCA evaluation involves the need for a blood-free field, which requires precise catheter position and ostial selection. A recent prospective, multicentre non-randomized trial looked at the use of OCT-guided PCI for mid- to distal LMCA stenosis and found 86% rate of procedural success and a 98.6% 1-year survival free of major adverse clinical event.^18^ In our experience treating extrinsic left main compression, OCT showed better near-field resolution and was able to better delineate LMCA morphology in the setting of pulsative extrinsic compression.

Supplementary Material