Interventional Treatment for Children With Severe Coronary Artery Stenosis With Calcification After Long-term Kawasaki Disease
Background About 4% of children with Kawasaki disease (KD) eventually develop ischemic heart disease, which is often associated with calcified stenosis. We assessed the utility of the percutaneous transluminal coronary rotational ablation (PTCRA) in children with coronary artery stenosis after KD.
Methods and Results Four children (three boys and one girl; age, 12 to 13 years) with coronary artery stenosis underwent percutaneous transluminal coronary angioplasty (PTCA) and PTCRA 11.8±0.9 years after the onset of KD. Morphology of the coronary artery wall was evaluated by intravascular ultrasound imaging. In one patient, the targeted lesion for intervention was in the left anterior descending artery (90% stenosis); in the other three patients, it was in the middle of the right coronary artery (75% to 90% stenosis). PTCA failed in three patients because of severe stenosis with calcification. However, PTCRA proved effective, with stenosis rates reduced from 90% to 25%. Follow-up coronary angiography performed 4 months after the procedure demonstrated no restenosis, but mild aneurysms occurred in two patients.
Conclusions This study suggests that PTCRA is useful for revascularizing coronary arteries with severe stenosis and calcification as long-term sequelae of KD. Intravascular ultrasound imaging is useful in assessing the coronary artery wall pathology and in selecting the best treatment intervention.
Between 10% and 20% of children with acute KD have coronary aneurysms, and about 4% of all KD patients develop ischemic heart disease during long-term follow-up.1–3 Coronary stenosis is an important issue because it may cause myocardial infarction.3,4 Interventions such as PTCA, atherectomy, or stent implantation are now common treatments for adults with coronary artery disease.5,6 However the use of these treatments is limited in KD.7 In particular, PTCA is not as effective in KD patients as in others because the stenotic lesions in long-term KD are stiff and often are associated with calcification. The efficacy of PTCRA for coronary lesions with calcification was recently reported in adults.8,9 We assessed the utility and the indications for PTCRA or PTCA in children with coronary stenosis after KD.
Four children (three boys and one girl) with coronary stenosis after KD underwent PTCA or PTCRA. Their minimum age was 12 years (mean, 12.7±0.6 years), and they had been followed for 11.8±0.9 years after the onset of KD. None had a history of myocardial infarction. The three boys had giant coronary aneurysms at the middle of the RCA, and the girl had coronary aneurysms in the LAD and in the middle RCA at the acute stage of KD. All patients were administered aspirin 5mg/kg daily from the acute stage of KD. Stenosis of the coronary arteries was detected by follow-up angiography 6 to 12 years after the onset of KD and had progressed to >75% stenosis. Clinical characteristics of the patients are summarized in the Table⇓.
The study protocol was approved by the Kurume University School of Medicine Ethics Committee. Informed consent was obtained from the parents of all patients.
A 9F sheath was inserted percutaneously into the femoral artery. Through it, a 5F or 6F Judkins-Kato catheter for pediatric coronary angiography (Cook Comp) was advanced to the ostium of the RCA or LCA by use of the Judkins technique. We measured the systemic arterial pressure through the sheath and checked the heart rate by ECG monitoring. Cineangiography of the LCA and RCA was performed by manual injection of Iohexol through an angiographic catheter under ECG monitoring. The right anterior oblique 30° projection, the posterior anterior projection, or the left anterior oblique 60° projection was used. After the coronary artery lesions were ascertained, IVUS and PTCRA or PTCA were performed. Heparin administration was carried out, and the activated clotting time was maintained at >300 seconds.
Interventional Procedure (PTCA or PTCRA)
Oral premedication included aspirin and calcium channel antagonists. A 6F pacing catheter was inserted into the right ventricle, and intracoronary injection of isosorbide dinitrate (1 mg) was performed before PTCA or PTCRA.
Initially, PTCA was tried in all patients. However, the catheter failed to advance into the target lesions because of severe stenosis in three patients. The PTCA balloon catheter (ASUKA) was advanced over a 0.014-in angioplasty guide wire and positioned at the target coronary lesion. Two or three 30-second balloon inflations were performed at pressures ranging from 5 to 10 atm. The balloon was changed, and the diameter was sequentially increased from 2.5 to 4.0 mm.
Rotational ablation was performed in the three patients in whom PTCA was not successful. Then a 9F high-flow coronary guiding catheter was used to cannulate the target vessel, and the Rotablator was advanced to the coronary lesion while spinning at 160 000 to 180 000 rpm over a 0.009-in (0.023-cm) Rotablator guide wire. The Rotablator (Heart Technology Inc) consists of a football-shaped, stainless steel burr impregnated with diamond microchips (diameter, 30 to 50 μm) and is powered by a compressed air–driven turbine. The burr was changed, and the diameter was sequentially increased 1.25 to 2.25 mm.
Patients were discharged 3 days after the interventional procedure on a maintenance dose of aspirin (5 mg · kg−1 · d−1). A follow-up coronary angiography and IVUS were performed 4 months later.
Intravascular Ultrasound Imaging
Insertion of the imaging catheter was difficult before the interventional procedures (PTCA and PTCRA) in three patients; in two of these patients, the imaging catheter placement was successful after the intervention. The sheath was placed in the femoral artery, and then a 7F or 8F right or left Judkins large-lumen guiding catheter with a 0.14-in angioplasty guide wire was advanced into the coronary ostium. After this guide wire was withdrawn, an ultrasound imaging catheter with a 30-MHz transducer (CVIS Inc) at the tip was advanced over a another finer guide wire (0.014-in) through the guiding catheter to record the coronary artery lesion. The size of the ultrasound imaging catheter was 4.3F. The intracoronary ultrasound image was displayed on a fluoroscope. The location of the tip of the IVUS catheter was determined by angiography. The IVUS was recorded on videotape. The images of the important coronary lesions also were recorded on Polaroid photographic paper.
Analysis of Wall Morphology and Lumen Size
The coronary artery wall morphology was evaluated for the echogenicity of the wall structures, intimal thickening, presence of calcification, and lumen size. We chose the better interventional method for each patient. PTCA was performed in patients who had coronary artery stenosis with hard plaque or calcification of <50% around the surface of the lumen, whereas PTCRA was performed in those with stenosis and calcification of >50% or in whom severe stenosis prevented insertion of the PTCA catheter. The smallest axis of the site in the coronary artery was identified by visual inspection, and the diameter was measured by placing an electronic cursor at the acoustic interface between the lumen and the intimal leading edge at opposite sides of the coronary artery on the IVUS image.
All patients underwent heparinization during the PTCA or PTCRA procedure and received aspirin postoperatively. Preoperative and postoperative analyses included creatine kinase measurement every 8 hours for 24 hours and daily ECGs during hospitalization for 3 days.
Results of Coronary Intervention
Case 1: 13-Year-Old Girl
The RCA demonstrated total occlusion with a bridging collateral artery. The LAD had 90% (Fig 1A⇓). We could not perform PTCA because it was difficult to insert the PTCA catheter through the severely narrowed segment. However, PTCRA was performed by use of the 2.0-mm rotational ablation catheter burr in the LAD. The stenosis was improved from 90% to only 25% by the procedure (Fig 1B⇓). On IVUS, performed after the ablation, calcification and intimal thickening were demonstrated on the surface of the lumen side of the intima, and an acoustic shadow was detected in the left wall of the vessel. The wall had no dissection or rupture at the site of stenosis (Fig 1C⇓).
Case 2: 13-Year-Old Boy
On angiography, the LCA was intact without aneurysms, stenosis, or irregular lesions. The RCA demonstrated 75% localized stenosis at the site of the proximal segment (Fig 2A⇓). At this site, intimal thickening and calcification were observed on IVUS before PTCA (Fig 2D⇓). The calcification was located on the surface of lumen side of the intima. The other side of the intima demonstrated only low echogenicity, indicating that it was composed of soft tissue. After PTCA was performed (3 mm at 5 atm and 3.5 mm at 5 atm for 30 seconds), the degree of right coronary stenosis improved from 75% to 25% (Fig 2B⇓). The IVUS demonstrated a dilated lumen without dissection of the intima at the site of the procedure just after the PTCA procedure (Fig 2E⇓).
Case 3: 13-Year-Old Boy
The LCA was intact on angiography, without aneurysms, stenosis, or irregular lesions. The RCA demonstrated 90% localized stenosis at the site of the proximal segment (Fig 3A⇓). Calcification was detected at the site by fluoroscopy. Because it was difficult to insert the catheter through the severely narrowed segment, PTCA could not be performed. After coronary angiography, PTCRA was performed with maximum diameter of the rotational ablation catheter burr (2.25 mm). The stenosis decreased from 90% to less than 25% after PTCRA (Fig 3B⇓). When IVUS was performed after the ablation, calcification was demonstrated on all surfaces of the lumen side of the intima, with an acoustic shadow at the target site. The wall had no dissection or rupture at the site (Fig 3D⇓).
Case 4: 12-Year-Old Boy
The LCA showed mild dilatation without stenosis or irregular lesions in the main tract on angiography. The RCA demonstrated 90% localized stenosis at the site of the proximal segment (Fig 4A⇓). Calcification was detected at the site by fluoroscopy. We could not perform PTCA because it was difficult to insert the balloon catheter through the severely narrowed segment of the site. After coronary angiography, PTCRA was performed. Ablation of the site was achieved by the maximum diameter of the rotational ablation catheter burr (2.25 mm). The stenosis decreased from 90% to 50% after PTCRA (Fig 4B⇓). On IVUS, performed after the procedure, calcification was located on the surface of the lumen side of the intima, and the other side of the intima seemed to be soft tissue (Fig 4E⇓). After PTCRA, PTCA was performed at the site of the procedure (3 mm at 5 to 10 atm and 3.5 mm at 5 to 10 atm For 60 seconds), which further decreased the stenosis from 50% to <25% (Fig 4C⇓). Localized dissection at the intima with calcification was demonstrated by IVUS after PTCA (Fig 4F⇓).
Follow-up coronary angiography and IVUS were performed 4 months after the PTCA or PTCRA treatment. No patient developed restenosis at the coronary artery where the procedure had been done (Figs 2C⇑, 3C⇑, and 4D⇑). New aneurysms appeared at the site of PTCA in cases 2 (Fig 2C⇑) and 4 (Fig 4D⇑). Progression of intimal thickening or presence of thrombus was not demon-strated in any patient by IVUS. No patient had ischemic findings in a follow-up exercise stress test, echocardiography, or ECG at rest. These patients were released from restriction on exercise. The patients remained on aspirin (5 mg · kg−1 · d−1). They were followed up 12 to 18 months after the procedure. They have had no symptoms or events that suggest the presence of ischemic heart disease.
No ischemic events such as acute myocardial infarction, angina pectoris, or coronary artery rupture occurred during PTCA or PTCRA treatment. However, the RCA lesion progressed to a new aneurysm in cases 2 and 4, as demonstrated by the follow-up coronary angiography 4 months after PTCA. Localized intimal dissection was demonstrated by IVUS just after the PTCA in case 4.
Utility and Outcome
Catheter intervention treatment is now widely accepted as a nonsurgical revascularization option for adult patients with coronary artery disease. However, the experiences in KD have been limited.7,10,11 In contrast to the success of PTCA for treatment of atheromatous coronary artery disease in the adult, it was reported10,11 that PTCA is not as effective in the dilatation of the severely calcified stenotic lesions in patients with KD via balloon angioplasty. In this study, we introduced the new device of PTCRA, which was effective in ablating stenotic vessel lesions with hard calcification in the children with coronary artery stenosis after KD. Although PTCA was effective in only one of our four patients, the other three required PTCRA to ablate the hardened stenotic coronary lesions.
The mechanism of coronary artery stenosis in KD is uncertain. One possibility is acute occlusion by massive thrombus formation in the coronary aneurysms, which occur mostly in acute or subacute stages of illness. Another mechanism of coronary artery stenosis after KD may be the progression of marked thickening of the intima often associated with calcification, which is similar to an arteriosclerotic lesion.12,13 In our only patient in whom a PTCA catheter could be inserted through a stenotic coronary lesion, the wall structure at the site of coronary stenosis had a localized area of high echogenicity on the inner surface of the lumen and in other areas had intimal thickening without calcification, as assessed by IVUS. Ino et al7 reported that PTCA should be attempted within 6 to 8 years after KD, which means that the stenotic lesions may develop arteriosclerotic changes over the long term. We conclude that PTCA may successfully dilate stenotic coronary arteries that have relatively soft intima with only localized mild calcification. However, PTCRA may be the most useful method for intervention in cases of long-term coronary stenosis after KD. Interventional devices (PTCRA or PTCA) must be selected based on assessment of wall morphology and tissue characteristics by IVUS.
Myocardial infarction, arrhythmias, and death during PTCRA have been reported in the coronary artery disease.8,9 Death in a child after KD was attributed to acute LAD occlusion from balloon rupture during a PTCA procedure.10 No such serious cardiac events occurred in our study. Creatine kinase was not elevated in our four patients, and their ECGs demonstrated no abnormal Q waves or ST-T changes.
The RCA lesion progressed to a new aneurysm in case 2 and in case 4 four months after the interventional procedures. These patients underwent PTCA (in case 4, PTCA was performed after PTCRA) with a relatively high pressure in the balloon. The new aneurysm may have occurred because of PTCA. It is necessary to study how much pressure in the balloon is adequate for PTCA after KD. We speculated that the Rotablator procedure did not result in aneurysms because the procedure can shatter the calcification at the coronary stenotic lesion without high tension to the coronary vessel wall.
Restenosis and Follow-up
Restenosis occurred in 17% to 52% of adult patients with coronary artery disease after PTCA or PTCRA.14–16 Teirstein et al17 reported that restenosis occurred less frequently in patients with localized stenotic lesions after PTCRA. Nobuyoshi et al15 reported that restenosis is most prevalent between 1 and 3 months and rarely occurs beyond 3 months after PTCA in adults. We performed follow-up angiography 4 months after PTCA or PTCRA in children who had KD. None developed restenosis at the site of the coronary lesions on follow-up coronary angiography or IVUS. The outcome in KD patients with localized, short-term stenosis of the coronary artery after PTCA or PTCRA may be favorable, but further follow-up is necessary to evaluate the possibility of coronary aneurysm.
Indications and Limitations
The method of coronary intervention for children after KD is not established at the present time. American College of Cardiology/American Heart Association guidelines18 have been used for PTCA in adult patients with symptomatic ischemic status without major complications. In this study, we chose patients with >75% localized stenosis in the coronary artery who had no history of myocardial infarction and no ischemic symptoms. The coronary stenotic lesions of KD had rich calcification and intimal thickening with coronary aneurysm.12 The site of coronary stenosis in KD was hard and stiff, indicating that the lesions had developed over a long time. As a result, the procedure of PTCA or PTCRA became increasingly difficult because the cath-eter could not be inserted into the severe coronary stenosis. PTCA or PTCRA should be performed to prevent myocardial infarction or sudden death in patients with 75% coronary stenosis after KD and unrelated symptomatic ischemic status. Stent implantation is another important strategy for adults with coronary artery disease. However it may be difficult to insert a catheter or stent into the severe stenotic and stiff lesions with calcification after KD. For PTCA or stent implantation in KD patients, we should select patients with moderate stenotic lesions, probably within 6 to 8 years from the onset of KD.7 One of the great limitations of coronary intervention is that the PTCA or PTCRA catheter is too big for infants and young children. In the future, we need a smaller interventional catheter that may contribute greatly to the increased indications for and use of these methods in young children.
This study suggests that PTCRA is a safe, effective treatment for revascularization of severe stenosis with calcification as long-term coronary artery sequelae after KD. The procedure can postpone aortocoronary bypass surgery. Furthermore, IVUS is useful in the assessment of wall morphology and tissue characterization of the pathological coronary artery as well as in the selection of the best device for interventional treatment. We hope that our study leads to progressive interventional trials using this procedure for the treatment of children with coronary stenosis.
Selected Abbreviations and Acronyms
|IVUS||=||intravascular ultrasound imaging|
|LAD||=||left anterior descending coronary artery|
|LCA||=||left coronary artery|
|RCA||=||right coronary artery|
|PTCA||=||percutaneous transluminal coronary angioplasty|
|PTCRA||=||percutaneous transluminal coronary rotational ablation|
- Received April 29, 1997.
- Revision received August 18, 1997.
- Accepted August 28, 1997.
- Copyright © 1997 by American Heart Association
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