Tunneled left anterior descending artery in a child with ... · signs of heart failure were observed. A 12-lead resting electrocardiogram showed diffuse signs of left ventricular

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Tunneled left anterior descending artery in a child with hypertrophic cardiomyopathyIacopo Olivotto*, Franco Cecchi, Roberta Bini, Silvia Favilli, Bruno Murzi, Ismail El-Hamamsy and Magdi H Yacoub

THE CASEA 10-year-old boy presented with a 4-year history of severe angina on exertion, which had worsened substantially in the last 2 years. On physical examination, the patient was in good general condition, and his body size was normal for his age (height 133 cm; weight 35 kg). Cardiac auscultation was unremarkable, and no signs of heart failure were observed. A 12-lead resting electrocardiogram showed diffuse signs of left ventricular (LV) hypertrophy and LV strain, and a deep Q wave in lead III (Figure 1A). Two-dimensional echocardiography showed mild asymmetric LV hypertrophy localized to the interventricular septum, with a maximum thickness of 15 mm at the midseptal level. The basal septum was irregularly hyperechogenic, which indicated that areas of intramyocardial fibrosis existed (Figure 2). LV systolic function was preserved with a pseudonormal transmitral pulsed wave Doppler pattern.1 In resting con-ditions, no anterior systolic movement of the mitral valve or obstruction of the LV outflow tract (LVOT) was observed. The patient’s family history was unremarkable, and a com-prehensive panel of diagnostic tests excluded a metabolic or mitochondrial cause of the cardio-myopathy. The patient was diagnosed as having nonobstructive hypertrophic cardiomyopathy (HCM). He was started on bisoprolol therapy, and titrated to the maximum tolerated dose of 2.5 mg daily. A maximal, symptom-limited, treadmill exercise test that used a modi-fied Bruce protocol was performed while the patient received treatment, but was terminated early owing to marked downsloping of the ST–T segment on all precordial leads, associ-ated with mild chest discomfort (Figure 1B). A second exercise test yielded very similar results, despite the addition of amlodipine 5.0 mg daily. A 24 h Holter electrocardiogram did not show ventricular or supraventricular arrhyth-mias; however, marked ST–T downsloping was repeatedly evident during moderate physical activity (brisk walking).

SuMMarYBackground A 10-year-old boy presented with a history of severe angina on exertion. A two-dimensional echocardiogram showed mild asymmetric left ventricular (LV) hypertrophy localized to the interventricular septum, consistent with nonobstructive hypertrophic cardiomyopathy. A maximal treadmill exercise test was terminated early owing to marked downsloping of the ST–T segment on all precordial leads, associated with mild chest discomfort. Cardiac MRI and coronary angiography showed that the left anterior descending (LAD) artery was ‘tunneled’ from its origin to the junction of the middle and lower segments, causing systolic obliteration. PET showed diffusely blunted myocardial blood flow after dipyridamole infusion. A beating-heart technique was used to perform surgical mobilization of the superficial and lateral surfaces of the LAD artery. The patient was asymptomatic at 6 months after surgery. A repeat exercise test showed considerable improvement in exercise tolerance, which was associated with a marked decrease in ST–T changes on exertion.

Investigations Physical examination, laboratory tests, 12-lead electrocardiography, two-dimensional echocardiography, exercise testing, cardiac MRI, coronary angiography, PET, Holter electrocardiographic monitoring.

Diagnosis Angina caused by extensive myocardial tunneling of the LAD artery in nonobstructive hypertrophic cardiomyopathy.

Management Bisoprolol therapy and surgical mobilization of the tunneled LAD artery.

Keywords angina, hypertrophic cardiomyopathy, myocardial bridging, myocardial ischemia, myocardial tunneling

I Olivotto is a Staff Physician and F Cecchi is Head of the Referral Center for Cardiomyopathies in the Cardiology Department of Careggi University Hospital, Florence, Italy. R Bini is Chief and Silvia Favilli is a Staff Physician at the Pediatric Cardiology unit, Meyer Pediatric Hospital, Florence, Italy. B Murzi is Chief of the Pediatric Cardiac Surgery unit at the Ospedale Pediatrico Apuano G. Pasquinucci in Massa, Italy. I El-Hamamsy is a Research Fellow in Cardiac Surgery at the Harefield Heart Science Center, London, UK and MH Yacoub is Professor of Cardiac Surgery at Imperial College London, Director of Research at the Harefield Heart Science Centre, Harefield, UK, and Professor of Surgery at the University of Florence, Italy.

Correspondence*Centro di Riferimento per le Cardiomiopatie, Azienda Ospedaliera Universitaria Careggi, Viale Pieraccini 17, 50132 Florence, Italy [email protected]

Received 22 April 200��22 April 200�� Accepted �� eptem�er 200�� eptem�er 200�� Published online XXX 200��

www.nature.com/clinicalpracticedoi:10.103��/ncpcardio1�201�20

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Cardiac MRI demonstrated that the proximal two-thirds of the left anterior descending (LAD) artery had an intramural course, and confirmed the presence of mild, LV septal hypertrophy, with normal LV cavity dimensions and systolic func-tion (Figure 3). Coronary angiography showed extensive obliteration of the LAD artery during systole. Notably, arterial lumen reduction per-sisted during the initial two-thirds of diastole

(Figure 4). Quantitative assessment of LV myo-cardial blood flow by PET after dipyridamole infusion showed an average value of 1.63 ml/min per gram of myocardium, with a blunted vaso-dilator response at the anteroseptal level, in the region of distribution of the LAD artery (Figure 5).2

A surgical approach to management was favored because of persistent symptoms and documented regional ischemia, despite optimum medical therapy. An off-pump beating-heart technique was used for surgical unroofing and mobilization of the LAD artery (Figure 6). On inspection, the anterior LV wall appeared fibrosed. Only the distal third of the LAD artery was observed to have an extramural course and the remaining segments of the artery were deeply embedded in the ventricular septum—12 mm proximally and 5 mm distally below the epicardium. Potts scissors were used to incise the myocardium overlying the vessel. Mobilization of the superficial and lateral surfaces of the LAD artery followed, starting from the superficial segment to the bifurcation of the left main coro-nary artery. Interestingly, a tough, transverse, fibrous band (4 mm in width) covered the LAD artery just distal to the left main coronary artery. This fibrous band was also excised. At the end of surgery, the whole course of the LAD artery had been sufficiently mobilized (Figure 6). No perioperative complications occurred, and the patient made an event-free recovery.

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Figure 1 Results of 12-lead electrocardiography (A) Preoperative resting electrocardiogram showing a deep Q wave on lead III. (B) Electro-cardiogram recorded at peak exercise (1.52 min; �.7 meta�olic equivalents) during preoperative treadmill exercise testing, showing marked and diffuse �T–T segment modifications induced �y exertion. (C) Electrocardiogram recorded at peak exercise (3.5�� min; 7.1 meta�olic equivalents) 6 months after surgery, showing improved exercise capacity and reduction in �T–T segment changes on exertion.


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Figure 2 Preoperative two-dimensional echocardiography (parasternal short-axis view). Maximum left ventricular wall thickness was 15 mm at the midventricular level. (A) Diastole. Mild hypertrophy localized at the anterior septum can �e seen (arrow). (B) �ystole. [ED: Cannot remove the lettering panels on origi-

nal image, too large to edit invisibly]

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At follow-up, 6 months after surgery, the patient was free from angina, although he still complained of fatigue, which was partly a result of muscular deconditioning. A 24 h Holter elec-trocardiogram did not show significant changes of the ST–T segment during daily activities. A repeat exercise test showed substantial improve-ment in exercise tolerance, and marked reduc-tion in ST–T segment changes during exertion (Figure 1C).

DISCUSSION OF DIAGNOSISSymptoms and signs of myocardial ischemia are often evident in patients with HCM, even if the coronary arteries are angiographically normal.3–5 Myocardial ischemia is a major determinant of outcome, and has a complex and multifactorial origin in patients with HCM, which reflects the interplay of structural small-vessel abnor-malities, reduced arteriolar density, myocardial disarray, and elevated LV end diastolic pres-sures.5 In children or adolescents with HCM, however, angina on exertion is often associated with an intramural course of the LAD artery, a condition also referred to as myocardial ‘bridg-ing’.6–13 Systolic compression of an epicardial coronary branch as a result of bridging is seen on angiography in about 15% of patients with HCM,12 compared with a 1–3% prevalence in the general population.13 In the majority of cases of myocardial bridging, the middle segment of the LAD artery is affected.10–13 Although most cases of myocardial bridging in adults are clinically silent and have little bearing

on overall outcome,12 a distinct association seems to exist between myocardial bridging and severe symptoms, ventricular arrhythmias, and sudden death in children with HCM.7 Importantly, the severity of systolic compression is not directly correlated with the degree of hypertrophy or the presence of LVOT obstruction.

Traditional angiography remains the gold standard diagnostic modality for patients with HCM in whom myocardial bridging is suspected as the cause of angina, dyspnea on exertion, or syncope.13 Angiography allows the physician to visualize the location, depth, and length of the bridge, and provides an assessment of the


Figure 3 Cardiac MRI of the left anterior descending artery at end-diastole showing the extended intramural course of the proximal and middle segments of the artery. Arrows indicate the overlying myocardium.


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Figure 4 Coronary angiography (A) �equential stop-frames from the patient’s coronary angiogram showing extensive o�literation of the proximal and mid-left anterior descending artery �y the myocardial tunnel. (B) A plot of the percentage of maximal left anterior descending artery lumen diameter over the whole cardiac cycle showing persistence of lumen reduction over the initial two-thirds of diastole. A��reviations: D, diastolic frames; ED, end-diastole; E�, end-systole; �, systolic frames. [ED/AU: abbreviations aren't used in the figure, should they be? If so, please indicate where]

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severity of compression throughout the cardiac cycle (Figure 4). CT angiography is a useful and reliable alternative to traditional angio-graphy that avoids the risks of invasive coronary imaging. High radiation exposure is, however, an important concern when CT angiography is performed in children.13 Because of techni-cal limitations, the accuracy of cardiac MRI is considerably inferior to traditional angiography or CT angiography for the assessment of coro-nary circulation. However, cardiac MRI serves as a good adjunct to other imaging techniques, and can be used to characterize the depth and extension of the muscle tunnel precisely, to obtain a very detailed three-dimensional image of the heart, and to identify areas of fibrosis. In selected patients, intravascular ultrasonography can be useful in assessing the functional severity of the bridge or tunnel after inotropic stimula-tion,8,10,13 but this technique is not necessary in severe cases, such as the one presented here. Finally, assessment of myocardial flow by PET can help to confirm the functional consequences of coronary compression on regional perfu-

sion during near-maximal vasodilation. In this patient, PET confirmed the causal association between arterial tunneling and the child’s symp-toms (Figure 5).

From a pathophysiological standpoint, myo-cardial bridging results in mechanical com-pression of the artery from both the epicardial and lateral aspects.8 In addition, repeated sys-n addition, repeated sys-tolic compression of the coronary vessel leads to increased wall shear stress and impairment in endothelium-dependent vasorelaxation.9 These functional alterations are thought to add to the severity of structural lumen compres-sion, and contribute to clinical manifestations of myocardial bridging. Indeed, angiographic and intravascular ultrasonographic studies have shown that vessel compression during systole is followed by a delay in luminal diameter increase during diastole, which affects the predominant phase of coronary perfusion, as seen in this patient.10 In its most severe form, such as in the individual described here, extensive myocardial bridging is more appropriately referred to as a ‘tunneled’ LAD artery. The extension and depth of the intramyocardial course of the artery are important determinants of ischemia and associ-ated symptoms, and help distinguish forms that are clinically relevant from those that are not.6,10,11

An assessment of the links between myo-cardial tunneling, ischemia and symptoms can be a challenge in patients with HCM. Myocardial ischemia is often clinically silent, whereas chest pain is a frequent complaint but is often atypi-cal and not a reliable marker of ischemia.3–5 However, in this patient, the clinical presenta-tion included typical exertion-related angina and striking electrocardiographic changes during exercise, which left little doubt about the presence of ischemia. The severity of coronary compression during most of the cardiac cycle, the regional impairment of blood flow seen on PET and the absence of LVOT obstruction or severe hypertrophy all strongly supported a direct causal link between the tunneled LAD artery and the patient’s symptoms.

TREATMENT AND MANAGEMENTManagement strategies for patients with HCM and symptomatic myocardial tunneling have not been adequately investigated, nor has the optimal therapy been defined. Asymptomatic patients, in whom myocardial bridging is an unexpected finding, should undergo exercise testing and a


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Figure 5 Nitrogen-13 ammonia PET polar map that illustrates the regional values of myocardial �lood flow after dipyridamole injection. The values 1.115�� and �.��0��6 indicate the minimum and maximum value of flow, expressed in ml/g of tissue per minute, that was measured in the left ventricle after dipyridamole injection. The lowest values are coded in dark colors from red to �lack, and the highest values in light colors from yellow to white. The pattern shown in the map is consistent with �lunted response to dipyridamole in the anteroseptal wall, the region of distri�ution of the anterior descending artery.



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series of ambulatory Holter electrocardiograms to assess the presence of inducible ischemia and ventricular arrhythmias. In the absence of either finding, adult patients can be managed conservatively.12 In the presence of symptoms or exercise-induced ischemia, an initial approach with β-blockers can be effective for controlling angina, although the long-term efficacy of this strategy has not been assessed.10,13 β-blockers control tachycardia, thereby increasing diastolic perfusion time, and reduce the contractility of the myocardial tunnel. Conversely, nitrates can worsen symptoms and the degree of systolic coro-nary compression, and should be avoided.10

When symptoms attributable to myocardial tunneling persist despite optimum medical therapy, surgery is generally agreed to be the best option.10,13,14 Ultimately, the decision to operate should be on the basis of surgical risk, the experi-ence of the surgical team, and whether LAD artery tunneling exists in association with LVOT obstruction. In a limited number of reports, including small patient series and isolated case studies, relief of symptoms and ischemia after surgery have been consistently described, although the ultimate effects on long-term outcome remain to be established.13 Downar et al.15 reported that, in five children from the Toronto HCM cohort, myocardial bridges that caused compression of the LAD artery (associ-ated with severe clinical manifestations and evidence of myocardial ischemia) were success-fully treated with supra-arterial myotomy. The authors reported substantial improvement or resolution of cardiac symptoms, without major perioperative complications.15 Notably, these operations were performed on cardiopulmonary bypass. However, we believe that the optimum surgical approach should involve a beating-heart technique, which significantly reduces opera-tive times and risks, and mobilizes the super-ficial and—importantly—the lateral aspects of the artery.8 Such an approach was successfully adopted in the current patient.

Notably, coronary stenting has been attempted as an alternative to surgery in patients with myo-cardial bridging who do not have HCM.10,16 However, this approach is associated with a high rate of major periprocedural complications or short-term restenosis,13 and should be avoided, particularly in children.

This young patient experienced rapid and marked postoperative improvement in sympto-matic status, which was associated with an

objective reduction in electrocardiographic abnormalities during exercise. Persistence of mild symptoms related to exercise could be a result of diffuse microvascular dysfunction causing residual hypoperfusion of the myo-cardium,2 as well as to muscular deconditioning. In addition, endothelial dysfunction of the LAD artery might have persisted, caused by extended vessel exposure to mechanical stress during systole.9 Further investigation is needed to test this hypothesis.

CONCLUSIONSTunneling of the LAD artery can be the cause of severely limiting symptoms in children with HCM, and should always be suspected in the presence of angina or other manifestations of myocardial ischemia. Surgical correction can be performed successfully with the use of a beating-heart approach. We hope that the detailed dis-cussions of the pathophysiology of the condition, and the surgical technique, presented in this Case Study will help optimize the management of children with HCM who are affected by this potentially serious condition.


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Figure 6 �urgical correction of myocardial tunneling. (A) On inspection, only the distal third of the left anterior descending artery was o�served to have an extramural course. The remaining course of the artery was intramural (arrowheads). (B) �urgical mo�ilization of the superficial and lateral aspects of the artery, using a �eating-heart technique. The white arrow indicates a fi�rous �and overlying the artery. (C) Mo�ilization of the proximal left anterior descending artery. (d) The completed operation.

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AcknowledgementsWritten consent for pu�lication was o�tained from the patient’s mother.

Competing interestsThe authors declared no competing interests.

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