CASE REPORT

Unusual Cause of Myocardial Ischemia in an Infantchd_673 1..4

Smita Mehta, MD, Richard J. Sterba, MD, Gerard J. Boyle, MD, and Peter F. Aziz, MD

Division of Pediatric Cardiology, Center for Pediatric and Congenital Heart Disease, Cleveland Clinic Foundation,Cleveland, Ohio, USA

A B S T R A C T

Abnormal coronary artery anatomy should be ruled out in any patient with myocardial dysfunction and an abnormalelectrocardiogram. The reported etiologies of infantile myocardial ischemia are abnormalities of coronary arteries,perinatal asphyxia, umbilical catheterization, and myocarditis. Generalized arterial calcification of infancy, althoughrare, should be considered in the differential diagnosis of infantile myocardial ischemia if coronary artery origin isfound to be normal on echocardiography.

Key Words. Myocardial Ischemia; Infant; GACI

Case Report

A2-month-old female infant presented to anoutside hospital with a 2-week history of tac-

hypnea, irritability, and poor feeding. She was paleand poorly perfused with significant metabolic aci-dosis (pH 6.9, HCO3 12 mEq/L). She was intu-bated, started on inotropes, and transferred to theintensive care unit. The electrocardiogram (ECG)showed evidence of a possible lateral wall myocar-dial infarction. The echocardiogram showed astructurally normal heart with coronary arteryorigins arising from the right and left coronarysinuses. There was moderate left ventricular(LV) dysfunction with a shortening fraction of21%. There was a left-to-right shunt through apatent foramen ovale. The admission troponinwas 1.7 ng/mL. The admission diagnosis wasmyocarditis.

As she became hemodynamically stable, ino-tropes and ventilator settings were weaned. Justbefore an extubation attempt, she decompensatedand required full support again. Her troponinincreased from 1.7 ng/mL at admission to25 ng/mL over the next 3 days. She initially toler-ated extubation a few days later, but soon devel-oped tachycardia, had clinical signs of decreasedcardiac output, worsening LV systolic and diastolicdysfunction, lactic acidosis, and was reintubated.

She was transferred from the outside hospital toour pediatric intensive care unit (PICU) withrefractory congestive heart failure for transplantevaluation. She arrived intubated, mechanicallyventilated, and on inotropes. Her arms and legswere mottled and cool. Her pulses were decreased.She had an S4. Her liver was 5 cm below the rightcostal margin.

She had ECG findings of Q waves in the lateralleads and ST segment changes (Figure 1) consis-tent with myocardial ischemia. Our initialechocardiogram demonstrated the regional wallmotion abnormality noted on her previousechocardiogram at the outside hospital. We feltthat an ECG suggesting a lateral wall myocardialinfarction and an echocardiogram showing asimilar abnormality needed better definition ofcoronary artery anatomy. She was therefore takento the cardiac catheterization laboratory toconfirm the coronary artery origins and assesshemodynamics. The angiograms showed normalorigins of the coronary arteries (Figure 2) withpoor filling of the coronary artery tree (Figure 3).In particular, there was a filling defect at the levelof left anterior descending (LAD) and LCx bifur-cation (Figure 4). Septal perforators off the LADshowed diminished flow as did the diagonalbranches. The acute marginal branch of the rightcoronary artery also displayed compromised flow.

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© 2012 Wiley Periodicals, Inc. Congenit Heart Dis. 2012;••:••–••

Collateral flow was noted. There was no improve-ment in coronary flow after 15 mL nitroglycerineinfusion. She was transferred back to the PICU,where the rheumatology and genetics serviceswere consulted for possible causes, including con-genital causes, of her findings. Generalized arterial

calcification of infancy (GACI) was suggested as apossible cause. The abdominal ultrasound notedmultiple arterial calcifications in the kidneys(Figure 5). Additional studies revealed similarvessel calcifications in the spleen and liver. A ret-rospective review of the abdominal x-ray showedpunctate densities over the gastric bubble (repre-senting splenic calcifications), and subcutaneous

Figure 1. 12-lead ECG at admission.

Figure 2. Aortic root injection showing normal coronaryartery origins.

Figure 3. Selective coronary artery injection showingdiffuse narrowing.

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calcification was suggested at the base of the neckand axillae on the chest x-ray.

GACI was first described in the literature in1948.1 There are additional case reports in 1954,21955,3 and 1957.4 Twenty years later, more reportswere published, starting in 1980.5 Briefly, GACI,referred to sometimes as idiopathic infantile arte-rial calcification, is characterized by hydroxyapa-tite deposition in the internal elastic lamina ofmedium- and large-sized arteries.6 It may beaccompanied by periarticular calcification. The

underlying genetic disorder is a loss-of-functionmutation in the ENPP1 gene.7,8 The patient’sENPP1 test revealed no detectable disease-causing mutation. There are multiple case reportsof successful treatment with parenteral and oralbisphosphonate therapy for varying lengths oftime.6,9,10 Some patients may have a more favorableclinical course.11,12 The patient was started onparenteral bisphosphonate therapy and subse-quently transitioned to an oral bisphosphonate.Mortality in GACI is almost always linked to ven-tricular dysfunction resulting from infarction dueto coronary arterial stenosis induced by myointi-mal proliferation and calcification.7 The patient isnow 7 months old and continues to be followed bythe transplant/heart failure service; her parentshave declined the option of cardiac transplantationand she is not listed at this time.

Abnormal coronary artery anatomy should beruled out in any patient with myocardial dysfunc-tion and an abnormal ECG. The electrocardio-graphic features of Q waves and ST segmentelevation in the lateral leads led to further evalua-tion of the coronary artery anatomy by angio-graphic imaging. Our patient had the ECGfeatures of segmental myocardial ischemia buton echocardiography did not have evidence ofthe most common congenital coronary arteryanomaly, an abnormal origin of the left coronaryartery from the pulmonary artery, which led tothe cardiac catheterization for further evaluation.The reported etiologies of infantile myocardialischemia are abnormalities of coronary arteries,perinatal asphyxia, umbilical catheterization, andmyocarditis. GACI, although rare, should be con-sidered in the differential diagnosis of infantilemyocardial ischemia if coronary artery origin isfound to be normal on echocardiography. Coro-nary artery anatomy should be further visualizedpromptly by angiography to delineate the lesionsresponsible for the infant’s myocardial ischemia.

Author Contributions

Smita Mehta, MD: Drafting case report.

Richard J. Sterba, MD: Critical revision of article.

Gerard J. Boyle, MD: Critical revision of article.

Peter F. Aziz, MD: Concept/Design/Critical revision ofarticle.

Corresponding Author: Smita Mehta, Fellow, MD,Division of Pediatric Cardiology, Center for Pediatricand Congenital Heart Disease, Desk M41, Cleveland

Figure 4. LCA hypoperfusion on angiogram.

Figure 5. Right kidney ultrasound in transverse sectionshowing vascular calcifications.

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GACI in an Infant 3

Clinic Foundation, 9500 Euclid Avenue, Cleveland,OH 44195, USA. Tel: (+216) 636-9042; Fax: (+216)445-5679; E-mail mehtas2@ccf.org

Conflict of interest: None.

Accepted in final form: March 27, 2012.

References

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6 van der Sluis IM, Boot AM, Vernooij M, Meradji M,Kroon AA. Idiopathic infantile arterial calcification:clinical presentation, therapy and long-term follow-up. Eur J Pediatr. 2006;165:590–593.

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9 Ramjan KA, Roscioli T, Rutsch F, Sillence D,Munns CF. Generalized arterial calcification ofinfancy: treatment with bisphosphonates. Nat ClinPract Endocrinol Metab. 2009;5:167–172.

10 Edouard T, Chabot G, Miro J, et al. Efficacy andsafety of 2-year etidronate treatment in a child withgeneralized arterial calcification of infancy. Eur JPediatr. 2011;170:1585–1590.

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