greater HF HRV.18 Another study in patients afteracute myocardial infarction found no relation betweenthe ACE I/D polymorphism and HRV.19 There areseveral important differences between these previousstudies and the present study. First, in both of theprevious studies, the populations were composed ex-clusively of Caucasian participants. Second, 1 studyexamined patients after a major cardiac event, inwhich HRV levels tend to be depressed and duringwhich time other factors, such as renin-angiotensinsystem activation, may be dominant.19 Third, we ex-amined a number of possible variables, including thepresence of disease that could explain and moderatethe relation between ACE I/D and HF HRV. This wasnot done in the previous studies and may help toaccount for the observed discrepancy with the presentresults.

The urban African-American population studied inthe present report is at particularly high cardiovascularrisk.20 The ACE I/D DD genotype may contribute tothe already increased cardiovascular risk in this pop-ulation.

1. Singh JP, Larson MG, O’Donnell CJ, Tsuji H, Evans JC, Levy D. Heritabilityof heart rate variability: the Framingham Heart Study. Circulation 1999;99:2251–2254.2. Sinnreich R, Freidlander Y, Luria MH, Sapoznikov D, Kark JD. Inheritance ofheart rate variability: the Kibbutzim family study. Hum Genet 1999;105:654–661.3. Rigat B, Hubert C, Alhenc-Gelas F, Cambion F, Corvol P, Soubrier F. Aninsertion/deletion polymorphism in the angiotensin I-converting enzyme geneaccounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–1346.4. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, BardJM, Bara L, Ricard S, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature1992;359:641–644.5. Schunkert H, Hense H-W, Holmer SR, Stender M, Perz S, Keil U, Lorell BH,

Reigger GAJ. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994;330:1634–1638.6. Butler R, Morris AD, Burchell B, Struthers AD. DD angiotensin-convertingenzyme gene polymorphism is associated with endothelial dysfunction in normalhumans. Hypertension 1999;33:1164–1168.7. Ueda S, Elliott HL, Morton JJ, Connell JMC. Enhanced pressor response toangiotensin I in normotensive men with deletion genotype (DD) for angiotensin-converting enzyme. Hypertension 1995;25:1266–1269.8. Kohno M, Yokokawa K, Minami M, Kano H, Yasunari K, Hanehira T,Yoshikawa J. Association between angiotensin-converting enzyme gene poly-morphisms and regression of left ventricular hypertrophy in patients treated withangiotensin-converting enzyme inhibitors. Am J Med 1999;106:544–549.9. Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: A Laboratory Man-ual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1989:16–19.10. Evans AE, Poirier O, Kee F, Lecerf L, McCrum E, Falconer T, O’RourkeeDF, Cambien F. Polymorphism of the angiotensin-converting-enzyme gene insubjects who die from coronary heart disease. Quart J Med 1994;87:211–214.11. Task Force of the European Society of Cardiology and North AmericanSociety of Pacing and Electrophysiology. Heart rate variability: standards ofmeasurement, physiological interpretation, and clinical use. Circulation 1996;93:1043–1065.12. Tsuji H, Venditti FJ, Manders ES, Evans JC, Larson MG, Feldman CL, LevyD. Determinants of heart rate variability. J Am Coll Cardiol 1996;28:1539–1546.13. Niemela MJ, Airaksinen KEJ, Huikuri HV. Effect of beta-blockade on heartrate variability in patients with coronary artery disease. J Am Coll Cardiol1994;23:1370–1377.14. Parati G, Frattola A, Di Rienzo M, Castiglioni P, Mancia G. Broadbandspectral analysis of blood pressure and heart rate variability in very elderlysubjects. Hypertension 1997;30:803–808.15. Craft N, Schwartz JB. Effect of age on intrinsic heart rate, heart ratevariability, and AV conduction in healthy humans. Am J Physiol 1995;268:H1441–H1452.16. Freeman R, Saul JP, Roberts MS, Berger RD, Broadbridge C, Cohen RJ.Spectral analysis of heart rate in diabetic neuropathy. Arch Neurol 1991;48:185–190.17. Karason K, Molgaard H, Wikstrand J, S, Jostrom L. Heart rate variability inobesity and the effect of weight loss. Am J Cardiol 1999;83:1242–1247.18. Busjahn A, Voss A, Knoblauch H, Knoblauch M, Jeschke E, Wessel N,Bohlender J, McCarron J, Faulhaber H-D, Schuster H, Dietz R, Luft FC. Angio-tensin-converting enzyme and angiotensin gene polymorphisms and heart ratevariability in twins. Am J Cardiol 1998;81:755–760.19. Steeds RP, Fletcher J, Parry H, Chowdhary S, Channer KS, West J, TownendJN. The angiotensin-converting enzyme gene I/D polymorphism and heart ratevariability following acute myocardial infarction. Clin Auton Res 2002;12:66–71.20. Winkleby MA, Cubbin C, Ahu DK, Krowmer HC. Pathways by which SESand ethnicity influence cardiovascular disease risk factors. Ann NY Acad Sci1999;896:191–209.

Coronary Tracheal Collaterals AfterHeart–Lung Transplant

Satinder Pal Singh, MD, Hrudaya Nath, MD, David McGiffin, MD, andJames Kirklin, MD

Coronary tracheal collaterals are often seen on an-nual surveillance coronary angiograms in patientswith heart–lung transplants and represent a normalpostoperative finding. �2003 by Excerpta Medica,Inc.

(Am J Cardiol 2003;92:1490–1492)

Annual surveillance coronary angiography is stan-dard practice in patients with heart and heart–

lung transplantation (HLT) to detect coronary arterial

disease reflecting graft rejection. Several other abnor-malities, such as congenital anomalies and fistulouscommunications due to endomyocardial biopsy pro-cedures, are also incidentally detected from these an-giograms. Over the years we have noticed abnormalvascular supply from the coronary arteries to the sub-carinal region of the mediastinum in patients whohave undergone HLT, which could be confused withcoronary arteriovenous malformation. These abnor-mal-appearing vessels represent collateral supply tothe transplanted proximal tracheobronchial tree. Thepurpose of this communication was to evaluate thisphenomenon in patients with HLT.

• • •Sixteen patients who underwent HLT during a

13-year period (from 1989 to 2002) were included in

From the Departments of Radiology and Cardiothoracic Surgery, Uni-versity of Alabama at Birmingham, Birmingham, Alabama. Dr. Singh’saddress is: Department of Radiology, University of Alabama at Bir-mingham, 619 South 19th Street, Birmingham, Alabama 35233.Manuscript received May 22, 2003; revised manuscript received andaccepted August 22, 2003.

1490 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 December 15, 2003 doi:10.1016/j.amjcard.2003.08.071

the study. HLT was performed in 15 patients at ourinstitution, and 1 patient was referred to us 3 yearsafter HLT at another institution. The indications forHLT included primary pulmonary hypertension (4),Eisenmenger physiology (9), bronchopulmonary dys-plasia (1), bronchiolitis obliterans (1), and end-stageischemic heart disease with severe pulmonary hyper-tension (1). Serial, annual surveillance coronary an-giograms were recorded in 13 of 16 patients and 1

patient was seen for the first time 3 years after surgery.Two patients died before the first anniversary of trans-plantation. Thus, coronary angiograms in 14 patientswere reviewed. Coronary angiograms were evaluatedfor coronary artery occlusive disease, other incidentalfindings, and observation of coronary tracheal collat-erals (source, number, change in size). The abnormalvessel was subjectively graded from 0 to 3 to detectsubtle abnormalities and to assess its progression: 0 �normal; 1 � collateral vessels present, same size asnormal atrial branches (Figure 1); 2 � presence ofcollateral vessels that are larger than the normal atrialbranch (Figure 2); and 3 � extensive collateral vessels

FIGURE 1. Lateral view of a right coronary angiogram of a 36-year-old man who had HLT for Eisenmenger physiology. The en-larged sinoatrial nodal artery (arrows) is seen coursing upwardtoward the carina. This represents a grade 1 collateral vessel.

FIGURE 2. Left coronary arteriography in the right anterioroblique projection in a patient who underwent HLT for primarypulmonary hypertension. A large collateral vessel from the termi-nal left atrial branch (arrow) is seen coursing superiorly to thesubcarinal level above the level of the heart and providing col-lateral flow. This vessel was graded 2. The normal atrial branchis shown (arrowhead).

FIGURE 3. Early (A) and late (B) frames of a right coronary ar-tery injection in the left antrior oblique projection in a patientwho underwent HLT for primary pulmonary hypertension. Thereis marked hypertrophy of multiple distal right atrial branches(arrows), which are heading superiorly toward the subcarinalregion. These numerous small hypertrophied branches are betterseen in the later phase of the angiogram. This is an example ofgrade 3 collaterals.

BRIEF REPORTS 1491

that are more than twice the size of the atrial branches(Figure 3).

Ten of 14 patients (71%) developed coronary tra-cheal collaterals. In 5 patients, collateral vessels orig-inated from the right atrial branch. In another 5 pa-tients both right and left atrial branches hadcollaterals. In 4 patients, no collaterals were seen. Ofthe 10 of 13 patients with serial coronary angiogramsand presence of collaterals, the collateral vessels werenoted at the first annual angiogram. However, progres-sion of the magnitude of the abnormal vessels wasvariable. In 7 patients, there was no change in the sizeof the vessels, but in the other 3 patients the vessel sizeincreased. The patient first seen 3 years after trans-plant had grade 3 collaterals (Figure 3).

Only 1 patient developed airway stenosis, whichwas treated with a tracheobronchial stent. However,this patient died before the first anniversary of trans-plant and therefore did not have a coronary angio-gram. The other 3 patients who did not have collateralvessels on angiography did not develop airway com-plications. No patient had any significant periopera-tive mediastinitis.

• • •Blood supply to the distal trachea and carina is

derived from extensive extrapulmonary anastomosesbetween the bronchial arteries and the vessels supply-ing other mediastinal structures, including the esoph-ageal, thymic, intercostal, thyrocervical, pericardio-phrenic, and coronary arteries.1–4 After single orsequential double-lung transplant without reimplanta-tion of bronchial arteries, the only source of bloodsupply to the donor bronchus is by retrograde perfu-sion from the pulmonary circulation until neovascu-larity of the donor bronchus from collateral circulationestablishes, usually in 3 to 4 weeks.3,4

These collateral channels are normally present, butare very small and are nonfunctional.1 Coronary bron-chial collaterals have been described in patients withcyanotic heart disease or severe chronic obstructivepulmonary disease and aortic stenosis.1,5–7 They canbecome functional in patients with HLT and in thosewith conditions other than transplantation, such asfibrosing mediastinitis. This collateral blood supply tothe donor airway in patients with HLT explains thelower incidence of airway complications comparedwith single- or double-lung transplantation wherethese collateral vessels are divided during surgicaldissection. In patients with no or small coronary col-laterals, other mediastinal branches may provide col-lateral flow, but selective angiography of these vesselsis rarely performed. Perhaps this explains the absenceof any correlation between the presence and/or mag-nitude of coronary collaterals and airway ischemiccomplications.

1. Charan NB, Carvalho PG. Anatomy of the normal bronchial circulatory systemin humans and animals. In: Butler J, ed. Lung Biology in Health and Disease. Vol57. The Bronchial Circulation. New York: Marcel Dekker, 1992:45–77.2. Rees S. Arterial connections of the lung: the inaugural Keith Jefferson lecture.Clin Radiol 1981;32:1–15.3. Kirklin JK, McGiffin D, Young JB. Combined heart and other organ trans-plantation. In: Kirklin JK, ed. Heart Transplantation. New York, NY: ChurchillLivingstone, 2002:771–819.4. Guthaner DF, Wexler L, Sadeghi AM, Blank NE, Reitz BA. Revascularizationof tracheal anastomosis following heart-lung transplantation. Invest Radiol 1983;18:500–503.5. Patterson GA, Cooper JD, Winton TL. Airway complications after double lungtransplantation. J Thorac Cardiovasc Surg 1990;99:14–21.6. Zureikat HY. Collateral vessels between the coronary and bronchial arteries inpatients with cyanotic congenital heart disease. Am J Pediatr Cardiol 1980;45:599–603.7. Bjork L. Anastomoses between the coronary and bronchial arteries. ActaRadiol Diagn 1966;4:93–96.

Incidence of Aspirin Nonresponsiveness Using theUltegra Rapid Platelet Function Assay-ASA

John C. Wang, MD, Denise Aucoin-Barry, RN, Deborah Manuelian, CVT,Rachele Monbouquette, RN, Mark Reisman, MD, William Gray, MD, Peter C. Block, MD,

Elizabeth H. Block, CRC, Marc Ladenheim, MD, and Daniel I. Simon, MD

We report the incidence of aspirin nonresponsivenessin a prospective, multicenter registry (n � 422 pa-tients) to be 23% using the Ultegra Rapid PlateletFunction Assay-ASA, and determined a history of

coronary artery disease to be associated with twicethe odds of being an aspirin nonresponder (oddsratio 2.01, 95% confidence interval 1.189 to 3.411, p� 0.009). Further prospective studies are needed tocorrelate aspirin nonresponsiveness to adverse clini-cal events. �2003 by Excerpta Medica, Inc.

(Am J Cardiol 2003;92:1492–1494)

There is no standard assay to measure platelet func-tion and methods range from the use of urinary

11-dehydrothromboxane B2 levels1 to optical plateletaggregometry.2,3 Subsequently, the incidence of aspi-rin nonresponsiveness varies according to the assay

From the Cardiovascular Division, Brigham and Women’s Hospital,Harvard Medical School, Boston, Massachusetts; Swedish MedicalCenter, Seattle, Washington; Cardiovascular Division, Emory Univer-sity Hospital, Atlanta, Georgia; and Providence St. Joseph MedicalCenter, Burbank, California. Dr. Wang’s address is: Brigham andWomen’s Hospital, Cardiovascular Division, 75 Francis Street, Bos-ton, Massachusetts 02115. E-mail: jwang@partners.org. Manuscriptreceived June 3, 2003; revised manuscript received and acceptedAugust 26, 2003.

1492 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matterThe American Journal of Cardiology Vol. 92 December 15, 2003 doi:10.1016/j.amjcard.2003.08.072