wall deficiency, may result in an increased rate of successful occlusion.“~13

Although speculative, the possible risk of paradoxic embolism through such residual lesions in this popu- lation has been suggested. Whereas the isolated patent foramen ovale, per se, is not considered a cause of peripheral embolism in the adult population, I4 there is evidence that massive, early passage of contrast through a patent foramen ovale during transesophageal echocardiography may predispose to paradoxic em- bolism.15 Yet, the risk of this complication, in the pop- ulation with a patent for-amen ovale is unknown, and whether those patients with residual leaks will require further intervention is speculative.

Supraventricular arrhythmias have not been a sig- nificant adverse event in this small patient cohort, with only 1 patient having a minor dysrhythmia that required no therapy. Although these findings are en- couraging, it is unknown if the long-term incidence of atria1 dysrhythmias will be less than for surgical repair, where the risk is thought to be a combination of disturbed atria1 function secondary to right ven- tricular volume overload and surgical trauma.‘6.‘7

The incidence of device arm fractures was similar to that previously reported, 2,7,8 and Kaplan-Meier analysis suggested that this will continue to increase. Importantly, however, this design flaw, which re- sulted in withdrawal of the device from clinical tri- als, has not resulted in clinical complications, device embolization, or influenced the rate of complete oc- clusion of atria1 defects.

These results indicate that transcatheter occlu- sion of the ASD with the double umbrella device is safe and effective in reducing hemodynamically sig- nificant shunts.

1. King TD, Mills NL. Secundum atrial septal defects: Non-operative closure during cardiac catheterization. JAMA 1976;235:2506-2509. 2. Perry SB, van der Velde ME, Bridges ND, Keane JF, Lock JE. Tramcatheter closure of atria1 and ventricular septal defects. Her-z 1993;18:135- 142. 3. Rao PS, Stderis EB, Hausdorf G, Rey C, Lloyd TR. 13eekman RH, Worms AM, Bourlon F, Onorato E, Khalilullah M, Haddad .I. International experience with secundum atria1 septal defect occlusion by the buttoned device. Am Hean J 1994;128:1022-1035. 4. Redington AN, Rigby ML. Transcatheter closure of interatrial communica- tions with a modified umbrella device. Er Heart J 1994;‘72:372-377. 5. Galal MO, Wobst A, Hatle HL, Schmaltz AA, De Vol KE, Fawzy ME, Abbag F, Fadley F, Duran CM. Pen-operative complications following surgical closure of atria1 septal defect type II in 232 patients-a baseline study. Eur Heart J 1994;15:1381-1384. 6. Rome JJ, Keane JF, Perry SB, Spevak PJ, Lock JE. Double-umbrella closure of attial defects: initial clinical applications. Circulation 1990;82:104-1045. 7. Bridges ND, Hellenbrand W. La&on L, Filiano J, Newburger NW, Lock JE. Transcatheter closure of patent foramen ovale after presumed paradoxical em- bolism. Circulation 1992;86: 1902- 1908. 8. Koike K, Echigo S, Kumate M, Kobayashi T, Isoda T, Ishii M, Ishizawa A, Kamiya T, Kato H. Transcatheter closure of atria1 septal defect with a prototype clamshell septal umbrella: one year follow-up. J Cardioi 1994;24:53-60. 9. Boutin C, Musewe NN, Smallhorn JF, Dyck JD, Kobayashi T, Benson LN. Echocardiographic follow-up of atria1 septal defect after catheter closure by double-umbrella device. Circularion 1993;88:621-627, 10. Meyer RA. Pediatric Echocardiography. Philadelphia: Lea & Febiger 1977:291-294. I I. Reddy SC, Rao PS, Ewenko J, Koscik R, Wilson AD. Echocardiographic

predictors of success of catheter closure of atria1 septal defect with the buttoned device. Am Heart J 1995;129:76-82. 12. Ferreira SM, Ho SY, Anderson RH. Morphologic study of defects of the atria.1 septum within the oval fossa: implications for transcatheter closure of left- to tight shunt. Br Heart J 1992;67:316-320, 13. Rosenfeld HM, van der Velde ME, Sanders SP, Cola” SD, Parness IA, Lock

JE, Spevak PJ. Echocardiographic predictors of candidacy for successful trans- catheter atria1 septal defect closure. Cather Cardiovasc Diagn 1995;34:29-34. 14. Vandenbogeraerde J, De Bleeker J, Decoo D, Francois K. Cambier B, Ber- gen JM, Vandermersch C, De Reuck J, Clement DL. Transoesophageal echo- Doppler in patients suspected of a cardiac source of peripheral emboli. Eur Heart J 1992:13:88-94. 15. Van Camp G, Schulze D, Cosyns B, Vandenbossche JL. Relation between patent foramen ovale and unexplained stroke. Am J Cardiol 1993;71:596-598. 16. Murphy JG, Gersh BJ, McGoon MD, Mair DD, Potter CJ, Ilstrup DM, McGoon DC, Puga FJ, Kirklin JW. Danielson GK. Long-term outcome after surgical repair of isolated atria1 septal defect: follow-up at 27 to 32 years. N Engl J Med 1990;323: 1645- 1650. 17. Bolens M, Friedli 8. Sinus node function and conduction system before and after surgery for secundum atria1 septal defect: an electrophysiologic study. Am J Cardiol 1984;53: 1415- 1420.

Cardiac Output Response to Dynamic Exercise After Atrial Switch Repair for Transposition of the

Great Arteries Eric Page, MD, HBkne Perrault, PhD, Patrice Flare, PhD, Anne-Marie Rossignoi, MD,

Sophie Pironneau, MD, Gcile Rocca, MD and Bernard Aguilaniu, MD

T he impairment in maximal exercise tolerance ob- served in transposition of the great arteries

(TGA) l-6 may be attributed to poor right ventricular function or residual hemodynamic abnormalities, re- sulting in an inadequate exercise-induced increase in stroke volume.2,3,7,* Controversy still exists as to the implications of this impairment in daily tasks. In the only previous study on submaximal exercise re-

From UCP. X, laboratoire de physiopathologie de l’exerclce, Gre- noble, France. Dr. Page’s address is: UCP.X, 4.5 Avenue Marie Rey- noard, 38 100 Grenoble, France. Manuscript received September 13, 1995; revised manuscript received and accepted November

21, 1995.

892 THE AMERICAN JOURNAL OF CARDIOLOGY@ VOL. 77

sponse after TGA repair, a normal cardiac output was observed at 50% of maximal oxygen consump- tion4 Because cardiac output was only determined at a single low exercise intensity level, it is difficult to conclude in favor of normal submaximal cardiac output typical of daily tasks and physical activities. Therefore, we compared the cardiac output response to 2 successive levels of moderate and intense sub- maximal exercise in patients who underwent d-TGA (selected for their good postsurgical success) and their age-matched healthy controls.

. . .

Seven patients (3 boys and 4 girls, aged 10.4 +-

APRIL 15, 1996

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120

110

1 2 3 4 5 6 7 8 9 10 11 12 13

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FIGURE 1. Kinetics of exercise heart rate until exhaustion in pa- tients with transposition of the great arteries (TGA) and in con-

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1.2 years [mean + SEMI ) entered the study 10 + 1 years (range 7 to 15) after Senning (n = 3) or Mus- tard (n = 4) atria1 repair for simple complete d-TGA. The age at surgery was 8.8 + 4 months. All were symptom free, without cardiomegaly, were taking no medication, and led a normal school life. Pulmonary function was normal. Two-dimensional echocardio- graphic evaluation was normal without evidence of moderate or severe impairment of right ventricular function, with a mean right ventricular shortening fraction of 28.6 + 1.2%. Mean systolic time interval and preejection period were 268 + 9 and 123 2 8 ms, respectively. Seven healthy adolescents matched for gender, age, and body surface area ( 10.4 ? 1.2 years; 1.20 & 0.10 m’) served as controls. All chil- dren agreed to take part and informed consent was obtained from the parents.

Children performed a graded exercise test on a treadmill at a constant speed of 5.6 km/hour, with the slope increasing stepwise by 2% every minute until 16% incline and thereafter speed increasing 1 km/hour/mm until exhaustion.6 Ventilator-y and gas exchange parameters were recorded throughout the exercise protocol. Oxygen. consumption (VO,) , car- bon dioxide production (VCO,), ventilatory equiv- alent for oxygen (VE/VOZ) were measured on a breath-by-breath basis using an integrated com- puterized system (Oxycon, Mijnhart, The Nether- lands). Heart rate was calculated from a continu- ous 12-lead electrocardiogram (Marquette Case 12, Milwaukee, Wisconsin). Systolic blood pres- sure was monitored from the right arm at rest and at near-peak end-exercise using a mercury sphyg- momanometer.

In a subsequent evaluation, cardiac output was measured in all subjects at 2 submaximal work- loads selected through intrapolation from the pro- gressive maximal exercise test to correspond to ox- ygen consumption of 20 (E20) and 30 (E30) ml 02.kg-‘.min-‘, respectively. Cardiac output was measured during the last 30 seconds of a 5minute steady-state submaximal workload using the carbon dioxide CO*-rebreathing equilibration method.‘Sub-

FIGURE 2. Oxygen consumption (VOz) and minute ventilation re- sponses at selected heart rates of 120,140,160, and 180 beak/min in patienk with transposition of the great arteries (TGA) and in controls.

jects rebreathed a suitable mixture of CO2 in oxygen (8% to 12%) from a 5liter bag to obtain equilibra- tion of PC02 in the lung-bag system. The mixed ve- nous and arterial CO2 concentrations were derived from the corresponding PCOl values using the COP dissociation curve for oxygenated blood. .Arterial PC02 was estimated from the end-tidal PC& using the algorithm proposed by Jones’ or an arterialized blood sample taken from the ear lobe. Stroke volume and arteriovenous oxygen difference were estimated using oxygen consumption and cardiac output mea- surement. For comparison, values were expressed as cardiac index and stroke index.

All dependent variables are expressed as lmean + SEM. Group comparisons of incremental cardiores- piratory responses were performed using a. 2-way analysis of variance for repeated measures. A Bon- ferroni test was used to compare VE, V02, and heart rate at exercise intensities corresponding to 120, 140, 160, and 180 beats/mm, respectively. A 2 X 2 anal- ysis of variance for repeated measures followed by Bonferroni post hoc analyses was used to compare the cardiac output and stroke volume responses to submaximal exercise. A p value <0.05 was consid- ered statistically significant.

V02max (m102.kg-‘.min-‘) and maximal heart rate (beats/mm) were significantly lower in patients thanincontrols(TGA = 37.6 + 1.4m102~kg-‘~min-’ and 183 + 6 beats/min vs control = 47.8 t 2.5 m102*kg-‘.min-’ and 198 2 16 beats/min) despite true maximal effort in both groups as reflected by the similar levels of V&O, (TGA = 38 ? 2 beats/ min vs control = 39 + 2 beats/min) and circulating lactic acid concentration (TGA = 3.9 + 0.03 mmol/ L vs control = 5 ? 0.5 mmol/L) . Heart rate kinetics from rest to the 10th minute of treadmill tirne were not significantly different between groups (Figure 1). In the control group, however, heart rate contin- ued to increase until maximal exercise was reached 2 minutes later. Ventilatory and oxygen uptake re- sponses at submaximal heart rates of 120, 140, 160, and 180 beats/mm were similar in both groups (Fig- ure 2).

Cardiac output and stroke volume responses to submaximal exercise loads are illustrated in Figures 3 and 4, respectively. A significant increase in car- diac index from the moderate to the more intense exercise load was observed in both groups, although in patients, the magnitude of increase between suc-

BRIEF REPORTS 893

TGA Controls

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FIGURE 3. lndiil cardiac index values measured at exercise intensities ivalent to an oxygen uptake of 20 (E20) and 30

WI mOxg/ min in patiants with traqosition of the great ar- kwies (TGA) and in conlrds. Mean comparisons between E20 and E30 within each group, as well as comparisons between graups at E20 and E30, appear at the bp.

I 100 ,- peo.05 7 - p=NS ----,

I I

EU) E30 EZO E30

cessive levels was half that of controls. Cardiac in- dex values were not significantly different between groups at the lower exercise level (6.9 + 0.5 vs 7.7 t 0.8 litersamin-’ * m’) , but were significantly lower in patients at E30 (7.7 + 0.8 vs 10.3 + 0.5 li- tersemin-’ *m2) (Figure 3). Stroke index was sig- nificantly lower in patients than in controls at both submaximal exercise loads (Figure 4). Moreover, while stroke index remained stable in response to the increased exercise load in controls (63 ? 4 vs 66 + 5 ml - m2), a significant decrease was observed in patients (52 + 3 vs 46 + 4 ml * m2), causing a wid- ening in the initial difference between patients and controls. No significant difference in heart rate was observed at E20 (TGA = 130 If: 4 beats/min vs con- trols = 128 + 2 beats/min) or at E30 (TGA = 166 + 6 beats/min vs controls = 159 ? 5 beats/min).

. . . Results from the present study confirm that in asymptomatic patients with successful atrial correc- tion of TGA, exercise tolerance is reduced 2 10 years after surgery, and an impairment in stroke volume is observed at both moderate and higher submaximal exercise intensities. Maximal oxygen uptake values measured in the present study are similar Is3 or slightly higher4*5 than those previously reported in adolescents after Mustard or Senning correction, but lower compared with healthy control subjects. This can mainly be explained by 2 isolated or combined mechanisms, namely an impaired chronotropic re- sponse to exercise and a right ventricular dysfunc- tion. Cardiac arrhythmias are common after atrial switch repair, lo-l3 and the usual mechanism is dam- age to the sinoatrial node, with subsequent reduction in sinoatrial automacity at rest l4 and during exer- cise.5*‘0 In the present study, the sinus response was

FIGURE 4. Individual stroke index values measured at exercise intensities u’mlent to an oxygen uptake of 20 (EZO) and 30 (E30) m&>g/ min in patients with corrected transposition of the great arteries (TGA) and in controls. Mean comparisons between E20 and E30 within each group, as well as comparisons between groups at E20 and E30, appear at the top.

normal at each stage of the treadmill test until an exercise time of 10 minutes (Figure 1). Conse- quently, in accordance with results previously re- ported by Paricon et al, 5 the present findings suggest that the lower V02max of patients is not exclusively tpe result of a chronotropic impairment. In fact, V02max in our patients was reduced 22% compared with control values, whereas the difference in con- trols for maximal heart rate was only 13%. Using radionuclide ventriculography at rest and during ex- ercise, an abnormal ejection fraction response to ex- ercise was previously reported in >60% of asymp- tomatic patients who underwent operation for d-TGA, suggesting a decrease in myocardial reserve of the right ventricle. 7.8,‘7 Because ejection fraction is only an index of ventricular co&.actility not in- dependent of ventricular afterload, cardiac output was measured in the present study to better reflect the integration of both central (cardiac output) and peripheral (arteriovenous oxygen difference) ele- ments of the circulatory function. The exercise-in- duced increase in cardiac output is generally deter- mined by concurrent increases in both heart rate and stroke volume for exercise intensities up to approx- imately 50% V02max, beyond which stroke volume remains unchanged and heart rate alone increases.18

At the lower exercise load corresponding to 53% of V02max in our patients, cardiac index was not significantly different from controls, which is in agreement with the previous report at 50% V02max.4 However, in patients, the magnitude of increase in cardiac index from E20 to E30 was half that of controls. This abnormal increase in cardiac index in patients suggests a compensatory reliance on peripheral oxygen extraction. Because heart rate values were not significantly different between groups at E30 (TGA = 166 ? 6 beats /min vs controls

894 THE AMERICAN JOURNAL OF CARDIOLOGY” VOL. 77 APRIL 15, 1996

= 159 + 5 beats/mm), the impairment in cardiac output was attributed to a limitation in the ventricular output response to exercise as reflected by the de- crease in stroke index between E20 and E30. This abnormal response could be ascribed to an impair- ment in contractile function as previously shown. The increase in stroke volume from rest to approximately 50% of VO,max is mainly dependent on an increase in ventricular preload.18 In the present study, stroke index was lower in patients at E20, suggesting that an impairment in, pulmonary venous return associated with the presence of the intraatrial baffle may be a contributing factor.19,20 A significant decrease in right ventricular end-diastolic volume index has previously been reported in patients surgically corrected for TGA in response to peak exercise I9 as well as for an ex- ercise load equivalent to a heart rate of 154 beats/ min.2o It is thus not unlikely that a similar limitation exists in our population.

In conclusion, results from the present study in- dicate an impairment in systemic ventricular out- put at exercise loads equivalent to recreational ac- tivities. A compensatory increase in peripheral oxygen extraction may be adequate to maintain VO, in the presence of an impaired cardiac output during exercise. Although this compensatory mech- anism could provide adequate adaptation during brief bouts of moderate exercise, it remains to be seen whether this would be the case with matura- tion or for prolonged exercise when cardiovascular contraints are more important.

1. Bowyer JJ, Busst CM, Till JA. Lincoln C, Shineboume EA. Exercise ability after Mustard’s operation. Arch Dis Child 1990;65:865-870. 2. Ensing GJ, Heise CT, Driscoll DJ. Cardiovascular response to exercise after the Mustard operation for simple and complex transposition of the great vessels. Am J Car&l 1988;62:617-622. 3. Mathews RA, Fricker FJ, Beerman LB, Stephenson RJ, Fischer DR, Neches WH, Park SG, Lenox CC, Zuberbuhler JR. Exercise studies after the Mustard operation in transposition of the great arteries. Am J Cardiol 1983;5 1: 1526- 1529.

4. Musewe NN, Reisman J, Benson LN, Wilkes D, Levison H, Freedom RM, Tmsler GA, Canny GJ. Cardiopulmonary adaptation at rest and during exercise 10 years after Mustard atria1 repair for transposition of the great arteries. Cir-

culation 1988;77:1055- 1061. 5. Paridon SM, Humes RA, Pinsky WW. The role of chronotropic impairment during exercise after the Mustard operation. J Am Co0 Cardiol 1991;17:729- 732. 6. Reybrouck T, Dumoulin M, Van der Hauwaert LG. Cardiorespiratory exer- cise testing after venous switch operation in children with complete transposi- tion of the great arteries. Am J Cardiol 1988:61:861-865. 7. Murphy JH. Barlay-Kovach MM, Mathews RA, Beerman LB, Park SC, Neches WH, Zuberbuhler JR. Rest and exercise right and left ventri#zular func- tion late after the Mustard operation: assessment by radionuclide ventriculog- raphy. Am J Cardiol 1983;51:1520- 1525. 8. Parrish MD, Graham TP, Bender HW, Jones JP, Patton J, Partal” CL. Ra- dionuclide angiographlc evaluation of right and left ventricular funuion during exercise after repair of transposition of the great arteries. Circularion 1983; 67:178-182. 9. Jones NM. Clinical exercise testmg. 3rd ed. Philadelphia: WB Saunders, 1988;186-207. 10. Hesslem PS, Gutgessel HP, Gillette PC, McNamara DG. Exercise assess- ment of sinoatrial node function following the Mustard operation. ,4m Hear? 3 f982:103:351-357. 11. Beerman LB, Neches WH, Fricker FJ, Mathews RA, Fischer DR, Park SC, Lenox CC, Zuberbuhler JR. Arrhythmias in transposition of the greeat arteries after Mustard operation. Am J Cardiol 1983:51:1530-1534. 12. Vetter VL, Tanner CS, Horowitz LN. Electrophysiologic consequences of the Mustard repair of d-transposition of the great arteries. J Am ColI Cardiol 1987;10:1265-1273. 13. Gillette PC, Kugler JD, Garson A, Gutgessel HP, Duff DF, McNamara DG.

Mechanisms of cardiac arrhythmias after the Mustard operation for transposition of the great arteries. Am J Cardiol 1980;45: 1225- 1230. 14. Graham TP, Atwood GF, Boucek RJ, Boerth RC, Bender HW. Abnormal- ities of right ventricular function following Mustard’s operation for transposi- tion of the great arteries. Circulation 1975;52:678-684. 15. Godman MJ, Friedli B, Pastemac A, Kidd BSL. Tmsler GA, Mustard WT. Hemodynamic studies in children four to ten years after the Mustar’d operation for transposition of the great arteries. Circulation 1976:53:532-538. 16. Turina MI, Siebemann R, Von Segesser L, SchGnbeck M, Senning A. Late functional deterioration after atria1 correction for transposition of the great w- teries. Circulation 1989;8O(suppl 1):1-162-l-167. 17. Ramsay JM. Venables AW, Kelly MI, Kalff V. Right and left ventricular function at rest and with exercise after the Mustard operation for transposition of the great arteries. Br Heart J 1984:51:364-370. 18. Higginbotham MB, Morris KG, Williams RS. Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circ Res 1986;58:281-291. 19. Benson L, Bonet J, McLaughlin P, Olley PM, Feiglin D, Dmck M, Tmsler G. Rowe RD, March J. Assessment of right ventricular function during supine bicycle exercise after Mustard’s operation. Circulation 1982;65:1052- 1059. 20. Peterson RJ, Franch RH, Fajman WA, Jones RH. Comparison of cardiac function in surgically corrected and congenitally corrected transposition of the great arteries. J Thorac Cardiovasc Surg 1988;96:227-236.

The Varying Evolution of Friedreich’s Ataxia Cardiomyopathy

Franc0 Casazza, MD, and Mario Morpurgo, MD

T he various electrocardiographic (ECG) altera- tions in patients with Friedreich’s ataxia are well

described in published reports.1-4 Echocardiography (echo) has shown that the left ventricle is very often characterized by either concentric or asymmetric hy- per-trophy, with continuing normal systolic func- tion.5-8 Conversely, far fewer patients have evidence of hypokinetic cardiomyopathy with normal or in-

From the Division of Cardiology, San Carlo Hospital, via Pio 2”, 3, 20153 Milan, Italy. Dr Morpurgo’s address is: via Boccaccio 24, 201 23, Milan, ltol Manuscript received May 24, 1995; revised manuscript receive cr and accepted November 24, 1995.

creased left ventricular (LV) wall thickness associ- ated with severe reduction in the indexes of LV sys- tolic function.‘,” The debate is open as to whether the hypokinetic form represents the terminal stage of an initially hypertrophic cardiomyopathy, as specu- lated by Gottdiener et al,” or is a separate entity characterized mainly by cardiac fibrosis, termed ‘ ‘dystrophic,” as claimed by Child et a1.4 Hawley and Gottdiener lo followed 3 of 10 patients with Frie- dreich’s ataxia, who initially had the smallest LV dimensions, and 5 years later developed dilatation of the left cavity with decreasing fractional shortening and stable or decreasing ventricular wall thickness

BRIEF REPORTS 895