Volume 130, Number 1 American Heart Journal Freimark et al.

tation increases were discerned in this study. The younger the age and smaller the diameter of the aor- tic isthmus and coarctation segment (both before and after angioplasty), the greater the change for reco- arctation. Knowledge of risk factors may help in the selection of patients for angioplasty of native coarc- tations. Minimizing the number of risk factors or avoiding them may help reduce the chance for reco- arctation after balloon angioplasty.

In conclusion, the data from this study confirm that the previously identified risk factors for reco- arctation are valid in predicting recoarctation after balloon angioplasty and may help in the selection of patients for balloon therapy of native coarctations.

We t h a n k Drs . O. Galal , M. K. Mardin i , L. Solymar , M. K. Thapa r , a n d A. D. Wilson.

REFERENCES 1. Lababidi ZA, Daskalopoulos DA, Stoeckle H Jr. Transluminal balloon

coarctation mlgioplasty: experience with 27 patients. Am J Cardiol 1984;54:1288-91.

2. Wren C, Peart J, Bain H, Hunter S. Balloon dilatation of unoperated aortic coarctation: immediate results and one year follow-up. Br Heart J 1987;58:369-73.

3. Beekman RH, Rocchini AP, Dick M II, Snider AR, Crowley DC, Serwer GA, Spicer RL, Rosenthal A. Percutaneous balloon angioplasty for na- tive coarctation of the aorta. J Am Cell Cardiol 1987;10:1078-84.

4. Morrow WR, Vick GW, II, Nihill MR, Rokey R, Johnson DL, Hedrick TD, Mullins CE. Balloon dilatation of unoperated cuarctation of the aorta: short-and intermediate terra results. J Am Cell Cardiol 1988; 11:133-8.

5. Suarez de Lezo J, Sancho M, Pan M, Romero M, Olivera C, Lupue M. Angiographic follow-up after balloon angioplasty for coarctation of the aorta. J Am Cell Cardiol 1989;13:689-95.

6. Fontes V-F, Esteves CA, Brago SLM, da Silva MVD, de Silva MAP, Sousa JEMR, de Souza AM. It is valid to dilate native aortic coarcta- tion with a balloon catheter. Int J Cardiol 1990;27:311-6.

7. Redington AN, Booth P, Shore DF, Rigby ML. Primary balloon dilata- tion of coarctation of the aorta in neonates. Br Heart J 1990;64:277-81.

8. Minich LL, Beekman RH, Rocchini AP, Heidelberger K, Bove EL. Sur- gical repair is safe and effective after unsuccessful angioplasty of na- tive coarctation of the aorta. J Am Cell Cardiol 1992;19:389-93.

9. Lababidi Z. Percutaneous balloon coarctation angioplasty: long-term results. J Intervent Cardiol 1992;5:57-11.

10. Rao PS, Thapar MK, Kutayli F, Carey P. Causes ofrecoarctation after balloon angioplasty ofunoperated aortic coarctation. J Am Cell Cardiol 1989;13:109-15.

11. Rao PS. Transcatheter treatment of pulmonary stenosis and coarcta- tion of the aorta: experience with percutaneous balloon dilatation. Br Heart J 1986;56:250-8.

12. Rao PS. Balloon angioplasty for coarctation of the aorta in infancy. J Pediatr 1987;110:V13~8.

13. Rao PS, Najjar HN, Mardini MK, Solymar L, Thapar MK. Balloon an- gioplasty for coarctation of the aorta: immediate and long-term results. AM HEART J 1988;115:657-64.

14. Rao PS, Thapar MK, Galal 0, Wilson AD. Follow-up results of balloon angioplasty of native coarctation in neonates and infants. AM HEART J 1990;120:1310-4.

15. Rao PS, Carey P. Remodeling of the aorta following successful balloon coarctation angioplasty. J Am Cell Cardiol 1989;14:1312-7.

Improved left atrial transport and function with orthotopic heart transplantation by bicaval and pulmonary venous anastomoses

D o v F r e i m a r k , M D , a L a w r e n c e S . C . C z e r , M D , a I v a n A l e k s i c , M D , b C o r d B a r t h o l d , R D C S , R C V T , a

D a n A d m o n , M D , a A l f r e d o T r e n t o , M D , b C a r l o s B l a n c h e , M D , b M a r i o V a l e n z a , M D , b a n d

R o b e r t J . S i e g e l , M D a Los Angeles, Calif.

From the Divisions of aCardiology and bCardiothoracic Surgery, Cedars-Si- nai Medical Center, and the University of California-Los Angeles School of Medicine.

Supported in part by the Save-A-Heart Foundation (Los Angeles); Deutsche Forschungsgemeinschaft (DFG) grant A1 381/1-1 (Bonn, Germany); and Grand Sweepstakes Foundation (Los Angeles).

Received for publication July 26, 1994; accepted Nov. 16, 1994.

Reprint requests: Lawrence S.C. Czer, MD, Division of Cardiothoracic Sur- gery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 6215, Los Angeles, CA. 90048-1865.

Copyright © 1995 by Mosby-Year Book, Inc. 0002-8703/95/$3.00 + 0 4]1/68795

Orthotopic heart transplantation (OHT) with bicaval and pul- monary venous anastomoses avoids the large atrial anasto- moses of the standard biatrial technique. To determine whether the bicaval technique improves atrial performance, we used Doppler echocardiography to study 13 patients with bicaval OHT, 15 with biatrial OHT, and 8 normal subjects. All were in sinus rhythm and free of rejection. Left atrial size, transmitral (M) and late diastolic (A) mitral flow velocity in- tegrals were measured. Atrial transport (A/M, %) and atrial ejection force (kilodynes, calculated from peak A-wave ve- locity and mitral orifice area) were assessed. Left atrial dimensions in the bicaval (4.3 + 0.5 cm) and biatrial groups

121

July 1995 122 Freimark et al. American Heart Journal

(4.9 + 0.9 cm) were larger than in controls (3.3 + 0.8 cm, p< 0.05). Left atrial transport (37% + 12% and 35% ± 12%) and ejection force (14.1 ± 6.9 kdyne and 10.2 ± 7.8 kdyne) were similar in the bicaval group and controls (p not signif- icant) but were significantly lower in the biatrial group (20% ± 19% and 3.6 ± 4.0 kdynes, p < 0.05). The bicaval and pulmonary venous technique of OHT produces more phys- iologic atrial function compared with the biatrial technique as evidenced by greater atrial ejection force and more nor- mal atrial transport. (AM HEART J 1995;130:121-6.)

H e a r t t r ansp l an t a t i on is a well-establ ished t h e r a p y for pa t ien ts wi th end-s tage h e a r t failure. The surgi- cal t echnique used by most centers for this operat ion has been essent ia l ly una l t e red since its descript ion by Lower and S h u m w a y in 1960.1 The technique in- volves anas tomosis of the donor a t r i a to those of the recipient , leaving a large cuff of the recipient 's r ight and left a t r i a and resul t ing in long atr ia l su tu re lines wi th increased r i sk of th rombus format ion 2 and a subs tan t ia l incidence of electric conduction abnor- mali t ies. 3 The a l te red atr ia l geomet ry fu r t he r leads to dis tor t ion of the a t r iovent r icu la r annuli , causing var ious degrees of a t r iovent r icu la r va lvu la r regurgi- tat ion. 2 Doppler echocardiographic studies have shown reduced diastolic t r an smi t r a l flow though t to be caused by asynchronous contract ion of the recip- ient and donor a t r ia l r emnan t s . 4

In recent yea r s a modified surgical t echnique t e r m e d total orthotopic hea r t t r ansp l an t a t i on has been introduced. 5 This modification of the s t anda rd biatr ia l t echnique uses bicaval and pu lm o n a ry venous anas tomoses af ter near ly complete excision of the recipient 's atr ia. The potent ia l advan tage of this technique is be t t e r p reserva t ion of the a n a t o m y and funct ion of the a t r i a of the t r ansp lan ted hear t . Previous studies by our group 6, 7 have shown less pos topera t ive a t r iovent r icu la r valve regurgi ta t ion, fewer symptomat ic b radycard ias requi r ing perma- n e n t pa c e ma ke r implanta t ion , and improved sur- vival wi th the technique of bicaval and pu lm o n a ry venous anastomoses . The purpose of this s tudy was to assess left a t r ia l funct ion a n d t r anspor t by Dop- pler echocardiography in cardiac t r ansp l an t pa t ien ts and to compare these echocardiographic pa r am e te r s in pa t ien ts t r ea t ed by the bicaval and pu lmona ry venous anas tomot ic technique wi th the same param- e ters in pa t ien ts t r ea t ed by the bia t r ia l anas tomot ic technique.

METHODS Patients. Eight healthy volunteers with no history of

systemic hypertension or cardiac or peripheral vascular disease were studied and served as controls. The 7 men and

i woman had a mean age of 30.1 +- 5.4 years (range 28 to 38 years), similar to the heart donors (mean age 26.1 -+ 9.1, range 9 to 44 years; p = NS). We studied patients after orthotopic heart transplantation who met the following criteria: (1) right-heart catheterization and endomyocar- dial biopsy within the previous 24 hours; (2) no evidence of rejection on an endomyocardial biopsy; (3) minimal or no mitral regurgitation by Doppler echocardiographic study performed >2 months postoperativelyS; (4) presence of normal sinus rhythm of the donor heart on electrocardio- graphic tracing; and (5) left ventricular ejection fraction (LVEF) >-45% by two-dimensional echocardiography. These criteria enabled accurate assessment of atrial func- tion in the absence of clinically significant rejection, atrio- ventricular valve regurgitation, or left ventricular dys- function.

By these criteria, 28 of 117 patients who received trans- plants between December 1988 and September 1993 qual- ified for this study. There were 23 men and 5 women. We reviewed the hospital and follow-up records and donor charts for these patients with attention to the age of the donors and recipients, recipient pulmonary vascular resis- tance and ejection fraction, dosage of dopamine support before procurement, operative ischemic time, intensive care unit (ICU), and total hospital stay after transplanta- tion.

Surgical technique. The standard technique of ortho- topic heart transplantation with biatrial anastomoses was used in the first 15 patients (December 1988 to August 1991). The subsequent 13 patients underwent heart trans- plantation by bicaval and pulmonary venous anastomoses as described by Dreyfus et al. 5 and modified by our group 6, 7 (October 1991 to September 1993). Donor heart preserva- tion consisted of hypothermic cardioplegic arrest after perfusion with St. Thomas Hospital solution (n = 14) or Stanford solution (n = 13) and hypothermic storage (4 ° C). All patients received an induction course of murine mono- clonal antibody muromonab-CD3 (Orthoclone-OKT3; Ortho Biotech, Raritan, N.J.) for 10 to 14 days. Triple drug immunosuppression consisting of cyclosporine A, azathio- prine, and prednisone was used.

Endomyocardial biopsy and right-heart catheterization were performed in all patients. Patients were excluded from the study if they had significant cellular rejection (grade >-IB) according to the International Society for Heart and Lung Transplantation criteria 9 or humoral re- jection as diagnosed by histologic findings and positive im- munofluorescence for immunoglobulins and complement.l° During right-heart catheterization, mean right atrial, pul- monary arterial, and mean pulmonary capillary wedge pressures and cardiac output were measured and cardiac index was calculated. Heart rate and blood pressure were recorded during the procedure.

Echocardiographic studies. Transthoracic two-dimen- sional Doppler echocardiographic examinations were per- formed with the patient in the left lateral decubitus posi- tion by using a Hewlett-Packard Sonos 1000 machine with either a 2.5 or a 3.5 MHz phased-array transducer.

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American Heart Journal Fre imark et al. 123

Table I. Demographic and preoperative characteristics

Biatrial Bicaval (n = 15) (n = 13) p Value

Age (yr) 56.4 ± 8.2 53.2 ± 8.5 0.32 Gender 0.10

Men 10 (67%) 12 (92%) Women 5 (33%) 1 (8%)

Left ventricular ejection fraction before transplant (%) 18.3 _+ 3.8 16.8 ± 5.2 0.39 Pulmonary vascular resistance before transplant 3.4 ± 2.1 2.5 ± 1.5 0.19

(Wood's units) Donor age (yr) 27.4 ± 7.4 28.9 _+ 10.3 0.65 Preprocurement dopamine dose in donors (pg/kg/min) 6.3 ± 5.1 5.8 _+ 2.9 0.76 Ischemic time (min) 131 + 34 161 _+ 29 0.02 Length of stay (day)

Intensive care unit 5.8 ± 2.3 6.0 _+ 3.6 0.86 Total 19.3 ± 5.2 18.9 ± 7.9 0.89

Rejection episodes per patient 1.13 ± 0.64 1.15 ± 0.99 0.39 Time interval between transplant and echo-study (too) 33.4 ± 15.8 8.3 ± 6.7 0.0001

Values are expressed as m e a n _+ SD.

Table I I . Echocardiographic and hemodynamic parameters

LA size L V E F L V mass PA pressure PCW pressure Cardiac index Stroke index Group (cm) (%) (gm) (ram Hg) (ram Hg) (L / min / m 2) (ml / min / m 2)

Biatrial (n = 15) 4.59 ± 0.94* 59.0 _+ 9.4 201 ± 46.6 32 _+ 11 11 ± 4 2.76 ± 0.88 34.4 _+ 9.5 Bicaval (n = 13) 4.32 _+ 0.45* 53.7 ± 6.5 217 ± 56.4* 29 ± 7 12 -+ 5 2.96 ± 0.67 33.3 ± 8.3 Control (n = 8) 3.33 ± 0.79 58.3 ± 3.8 157 _+ 36.5 . . . .

LA, Lei~ atrial; LV, lefL ventricular; EF, ejection fraction; PA, pulmonary arterial systolic; PCW, pulmonary capillary wedge. *p < 0.05 compared with controls.

Paras ternal long and short axis and apical four- and two- chamber views 11 were obtained, and hard copy recordings were made at a paper speed of 25 to 50 mm/sec. In all studies the technician and the evaluat ing physician were blind to the surgical technique. Left atrial dimension was determined from M-mode (parasternal long-axis view). Left ventr icular mass, 12 end-systolic, and end-diastolic volume and ejection fraction were calculated by using a bi- plane ellipse method. 13 Transmi t ra l flow velocity was re- corded by pulsed Doppler between the tips of the mit ra l leaflets from the apical four-chamber view with the pat ient in the left lateral position.

The total diastolic (M) and late diastolic (A, in centime- ters) t ransmi t ra l flow velocity integrals were measured by p lanimetry after manua l tracing of the area under the mi- tral velocity curve with a trackball cursor by using soft- ware available on the machine. A min imum of 20 consec- utive Doppler waveforms were examined to obtain the largest A wave of a well-defined, technically adequate mi- tral velocity curve. The largest A wave was chosen to pro- vide the best separation of active from passive atrial con- traction and to provide a physiologic basis of comparison when asynchronous contraction of the atr ia may occur.

Atrial t ranspor t was defined as the ratio of the late di- astolic and total diastolic t ransmi t ra l flow velocity inte-

grals (A/M, %). Atrial ejection force (AEF) was calculated from the formula14: AEF = 0.5 × p × mitral orifice area x (peak A velocity squared), where p is the density of blood (1.06 gndcm 3) and AEF is measured in uni ts of dynes (gin x c mx sec-2). The mitral orifice was assumed to be circular and estimated from the mitral annu lus diameter as measured from the apical four-chamber view at end di- astole. The mitral orifice area was calculated as ~r 2, where 2r was the diameter of the mitral annulus .

Statistics. One-way analysis was used to test the differ- ences among the two surgical groups and the controls. Calculations were performed by the SAS procedure 15 ANOVA. When the overall statistic was significant (p < 0.05), pairwise tests were made by using the Bonfer- roni method to adjust for multiple comparisons. Two-way comparisons were performed with the two-sample t test for continuous data and Fisher's exact test or Pearson chi- squared test for categoric data. The data are displayed as mean _+ SD or percentage where appropriate.

RESULTS Patient characteristics and clinical course (Table I).

A m o n g t he 28 s t u d y p a t i e n t s , 15 h a d t he s t a n d a r d t e c h n i q u e of or thotopic h e a r t t r a n s p l a n t a t i o n w i t h b i a t r i a l a n a s t o m o s e s a n d 13 h a d b i c a va l a n d p u l m o -

July 1995 124 Freimark et al. American Heart Journal

Fig. 1. C•mparis•n •fD•pp•er parameters in heart transplant recipients with standard biatrial technique (n = 15, black bar) or with bicaval and pulmonary venous anastomotic technique (n = 13, gray bar), and in norma] controls (n = 8, white bar). Values are mean _+ SD. A, Atrial ejection force (AEF); B, atrial trans- port (AIM percentage); C, late diastolic flow integral (total A).

nary venous anastomoses (hereafter abbreviated as bicaval). As shown in Table I, there were no signif- icant differences in age or gender of recipients, age of donors, or preprocurement inotropic support with dopamine in the donors. The pretransplant clinical characteristics of the recipients, including left ven- tricular ejection fraction and pulmonary vascular resistance, were similar.

Ischemic time was longer for the bicaval group than for the biatrial group. Postoperative recovery times were similar as reflected by the length of stay in the intensive care unit and the total hospital stay after surgery. The time interval between heart transplantation and the echocardiographic exami- nation was significantly longer for the biatrial group compared with the bicaval group (p = 0.0001). De- spite the longer time elapsed between the operation and the echocardiographic study in the biatrial group, the number of rejection episodes per patient was similar in the two surgical technique groups (1.13 in the biatrial technique group vs 1.15 in the bicaval and pulmonary venous technique; p = NS).

Echocardiograpbic and hemodynamic variables. Ta- ble II lists the echocardiographic parameters for the two surgical technique groups and the control group and the hemodynamic variables of both recipient groups. There was no significant difference in left ventricular ejection fraction among the three groups, nor was there any difference in the hemodynamic parameters of pulmonary arterial systolic pressure, mean capillary wedge pressure, cardiac index, and stroke index between the two surgical groups.

However, the mean left atrial size of both recipient groups was larger than in the control group (p < 0.05). The recipient groups did not differ in left atrial size, although there was a tendency for a larger left atr ium in the biatrial group. Left ventricular mass was similar in the bicaval and biatrial groups but was higher in the bicaval group than in the controls (p < 0.05).

Left atrial function was assessed by the atrial t ransport (A/M, percentage), atrial ejection force (AEF, kilodynes), and late diastolic flow integral (A, centimeters; Fig. 1). There was significantly greater atrial t ransport and atrial ejection force in the bicaval group compared with the biatrial group (37% -+ 12% and 14.1 +_ 6.9 kdynevs 20% + 19% and 3.6 ,+ 4.0 kdyne,p < 0.05 for each); the values for the bicaval group were comparable with the control group (35% _+ 12% and 10.2 .+ 7.8 kdyne, Fig. 1, A and B). The late diastolic flow integral was signifi- cantly lower in the biatrial group than in the controls (2.8 .+ 2.5 cm vs 6.6 .+ 2.6 cm; p < 0.05; Fig. 1, C). However, this parameter was similar for the bicaval group when compared with the controls (4.9 +_ 1.9 cm vs 6.6 _+ 2.6 cm; p = NS).

DISCUSSION

This is the first study to demonstrate that, in com- parison with the biatrial anastomosis, the bicaval and pulmonary venous anastomotic technique of orthotopic heart transplantation improves atrial contraction as evidenced by greater atrial ejection force and atrial transport (Fig. 1). These findings in- dicate that substitution of the bicaval for the stan- dard biatrial technique results in improved left atrial function in the transplanted heart that is compara- ble to function found in control subjects.

Our findings are consistent with previous studies, 16 which have demonstrated a significant difference in atrial performance between normal controls and that of patients undergoing heart trans- plantation with the biatrial technique. In our study, the late diastolic transmitral flow integral was sig- nificantly lower with the biatrial technique than in controls (Fig. 1). In patients with biatrial anasto- motic technique, Cresci et al.17 measured the donor and recipient components of the left atr ium and the relative contribution of each component to atrial function. By using transthoracic echocardiography

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American Heart Journal Freimark et al. 125

with automatic boundary detection by acoustic quan- tification, the recipient and donor portions of the atrial area were found to have a ratio of 3:2. The mean absolute change in area from mid to late dias- tole (atrial contraction) was markedly reduced in the recipient component compared with the donor por- tion of the left atrium. Thus although the recipient component of the atr ium was larger, it contributed negligibly to atrial function. As a consequence, the overall contractility of the left atr ium was reduced. In addition, spontaneous echocardiographic contrast and thrombi have been demonstrated in the atria of t ransplant recipients by transesophageal echocardi- ography despite normal ventricular function and mitral valve opening, is These findings may be ex- plained by slower blood flow resulting from atrial enlargement and asynchronous contraction of the donor and recipient atria, is Spontaneous echocar- diographic contrast and atrial thrombi may be less likely to occur with the bicaval and pulmonary venous anastomotic technique because of the smaller atrial size and improved atrial function.

The atrial ejection force, first described by Man- ning et al., 14 is relatively independent of atrial pre- load and afterload. It is therefore a useful measure of atrial contractility. We used this parameter in ad- dition to atrial t ransport to minimize the impact of changes in loading conditions that may occur after heart transplantation 19 as a result of volume shifts, use ofvasodilator drugs, and other factors. To reduce the influence of diastolic compliance changes, we studied only those patients who were >2 months past t ransplant and free from rejection.

Although greater atrial contractility should pro- duce improved ventricular performance, the result- ing increment may be low in the presence of normal ventricular function and thus not detectable at rest or with smaller population sizes. Accordingly, hemo- dynamic parameters did not differ significantly be- tween the two recipient groups under resting condi- tions (Table II). However, the atrial contribution to ventricular function may be more substantial under conditions ofventricular dysfunction or stress. Thus the bicaval and pulmonary venous anastomotic tech- nique has the potential to improve exercise perfor- mance after hear t transplantation. The exercise performance of patients who have received trans- plants is significantly reduced in patients whose transplants were performed by the biatrial tech- nique compared with normal controls, 2° mainly be- cause of reduction in ventricular compliance. 21 The bicaval and pulmonary venous anastomotic tech- nique may also improve cardiac function during re- jection or in other conditions of reduced ventricular

compliance 22 and may reduce pressor dependence early postoperatively and in patients who receive small donor hearts. Fur ther studies are needed to confirm the potential advantages of this new surgi- cal technique and may include investigation of max- imal oxygen consumption or exercise hemodynamics.

The time interval from transplantation to echocar- diographic study differed between the two recipient groups. The longer time interval could potentially influence atrial function. However, the present study shows no significant difference in atrial performance between controls and patients with the bicaval and pulmonary venous anastomotic technique. Previous studies 4, 23 have demonstrated reduced atrial func- tion as early as 2 to 6 months after transplant with the biatrial technique. Because our study demon- strated similar atrial function between the bicaval and pulmonary venous anastomotic technique group and controls at a mean of 8 months after transplan- tation, it is unlikely that the difference between the two recipient groups is caused only by the longer time interval elapsed from transplantation to echocardio- graphic examination in the biatrial technique group. In addition, despite the temporal difference between transplantation and the Doppler echocardiographic study, the number of cardiac rejection episodes was the same in the two groups of transplanted patients.

Left atrial function has been compared in heart and heart-lung transplant recipients. 16 The ratio of active to passive left atrial flow was significantly less in heart t ransplant recipients than in heart-lung re- cipients or normal controls. The preserved structural integrity of the left atrium in heart-lung recipients and normal controls may explain this finding. Sim- ilarly, the improved atrial function with a bicaval and pulmonary venous anastomotic technique may be the result of better preservation of atrial struc- tural integrity comparable to that achieved with heart-lung transplantation or in normal controls.

Use of the new surgical technique simplifies ECG interpretation after heart transplantation because the recipient sinus node has been removed and therefore only one P wave is produced. No further electrophysiologic observations have been made, and this can be a focus of future studies. Only one case of superior vena cava stenosis has been noted in our series. Thus the bicaval and pulmonary venous anastomotic technique as assessed by a t r ia l trans- port and ejection force provides more physiologic atrial function than the standard method of cardiac transplantation. The improved atrial function with the bicaval technique has the potential to produce better long-term performance of the cardiac al- lograft.

July 1995 126 Freimark et al. American Heart Journal

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