hemodynamic responses to isolated increments in heart rate by atrial pacing after a fontan procedure

I I l l ] I [ I I I I I I I

H e m o d y n n c responses to isolated i n c r m n t s in heart rate by atrial pacing after a Fontan

procedure

The physiologic role of the right ventricle has long been a subject of interest to physiologists. The Fontan operation provides a human model for studying the circulation in series devoid of a subpulmonic right ventricle. The hemodynamic response to isotonic exercise in this setting has been established, end differs appreciably from normal. However, the physiologic response to an increase in heart rate (atrial pacing) as an isolated variable has not been examined and compared to atrial pacing in hearts with two concordant subarteeisi ventricles. Accordingly, we compared the supine bicycle exercise response to rate-equivalent right atrial pacing in nine patients after atriopulmonary anastomoses (the Fontan operation) for eingie ventricle or tricuspid atresia. Cardiac index increased 77% with exercise (rest 2.6 L/min/m=; exercise 4.6 L/min/m =) but decreased 12% with atrial pacing (rest 2.5 L/rain/m=; pacing 2.2 L/min/m=). Pulmonary arterial oxygen saturation declined significantly during exercise (rest 68%; exercise 31%) and during atrial pacing (control 72%; pacing 64%). The mean increment in pulmonary arterial pressure was 1.3 times greater with exercise (rest 14 mm Fig; exercise 20 m m Hg) than with pacing (control 12 mm Hg; pacing 16 mm Hg). Peak systemic arterial systolic pressure increased 14% with exercise but was unchanged by pacing. Systemic and pulmonary vascular resistances fell with exercise but changed insignificantly during atrial pacing. Stroke volume rose slightly with exercise but fell significantly with pacing. Our patients with an atriaFdependtnt pulmonary circulation and a subaorti¢ left ventricle had hemodynamic responses to atrlei pacing that were similar to the responses of normal subjects with two concordant subarterial ventricles, indicating the dispensability of the right ventricle when heart rate is examined as an isolated variable. Conversely, the hemodynamic response to isotonic exercise in an atriaFdepend|mt pulmonary circulation underscores the role of a subpulmonic right ventricle in preserving the exercise response. The difference in responses between atrial pacing and dynamic exercise in our patients was similar in direction but quantitatively blunted when compared to normal subjects with two concordant subarterial ventricles in series. (AM HEART J 1988;115:837.)

Gerald Barber, M.D., Thomas Di Sessa, M.D., John S. Child, M.D., Joseph K. Perloff, M.D., Hillel Laks, M.D., Barbara L. George, M.D., and Roberta G. Williams, M.D. Los Angeles, Calif.

The role of the right ventricle in the circulation has long been a subject of interest to physiologists. ~'3 In canine models, an ablated, akinetic right ventricle functions essentially as a conduit; the left ventricle alone maintains normal hemodynamics at rest. ~ The Fontan operation, based upon a model proposed in 19554 and first applied in 1968, 5 permits study of a human circulation in which right atrial flow is channeled directly into the pulmonary artery (atriopulmonary anastomosis in single ventricle or tricus-

From the Divisions of Cardiology, Departments of Medicine and Pediat- rics, the Division of Cardiothoracic Surgery, Department of Surgery, and the Adult Congenital Heart Disease Program, UCLA Medical Center.

Received for publication Oct. 5, 1987; accepted Nov. 13, 1987.

Reprint requests: Joseph K. Perloff, M.D., UCLA School of Medicine, Division of Cardiology, Room 47-123 CHS, Los Angeles, CA 90024-1679.

pid atresia). Despite these and other fundamental differences from the normal circulation, clinical results of the Fontan operation remain good even in the relatively long term (7 to 16 years)2 Exercise performance improves, but not surprisingly, remains subnormalJ -10

Atrial pacing, introduced by Sowton et al. in 1967,1~ has been used to study the physiologic response of the circulation to isolated, controlled increments in heart rate. 1~ In contrast to dynamic exercise, pacing-induced tachycardia in the intact circulation is accompanied by a fall in stroke volume and by little or no change in cardiac output. ~2 However, the response to an increase in heart rate as an isolated variable has not been e ~ in hearts devoid of a subpulmonic right ventricle, i.e., a circulation characterized by direct atriopulmonary

837

April 1988 838 Barber et al. American Heart Journal

Table I. Hemodynamic responses to exercise and pacing

Rest Exercise Probability Rest Pacing Probability

89 + 18 113 _+ 20 p < 0.001 91 _+ 15 153 _+ 16 p __< 0.001 Heart rate (bpm) Systemic blood pressure

(ram Hg) Systolic 119 _+ 14 136 _+ 25 Diastolic 77 _+ 12 87 -+ 14

Mean pulmonary artery 14 ± 2 20 + 4 pressure (ram Hg)

Pulmonary artery oxygen 68 _+ 6 31 + 8 saturation ( % )

Cardiac index 2.6 _+ 0.3 4.6 ± 1.0 (L/min/m 2)

Pulmonary vascular 5.2 + 1.0 4.5 ± 1.1 resistance (U/m 2)

Stroke volume (ml/heart 30 _+ 7 36 ± 11 beat)

Systemic vascular 34 ± 7 20 + 3 resistance (U/m 2)

NS 104 _+ 15 105 _+ 18 NS NS 71 _+ 13 73 _+ 17 NS

p_< 0.005 12 ± 3 16 _+ 3 p ~< 0.05

p ~ 0.001 72 _+ 7 64 _+ 5 p ~< 0.05

p _< 0.001 2.5 _+ 0.5 2.2 _+ 0.7 NS

NS 4.6 _+ 1.5 7.8 _+ 1.8 p __< 0.005

NS 29 _+ 8 15 + 5 p ~ 0.005

p ~ 0.005 32 _+ 10 31 _+ 5 NS

Table I I . Exercise arteriovenous oxygen extract ion in four adul ts

Rest Exercise

Heart rate (bpm) 79 + 6 137 + 22 VO2 (ml/min/m 2) 147 _+ 4 709 _+ 162 CI (L/min/m 2) 2.9 + 0.8 5.0 _+ 1.5 A-VO2 difference (m/OiL) 55 + 13 141 _ 30 PAO2 sat (%) 70 _+ 6 25 _+ 5 PVR (U) 1.3 0.9 SVR 19 10.8

VO2 = oxygen consumption; CI = cardiac index; A-V02 = arteriovenous oxygen; PAO2 sat ffi pulmonary arterial oxygen saturation; PVR = pulmonary vascular resistance; SVR = systemic vascular resistance.

flow. T h e F o n t a n o p e r a t i o n is a m o d e l for a d d r e s s i n g t h i s q u e s t i o n . A c c o r d i n g l y , we c o m p a r e d t h e r e s p o n s e p r o v o k e d b y i s o l a t e d i n c r e m e n t s in h e a r t r a t e ( a t r i a l p a c i n g ) t o t h e r a t e e q u i v a l e n t exe rc i s e r e s p o n s e in p a t i e n t s in w h o m a s u b p u l m o n i c r i g h t v e n t r i c l e h a d b e e n e x c l u d e d f r o m t h e c i r c u l a t i o n b y a F o n t a n a n a s t o m o s i s ( a t r i a l - d e p e n d e n t p u l m o n a r y c i r c u l a t i o n ) .

METHODS

Nine pat ients , four females and five males, underwent Fon tan procedures at the Universi ty of California Los Angeles Medical Center. Seven had double- inle t left ventricles (single ventricle) and two had t r icuspid atresia. All pa t ients had a t r iopulmonary anastomoses by the same surgeon (H.L.), and each pa t ien t met the preoperat ive selection cri teria of Choussat et al.18 Ages ranged from 6 years to 35 years (mean age 17 years); five pat ients were over 18 years of age. All except one were in stable sinus rhy thm and remained so throughout the s tudy period.

The exception was a pa t ien t with t r icuspid atresia, inter- mi t t en t high-degree hear t block, and an epicardial atrio- ventr icular pacemaker set a t 80 bpm. She overdrove the pacemaker during exercise. For the pacing protocol, her own pacemaker rate was incremental ly increased.

Informed consent was secured, and cardiac catheteriza- t ion was performed a mean of 1.4 years (-+0.6 years s tandard deviation) after surgery. Pediatr ic pat ients were brought to the laboratory the evening before s tudy to familiarize them with the equipment. Catheterizat ion employed s tandard techniques. After percutaneous venipuncture, a bal loon- t ipped flow-directed thermodi lut ion catheter was advanced into the pulmonary artery. Resting hear t rate, ar ter ial blood pressure, r ight atr ial pressure and oxygen saturat ion, pulmonary arter ial pressure and oxygen saturat ion and, when feasible, pulmonary capil lary wedge pressure were recorded. Thermodi lut ion cardiac outputs , 14 were obtained with the use of iced 5 % dextrose aliquots and an Elecath cardiac ou tput computer (Electro- Catheter Corp., Rahway, N.J.). Five of the pat ients (each over 18 years of age) also had cardiac outputs de termined by the Fick priniciple and by the Douglas bag method. TM

Oxygen consumption was measured with a Tissot spirom- eter and a Beckman oxygen analyzer (Beckman Instru- ments Inc., Brea, Calif.). Blood oxygen saturat ions were assessed by reflectance oximetry with an American Opti- cal oximeter (Reichert Scientific Instruments , Buffalo, N.Y.) s tandardized by the method of Van Slyke and Neill. is Pressures were recorded via fluid-filled catheters a t tached to S ta tham strain gauges (Gould Inc. Cardiovas- cular Products , Oxnard, Calif.) using an Electronics for Medicine VR-12 mult ichannel recorder (Electronics for Medicine/Honeywell Inc., Pleasantvil le, N.Y.).

After resting measurements were recorded, supine bicycle exercise was performed with a S ta tham catheterizat ion table cycle ergometer (Gould Inc.). Exercise level was tai lored to each pa t ien t in an a t t empt to achieve a

Vo lume 115 Number 4 Cardiac function post Fontan procedure 839

EXERCISE FACTOR

12, .... /~ -

I o rest .,, x I0t" • restonly t / / . ~

~ / •exercise . / , ,

z_~ 8~ ,." / / / / / I . " / . "

~.~ I f j 4 /

2 I I 0 200 400 600 800 I000 1200

OXYGEN CONSUMPTION INDEX (ml 0 2 / m i n / m 2 )

Fig. 1. Comparison of cardiac index and oxygen consumption at rest and exercise to generate an "exercise factor." The solid line and dashed lines are the normal mean and 95% confidence limits."

duration of at least 6 minutes. With a constant pedal rate, exercise proceeded until leg fatigue or shortness of breath was sufficiently marked so that the patient could not be encouraged to continue. During the final minute of each workload, we determined the heart rate, systemic blood pressure, pulmonary arterial and right atrial pressures and oxygen saturations, and cardiac output by thermodilution. At the end of the final phase of exercise, all measurements were repeated (Fick cardiac outputs were additionally performed in four patients).

When all parameters returned to baseline, an NHLBI bipolar pacing catheter was passed into the right atrium via a separate venipuncture. Baseline measurements of heart rate, systemic arterial pressure and oxygen saturation, p,,lmonary arterial and right atrial pressures and oxygen saturations (pulmonary capillary wedge pressure when feasible) were recorded and thermodilution cardiac outputs were measured. Atrial pacing was begun with 2 to 5 mA. The current was increased and the catheter tip was repositioned until consistent atrial pacing was achieved. The rate was set at 10 bpm faster than the baseline heart rate and was increased in 10 bpm increments. The pacing rate was increased every 3 minutes until atrioventricular block occurred or until a heart rate was achieved equal to that at peak exercise or double the baseline heart rate. Hemodynamic measurements were repeated after 2 minutes at each rate increment and again at the termina- tion of atrial pacing.

Total pulmonary resistance was calculated by dividing mean pulmonary artery pressure by cardiac output. Pul- monary vascular resistance was calculated by dividing the difference of mean pulmonary artery pressure and capillary wedge pressure (when available) by cardiac output.

i '"

4

o °

J ~ e-

i f I I I i I 2 3 4 5

F I C K C A R D I A C INDEX ( L / m i n / m 2 )

Fig. 2. Comparison of cardiac index (exercise and atrial pacing) by thermodilution and Fick techniques. The open circle is the one patient with anatomic connections that precluded a satisfactory thermodilution assessment of upper and lower body venous return.

Systemic vascular resistance was determined by dividing the difference of mean systemic arterial and right atrial pressures by cardiac output. Stroke volume was determined by dividing the cardiac output by the heart rate. Each result was corrected for body surface area by means of the nomogram of Dubois. 16 In those patients in whom oxygen consumption and Fick cardiac outputs were measured, the "exercise factor" was calculated as the ratio of the increment in cardiac index to the increment in oxygen consumption rate index from baseline to peak exerciseJ 7 Results were compared to published values for the responses of normal and near normal children and adults to dynamic exercise ls-22 and atrial pacing. ~3 After the control observations, exercise and pacing measurements were recorded, and each patient had a right atrial anglo- gram in the anteroposterior and lateral projections to assess the anastomotic pathway.

Stat i s t ica l a n a l y s e s . Exercise and atrial pacing hemodynamic measurements were compared to their respective baseline resting parameters by means of a paired Stu- dent's t test. The correlation between thermodilution and Fick cardiac outputs was assessed by linear regression (least squares). A probability (p) value of less than 0.05 was considered to indicate statistical significance. All data are expressed as mean + standard deviation (S.D.).

RESULTS

Resting hemodynamics (Table I). Heart rate, systemic blood pressure , and m e a n p u l m o n a r y ar ter ia l pressure were normal . R igh t a t r ia l m e a n pressure averaged 15 m m Hg and ranged f rom 0 to 3 m m Hg higher t h a n the p u l m o n a r y a r t e ry pressure (mean

April 1988

840 Barber et al. American Heart Journal

difference 1 mm Hg). One patient with a 3 mm Hg resting difference had, by right atrial angiogram, an obstructed anastomosis (10 mm at the site of attach- ment to the pulmonary artery, original surgical size = 20 mm). Average resting p|]imonary arterial oxygen saturation and systemic arterial oxygen saturation were in the lower range of normal.

Exercise and atrial pacing (Table I). The increments in heart rate during exercise and atrial pacing were equivalent, and all exercising patients remained in sinus rhythm. With exercise, there was a 14% increase in systemic arterial pressure and the expected decrease in systemic vascular resistance (Tables I and II), but with atrial pacing, there were no significant changes. Mean pulmonary artery pressure increased 43 % with exercise and 33 % with pacing. With exercise (excluding the one patient with 50% anastomotic narrowing), right atrial pressure rose from 13 _+ 4 to 27 + 1 mm Hg; the corresponding pulmonary arterial pressures were 14 _+ 2 and 20 + 4 mm Hg. The calculated pulmonary vascular resistance showed a slight but statistically insignificant decrease. Pulmonary oxygen saturation fell more with exercise than with atrial pacing (54 % vs 11% ); the corresponding cardiac index rose 77 % with exercise but fell 12 % with atrial pacing. Calcu- lated stroke volume rose insignificantly with exercise but fell significantly with atrial pacing.

Exercise oxygen kinetics. In five patients 26 Jr 6 years of age (three men, two women), Fick cardiac outputs were measured at rest; in four, measurements were also achieved during exercise (Table II). Heart rate rose to 75 % of predicted normal. Mean oxygen consumption and mean cardiac index at rest were normal. Resting arteriovenous oxygen difference was slightly increased at 55 + 13 ml O/L (normal = 40 ml O/L). 14 Total exercise time average 13.5 minutes (range 6 to 25 minutes) at a workload of 42 W (25 to 63 W).

The cardiac index-oxygen consumption index relationship was low normal at rest and fell below the lower limits of normal with exercise (Fig. 1). The "exercise factor" was subnormal at 3.2 _+ 2.3 (normal _~ 6) 19 due to a blunted increase in cardiac output.

Fick versus thermodilution cardiac outputs. Seven simultaneous cardiac outputs by thermodilution, and by the Fick principle were determined in five patients; correlation coefficient was r = 0.35 (Fig. 2). However, in one patient with single ventricle, bilat- eral superior vena caval connections and levocardia in situs inversus, the surgical procedure included a Glenn anastomosis of the left superior cava to the left pulmonary artery, ligation of the right superior

vena cava (anomalous in situs inversus), and a direct Fontan anastomosis from right atrium to pulmonary artery. In this case, there was no site for injection of a thermal indicator that could accurately assess total body cardiac output. If that data point (Fig. 2) were excluded, the correlation coefficient for thermodilution vs Fick cardiac output improves to r = 0.77. Regarding our thermodilution technique for evaluating cardiac output, patients served as their own controls. Changes from baseline with each intervention (exercise, pacing) were therefore believed to be representative. In addition, resting and exercise thermodilution cardiac outputs were similar to the resting and exercise Fick data in Fontan patients reported by Ben Shachar et al. 1°

DISCUSSION

The Fontan repair with an atriopulmonary anastomosis is a human model for studying an atrial- dependent circulation devoid of a subpulmonic right ventricle. The model is superior to experimental ablation of the right ventricular free wall 1 or to Uhl's anomaly (parchment right ventricle), because in both of these examples the interventricular septum remains dynamic, and paradoxic septal motion may contribute materially to pulsatile flow into the pulmonary artery. 3, 25

Heart rate has not previously been studied as an isolated variable in patients devoid of a subpuhnonic right ventricle with atrial-dependent pulmonary cir- culations. Low pulsatile pulmonary flow at low perfusion pressures and abnormal contraction patterns of the subaortic left ventricle after Fontan anastomoses differ substantially from a circulation with two concordant subarterial ventricles in which the hemodynamic response to atrial pacing has been established.S, 9.10, 26

We and others ~-28 have shown by Doppler interro- gation that flow into the pulmonary artery after the Fontan operation is biphasic. There is active flow in response to right atrial contraction, followed by a passive flow phase, but it is unclear which phase contributes more to forward flow. ~

Stable sinus taehycardia during exercise in our patients permitted comparison with rate-equivalent tachycardia induced by atrial pacing. Right atrial pacing resulted in an increase in pulmonary arterial pressure and a decrease in stroke volume, but no significant change in cardiac output (Table I). Sys- temic and pulmonary vascular resistances did not fall. The increase in pulmonary arterial pressure implies that augmented venous return occurred without a decline in pulmonary vascular resistance and despite no significant change in cardiac output

Volume 115 . . . b . , 4 Cardiac function post Fontan procedure 841

(Table I). The absence of an increment in cardiac output was due to the decrease in stroke volume at accelerated paced rates, as described in normal subjects. 23

The physiologic response to atrial pacing after a Fontan atriopulmonary anastomosis was similar to the response in normal hearts, indicating the dispensability of the right ventricle when heart rate is examined as an isolated variable. Conversely, the hemodynamic response to isotonic exercise in an atrial-dependent pulmonary circulation is funda- mentally different from normal, s-l° underscoring the role of a subpulmonic right ventricle in preserving the exercise response. The disparity in responses between atrial pacing and dynamic exercise in our patients was similar in direction but quantitatively blunted when compared to subjects with two corcor- dant subarterial ventricles.

The authors wish to thank Dr. Ralph Weiss for allowing us to study the patient under his care.

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hemodynamic responses to isolated increments in heart rate by atrial pacing after a fontan procedure

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