Delayed Improvement in Exercise Capacity With Restoration of Sinoatrial Node Response in Patients After Combined Treatment With Surgical Repair for Organic Heart Disease and the Maze Procedure for Atrial Fibrillation

Subjects

Twenty-five patients who received cardiac surgery with the Maze procedure were enrolled in this study. Informed consent was obtained from each patient. The clinical characteristics of each patient are listed in Table 1⇓. Patients comprised 15 men and 10 women, and their ages were 37 to 70 years (mean, 57±8 years). Atrial fibrillation was permanent in 23 patients and paroxysmal in 2. Duration of atrial fibrillation was 0.7 to 20 years (mean, 7±7 years). In 2 patients with paroxysmal atrial fibrillation, 1 (No. 12) suffered from rapid ventricular response during the attack once a week despite the medical treatments and another (No. 16) repeated hospitalization for the treatment of exaggerated congestive heart failure induced by paroxysmal atrial fibrillation. Organic heart diseases were valvular heart disease in 18 patients and atrial septal defect in 7. In patients with atrial septal defect, 3 had mitral valve regurgitation and 4 had tricuspid valve regurgitation. These patients also received valve repair. There were 6 reoperated cases in patients with mitral valve disease. The initial procedures were mitral valve replacement in 3, mitral valve plasty in 2, and open mitral commissurotomy in 1. The interval between the two operations was 2 to 15 years.

Maze Procedure

In April 1992, the surgical department of our institution started to apply the Maze procedure in cardiac surgery of the patients with organic heart disease and atrial fibrillation. Initially, the application of the combined surgery was limited in selected patients. Since September 1992, the combined surgery was performed when possible in the cardiac surgery of consecutive patients with valvular or congenital heart disease and atrial fibrillation. However, patients who required emergency surgery and those with severe heart failure were omitted because of the need to shorten cardiopulmonary bypass time.⁸

The operative procedure was fundamentally the same as that initially described by Cox and associates.⁴ However, several modifications were made in the patients used in the present study.¹⁰ In brief, a longitudinal incision of right atrial free wall was performed from the right atrial appendage (instead of the superior vena cava) down to the inferior vena cava because Cox’s original incision transverses the sinus node arteries and deteriorates the postoperative sinus node function.¹¹ In addition, other incisions that transverse sinus node arteries were substituted by cryosurgical procedure to avoid an interruption of sinus node arteries. Patients 5 through 25 received this modification. Second, in patients who required surgical treatments for the mitral valve, division of the superior vena cava was performed to improve the exposure of the mitral valve to shorten the operative time. This modification was also performed by Dr Cox in his first modification of the Maze procedure.¹²

Cardiopulmonary Exercise Testing

Exercise capacity of each patient was examined by a symptom-limited exercise test. The exercise test was performed on an upright bicycle ergometer (Combi 232C). Exercise workload was increased by a ramp incremental protocol of 15 W/min after 1-minute warm-up at 0 W. Exercise was continued until the patient complained of symptomatic limits on dyspnea or leg fatigue, that is, 19 to 20 on the Borg scale.¹³ During the exercise test, heart rate was continuously monitored, and blood pressure was measured every minute. Expired gas of the patient was measured on a breath-by-breath basis during the test using a respiromonitor AE280 (Minato Medical Science) connected to a personal computer with analyzing software.

Respiratory gas was analyzed as a value of averaged data every 15 seconds. Peak oxygen uptake was defined as a value of averaged data in the final 15 seconds of the exercise.

All patients performed the symptom-limited exercise test 1 week before the surgery and 1 month and 6 months after the surgery. The initial 10 patients performed an additional exercise test 1 year after the surgery.

Statistical Analysis

Data are presented as mean±SD. Variables obtained at rest, at an equivalent workload, and at peak exercise were compared using repeated-measures ANOVA and Scheffe’s F test. Linear regression analysis was used to evaluate the relation between the two variables. A P value of less than .05 was considered significant.

Cardiopulmonary Bypass Time and Cardiac Arrest Time of Combined Surgery

Cardiopulmonary bypass time of the patients ranged from 119 to 291 minutes (mean, 210±47 minutes). Cardiac arrest time during surgery ranged from 75 to 217 minutes (mean, 137±32 minutes).

Effects of Combined Surgery on Left Atrial and Ventricular Chamber Dimension and Function

Echo-Doppler examination indicated significant decrease in left atrial dimension after surgery (P<.01). Atrial wave in transmitral flow profile was observed in 14 of 25 patients (Table 2⇓). Although mean values of left ventricular dimension and fractional shortening did not change after the surgery, effects of surgery on these variables were equivocal because of the differences in preoperative conditions of each patient.

Postoperative Cardiac Rhythm and Drug Administration

Sinus rhythm was obtained in 23 of 25 patients (92%) 1 month after the surgery. In the remaining 2 patients, 1 patient showed junctional rhythm and later changed to sinus rhythm and 1 patient continued atrial fibrillation for 6 months. Thus, 6 months after the surgery, atrial fibrillation associated with heart diseases was converted to sinus rhythm in 24 of 25 patients (96%) examined.

Digitalis was administered in 23 patients before the surgery and was continued in patients who still had clinical symptoms of congestive heart failure after surgery. Therefore, digitalis was continued in 11 of 23 patients with sinus rhythm 1 month after the surgery and in 10 of 24 patients with sinus rhythm 6 months after the surgery. A class Ia antiarrhythmic drug was also administered in 17 patients 1 month after the surgery and in 11 patients 6 months after the surgery because they had frequent atrial arrhythmia after surgery.

Cardiopulmonary Response to Exercise

Fig 1⇓ shows the representative ECGs at rest and at peak exercise. Fig 2⇓ shows the representative trend graphs of heart rate and oxygen uptake during the exercise tests. Although sinus conversion was obtained 1 month after the surgery, heart rate response was markedly attenuated (minimal increase during exercise and delayed decrease during the recovery period). However, 6 months after the surgery, heart rate response was almost normalized; there was a small increase in heart rate at the onset of exercise, high heart rate at peak exercise, and a rapid decrease in heart rate immediately after cessation of exercise. On the other hand, an increase in oxygen uptake during exercise was almost equivalent in the repeated exercise tests, and peak oxygen uptake apparently increased 6 months after the surgery.

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Figure 1.

Representative ECG at rest and peak exercise before, 1 month after, and 6 months after combined surgery with the Maze procedure.

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Figure 2.

Representative trend graphs of heart rate (left) and oxygen uptake (right) during exercise before (——), 1 month after (—•—), and 6 months after (—○—) combined surgery with the Maze procedure. Arrows indicate peak exercise.

The mean values of heart rate and oxygen uptake in 23 patients with sinus rhythm 1 month after the surgery are summarized in Fig 3⇓. Heart rate at the resting condition did not change. Peak heart rate was 172±23.2/min before surgery due to a rapid ventricular response of atrial fibrillation. Although sinus rhythm was obtained 1 month after the surgery, peak heart rate was only 107±16.7/min (P<.01 versus before surgery). However, it increased to 130±20.2/min 6 months after the surgery (P<.01 versus before and 1 month after surgery).

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Figure 3.

Graphs showing the serial changes in heart rate (left) and oxygen uptake (right) during exercise in 23 patients before (——), 1 month after (—•—), and 6 months after (—○—) combined surgery with the Maze procedure. **P<.01 vs before surgery; ##P<.01 vs 1 month after surgery.

Duration of preoperative atrial fibrillation was correlated with neither heart rate response 1 month after surgery (r=.12) nor increase in peak heart rate from 1 to 6 months after surgery (r=.14). There were 4 patients with atrial septal defect who did not receive the division of the superior vena cava. The peak heart rate of these patients was 110±16.9/min 1 month after the surgery and 129±11.4/min 6 months after the surgery, which was not different from the patients with the division of superior vena cava (1 month after surgery, 106±17.0/min; 6 months after surgery, 130±21.8/min). Digitalis was administered in 11 patients after the surgery; however, no statistical differences were observed in resting heart rate or its response to exercise between the patients with and without digitalis administration (Table 3⇓).

Peak oxygen uptake did not increase 1 month after surgery (950±300 mL/min, 17.6±4.5 mL · min⁻¹ · kg⁻¹) as compared with that before surgery (940±310 mL/min, 17.5±4.2 mL · min⁻¹ · kg⁻¹). However, concomitant with increases in heart rate during the exercise, peak oxygen uptake significantly improved 6 months after surgery (1160±350 mL/min, 20.7±4.0 mL · min⁻¹ · kg⁻¹, P<.01, versus 1 month after surgery). Moreover, the extent of increases in peak oxygen uptake and peak heart rate from 1 month to 6 months after surgery were closely correlated (r=.79, P<.01, Fig 4⇓). However, peak oxygen uptake was not different between patients with and without atrial wave in transmitral flow.

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Figure 4.

Graph showing relation between increase in peak oxygen uptake and increase in peak heart rate from 1 month to 6 months after combined surgery with the Maze procedure.

Peak oxygen pulse (peak oxygen uptake divided by peak heart rate) significantly increased 1 month after surgery as compared with that before surgery (5.5±1.5 to 8.5±2.4 mL, P<.01), but it did not show further changes 6 months after surgery (8.9<27.2.2 mL). On the other hand, a slope of the relation between oxygen uptake and workload (|gDoxyg>±2.2 mL). On the other hand, a slope of the relation between oxygen uptake and workload (Δoxygen uptake/Δwork ratio) increased from 1 to 6 months after surgery (Fig 5⇓).

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Figure 5.

Bar graphs showing changes in peak oxygen pulse (left) and Δoxygen uptake/Δwork (ΔVO₂/ΔW) ratio (right) before, 1 month after, and 6 months after combined surgery with the Maze procedure.

Systolic blood pressure became higher 6 months after surgery compared with conditions before and 1 month after surgery, whereas ventilatory response did not show any changes in the repeated exercise tests (Fig 6⇓).

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Figure 6.

Bar graphs showing changes in systolic blood pressure (BP) (left), ventilatory equivalent of carbon dioxide production (VE/VCO₂) (center), and minute ventilation (VE) (right) before (⊤▩), 1 month after (⊤▪), and 6 months after (⊤□) combined surgery with the Maze procedure. **P<.01 vs before surgery; ##P<.01 vs 1 month after surgery. Ex indicates exercise.

Symptom-limited exercise testing was again performed 1 year after the surgery in 10 patients. However, there were no further changes in rest heart rate, peak heart rate, or peak oxygen uptake from 6 months to 1 year after surgery (Table 4⇓).

There was one unsuccessful case who showed atrial fibrillation even 6 months after surgery. Although the same dose of digitalis was administered in this patient, both an increase in ventricular rate during mild to moderate extent of exercise and its decrease during the recovery period remained attenuated after surgery (Fig 7⇓).

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Figure 7.

Representative trend graph of heart rate during exercise in a patient with mitral regurgitation and atrial fibrillation before (——), 1 month after (—•—), and 6 months after (—○—) mitral valve plasty and the Maze procedure. In this case, atrial fibrillation was continued despite combined surgery. Arrows indicate peak exercise.

Application of the Maze Procedure to the Surgery of Patients With Heart Disease and Atrial Fibrillation

Initial candidates of the Maze procedure were patients with lone atrial fibrillation.³ Although atrial fibrillation is the most common arrhythmia in the subjects without heart disease,¹⁴ it is also a common complication of patients with heart disease. Previous reports indicate that the Maze procedure restored sinus rhythm even in patients with heart disease.^{6 7 8 9} Thus, the Maze procedure will be of much more value if it can be applied to cardiac surgery for patients with heart disease.

The results of the present study and a previous report⁸ showed that addition of the Maze procedure required a longer bypass run and cardiac arrest, which might cause postoperative morbidity. However, we also examined the risk and benefit of combined Maze procedure in the surgery of patients with valvular heart diseases and concluded that the restoration of sinus rhythm by an addition of the Maze procedure was worthwhile despite the longer operative time, larger blood loss, and longer postoperative respiratory care.¹⁵

The present study showed an increase in peak oxygen uptake of the patients after combined surgery with the Maze procedure. Because an improvement of exercise capacity is one of the major clinical purposes of the surgery for patients with heart diseases, we believe that the results of the present study enhance the clinical value of the Maze procedure in cardiac surgery.

Attenuated Sinoatrial Node Response to Exercise After the Maze Procedure

The attenuated heart rate response 1 month after surgery was characterized as follows: no increase in heart rate at the onset of exercise, low heart rate at peak exercise, and no decrease in heart rate immediately after cessation of exercise (Fig 2⇑). This heart rate response can be mimicked in the experimentally denervated heart¹⁶ and transplanted heart.¹⁷ Thus, the attenuated heart rate response to exercise early after the Maze procedure is seemingly caused by the denervation of the sinoatrial node due to multiple incisions in atrial wall.

The present study also demonstrates the recovery of heart rate response 6 months after surgery. If the attenuated heart rate response early after the Maze procedure is caused by denervation of the sinoatrial node, its recovery late after surgery is also consistent with the time course of reinnervation of the sinoatrial note; reinnervation of the parasympathetic nerve was observed as early as 26 days and that in the sympathetic nerve was as early as 74 days after experimentally denervated heart.¹⁸ Moreover, we examined the sinoatrial node response of the patients with mitral stenosis and atrial fibrillation who received balloon mitral commissurotomy and thereafter converted to sinus rhythm by the electrical cardioversion.¹⁹ Although this combined therapy was almost the same as the combined surgery except for the surgical procedures, heart rate reached 146±14/min at peak exercise 5 days after sinus conversion, and further augmentation of peak heart rate was not observed in the late phase after electrical cardioversion. Thus, these lines of evidence lead to the hypothesis that the attenuated sinoatrial node response to exercise early after combined surgery may be caused by the denervation of the sinoatrial node due to the Maze procedure, and its recovery late after surgery represents the time course of reinnervation of the sinoatrial node.

Heart Rate Response and Exercise Capacity

An increase in heart rate plays an important role in raising cardiac output during exercise, which is demonstrated by the direct linear relation between heart rate and cardiac output during exercise.²⁰ Thus, the attenuated sinoatrial node response early after the Maze procedure undoubtedly deteriorates the exercise capacity of the patient. However, the peak oxygen uptake was preserved (Fig 3⇑) as compared with that before surgery by increasing peak oxygen pulse (Fig 5⇑). Oxygen pulse is the product of stroke volume and arteriovenous oxygen difference. The previous report indicated that the augmentation of these two factors was observed during exercise in patients with poor heart rate response due to heart transplantation.²¹ Moreover, an increase in stroke volume could be accomplished by the surgical repair of heart disease in patients we examined. Thus, both factors play major roles in preserving exercise capacity of the patient despite the attenuated heart rate response early after combined surgery.

An improvement of sinoatrial node response in the late phase after the surgery increased both the peak oxygen uptake (Fig 3⇑) and Δoxygen uptake/Δwork ratio (Fig 5⇑), which indicates the amelioration of impaired oxygen uptake.²² However, the extent of the improvement in exercise capacity was not uniform and depended on the recovery of heart rate response (Fig 4⇑). We could not find any relation between the extent of recovery in heart rate response and preoperative characteristics or surgical procedures of each patient. Whatever the cause of this difference, the present results indicate that the more the heart rate response recovers, the more the exercise capacity improves. Because the changes in heart rate response after surgery appear to depend on the extent and rate of denervation and reinnervation of the sinoatrial node, maneuvers to avoid denervation and/or to enhance reinnervation may have advantageous effects on the exercise capacity of the patient after surgery.

Limitations of the Study

First, administration of drugs was not discontinued when patients performed the exercise test because it was uncertain whether atrial fibrillation might occur even if the drugs were discontinued. However, there were no statistical differences in heart rate response between patients with and without digitalis (Table 3⇑). Second, the modifications of the operative procedure were performed in the series of patients we examined. Application of cryosurgical procedure may influence the results of the present study. Moreover, comparison of the data between the patients with and those without division of the superior vena cava is not conclusive because of the small number of patients in the latter group.

Conclusions

The combined treatment of surgical repair for heart disease and the Maze procedure for atrial fibrillation improved the exercise capacity of the patients. This combined surgery was of value for the patients with heart disease and atrial fibrillation; however, the extent of improvement in exercise capacity after the surgery largely depended on late recovery of the sinus node response to exercise.