Atenolol therapy for exercise-induced hypertension after aortic coarctation repair

CONGENITAL

HEART DISEASE

Atenolol Therapy for Exercise-Induced Hypertension After Aortic Coarctation Repair Rae-Ellen W. Kavey, MD, John L. Cotton, DAD,and Marie S. Blackman, MD

After successful repair of coarctation of the aorta in childhood, exercise-induced upper body systolic hypertension is well documented. Beta blockade has been shown to reduce the arm/leg gradient in untreated coarctation of the aorta; treatment before coarctation repair has decreased paradoxical hypertension after repair. Ten patients with successful surgical repair of coarctation, defined as a resting arm/leg gradient of I18 mm Hg, were evaluated by treadmill exercise before and after fi blockade with atenolol. Mean age was 5.5 years at repair and 18 at study. At baseline evaluation, systolic blood pressures at termination of exercise ranged from 201 to 270 mm Hg (mean 229 mm Hg). Arm/leg gradients at exercise termination ranged from 30 to 143 mm Hg (mean 64). Followup treadmill exercise studies were performed after fi blockade. Upper extremity systolic pressures at exercise termination were normalized in 9 of 10 patients. Maximal systolic blood pressure recorded at exercise termination ranged from 163 to 223 mm Hg (mean 196 mm Hg, p 50.005). Arm/leg gradient at termination of exercise also decreased significantly to a mean of 51 mm Hg (p 50.05). No patient had symptoms on atenolol and exercise endurance times were unchanged. The study results in this small series suggest that cardioselective B blockade can be used to treat exercise-induced upper body hypertension effectively after surgical repair of coarctation. Because a high incidence of premature cardiovascular disease has been well documented after satisfactory surgical repair, the findings are of importance for this group Qf postoperative patients. (Am J Cardiol 1990;66:1233-X236)

From the Division of Pediatric Cardiology, State University of New York Health Science Center at Syracuse, Syracuse, New York. Manuscript received January 1, 1990; revised manuscript received and accepted July 9, 1990. Address for reprints: Rae-Ellen W. Kavey, MD, Division of Pediatric Cardiology, SUNY Health Science Center at Syracuse, 725 Irving Avenue, Room 804, Syracuse, New York 13210.

n exaggeratedupper body hypertensive response to exerciseafter repair of coarctation of the aorta has been well described.lesSuch hypertension theoretically leaves patients at an accelerated risk for acquired cardiovascular diseasedespite satisfactory surgical repair with elimination of resting upper extremity hypertension and arm/leg pressure gradients. Longterm follow-up studies have documented significant cardiovascular morbidity and premature mortality in patients who have undergone satisfactory surgical repair of coarctation.6-9Persistent systolic hypertension in the context of increased cardiac output, such as with exercise, would be anticipated to contribute to this. Pharmacologic treatment with /3 blockade has been shown to reduce upper limb hypertension and arm/leg gradient before coarctation repair.iO Treatment with 0 blockade before coarctation repair has resulted in a significant decrease in acute paradoxical hypertension postoperatively.” This study was undertaken to evaluate the effect ‘of cardioselective /3 blockade on exercise-induced upper extremity hypertension and arm/leg gradient after coarctation repair.

A

METHODS

The records of the Division of Pediatric Cardiology were reviewed for patients >lO years of age who had undergone previous repair of isolated coarctation of the aorta. To exclude residual coarctation of the aorta as the cause of hypertension, only patients with resting arm/leg systolic blood pressuredifference I1 8 mm Hg were considered for inclusion. Those who had undergone previous treadmill testing with exercise-induced upper extremity systolic blood pressure ,220 mm Hg, or arm/leg gradient 230 mm Hg, or both, were contacted, of these, 13 agreed to undergo evaluation. Treadmill exercise: Initial blood pressure measurements were taken in the supine position. Right arm blood pressurewas determined with an oscillometric device (Dinamapp Model 1846SX) using a cuff of appropriate size. Blood pressurestaken in this way have been shown to correlate well with direct central aortic and radial artery pressures.12J3Right leg systolic blood pressure was determined using a standard leg cuff on the thigh with a Doppler probe over the popliteal artery. Heart rate and rhythm were monitored continuously using leads Vi, V5 and aVF. Patients were exercised using the modified Bruce protocol. Right arm and leg blood pressureswere recorded immediately after termination of exercise, as were heart rate and electrocardiogram. These determinations were repeated every 2 minutes throughout the IO-minute recovery period.

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TABLE

Pts.

1 2 3 4 5 6 7 8 9 10

I Characteristics

of Study Group

Age at Repair (yr) 9 7 17 14 l/12 l/12 12 7 9 7/12

A/L Grad = systolic blood pressure difference anastomosis; SFA = sub&&n flap angioplasty.

Years of Follow-Up 11 9 1 3 19 20 5 4 11 19 in mm Hg between

Surgical Technique

R/E WE PA SFA R/E R/E R/E PA R/E R/E right arm and either

Baseline BP A/L Grad

Exercise BP A/L Grad

Atenolol BP A/L Grad

126/76,14 120/70,3 132/70,0 136/60,18 118/50,0 144/80,9 140/78,15 126/82,0 147/77,0 126/62,0

249/69,109 260/80,122 210/80,30 270/65,69 220/60,91 220/70,143 240/60,73 201/68,63 216/84,74 207/67,65

209/63,79

leg; BP = blood pressure;

PA = patch angioplasty;

185/70,28 191/61.39 214/72.18 163/65,51 203/76,60 196/61,66 165/57,30 203/60,33 223/68,109 R/E = resection

and end-to-end

statistical significance, systolic blood pressuresdid fall into the normal range in 7 of 10 patients. Arm/leg gradients persisted at rest with atenolol in 7 patients, ranging from 7 to 19 mm Hg. With atenolol, peak exercise heart rates were significantly reduced to a mean of 154 per minute (p CO.005). Upper extremity systolic blood pressuresat exercisetermination normalized in 9 of 10 patients, as shown in Figure 1. The maximal systolic blood pressure recorded at peak exercise ranged from 163 to 223 mm Hg (mean 196), a significant decrease compared with baseline reading (p SO.005). Exercise arm/leg gradients also significantly decreased to a mean of 51 mm Hg (p 50.05). In 1 patient, effective /3 blockade did not decreasesystolic hypertensionwith exRESULTS Study results are listed in Table I. On pretesting ercise and treatment was discontinued. No patient had evaluation (before exercise testing), systolic blood pres- symptoms related to atenolol therapy. Endurance times sures ranged from 106 to 140 mm Hg (mean 128). after ,L3blockade did not differ significantly from times While all pressureswere within the normal range, the before treatment (Figure 2). systolic blood pressure was above the 80th percentile in 8 of 10 patients when compared with age- and gender- DISCUSSION In this group of patients, studied after satisfactory specific normal subjects.I4 Diastolic blood pressures were normal in all subjects. Resting arm/leg gradients surgical repair of coarctation of the aorta, severeexerwere only present in 5 patients and ranged from 3 to 18 cise-induced upper extremity systolic hypertension was effectively treated by cardioselective/? blockade. Blood mm Hg (mean 7). At baseline treadmill evaluation, resting systolic pressure responseto exercise normalized, and arm/leg blood pressures in the upper extremity were higher, gradients were reduced. Patients had no symptomsreranging from 117 to 153 mm Hg; systolic blood pres- lated to atenolol either during the study or on follow-up sures in 9 of 10 patients were above the 95th percentile (now of 24 months), and treadmill endurance times compared with age- and gender-specific normal sub- were unchanged. Cardioselective@blockade would appear to be a safe and effective way to treat exercisejects. Diastolic blood pressureswere unchanged. Arm/ leg gradients were present in 8 patients, ranging from 7 induced upper limb hypertension in this context. to 36 mm Hg (mean 13). The increase in systolic blood Many mechanismshave been proposedas the etiolopressure and in arm/leg gradient before treadmill test- gy of this hypertensive response.Beekman et alI5 deming was attributed to anticipatory anxiety. Peak exercise onstrated altered baroreceptor function in patients who heart rates reached the predicted maximum in all pa- remain hypertensive after satisfactory coarctation retients, ranging from 186 to 202 per minute. Upper ex- pair; this mechanism may contribute to the hypertensive tremity systolic blood pressuresat exercise termination responseto exercise even when resting blood pressures ranged from 201 to 270 mm Hg (mean 229). Arm/leg are normal. Histologically, the aortic wall before coarcgradients increased in all patients with a range of 30 to tation has been shown to be more rigid than the wall below coarctation and this difference may well persist 143 mm Hg and a mean of 84. After /3 blockade with atenolol, resting heart rates after surgical repair. l6 Increasedvascular resistanceand significantly decreased to a mean of 62 per minute abnormal reactivity in the upper extremities, with nor(range 47 to 75 p lO.005). Resting upper extremity mal resistance and reactivity in the lower extremities, blood pressures also significantly decreased to 115 to has been demonstratedlong after coarctation repairi7Js; 143 mm Hg (mean 129). Although this did not reach this could certainly contribute to the hypertensive reOf the 13 potential patients, 10 demonstrated upper extremity systolic blood pressure 2220 mm Hg, or arm/leg gradient 230 mm Hg, or both, with treadmill evaluation. Each patient was begun on atenolol 50 mg once in the morning. Patients were reevaluated within 4 weeks. Resting and exercise heart rates were not decreasedby 25% in 6 patients, so the doseof atenolol was increased until effective ,f3 blockade was achieved. Treadmill blood pressureresults on this final dosageare those reported. Of the 10 patients, 4 were receiving atenolol 50 mg, 1 was receiving 75 mg and 5 were receiving 100 mg at the time of this report.

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Changein Endurancewith Atenolol Treatment

270 260 250 1

2

3

4

5

Patlent

6

7

8

9

10

.

Number

FIGURE 2. Treadmill exercise endurance times in the 10 study patients before and after @blmkade with atenolol.

200 190 180 170 160

FIGURE il. Systolic bleed pressure (BP) at exercise terfflination in the 10 study patients before (1) and after (2) fi blockde with atenokd.

blood pressure after p blockade is due to a decreasein cardiac output mediated almost entirely by the decrease in heart rate, with little if any decreasein stroke volume. Cardioselective @blockade with atenolol has been shown to produce the same hemodynamic response as nonselective 0 blockade with propranolol.20 Potentially important humoral and metabolic effects of nonselective p blockade are avoided by using atenolol. Late follow-up studies after coarctation repair demonstrate important residual problems. In particular, a high incidence of premature cardiovascular diseasehas been well documented, with a significant risk for early mortality even with apparently satisfactory surgical repair.6m9The duration of preoperative hypertension has been identified as a significant risk factor for persistent hypertension and early cardiovascular disease.6j9IHowever, even in patients who have undergone surgery at an early age with a satisfactory resting result, severeupper extremity hypertension with exercise is common. Exercise is used as an analogue for the wide variety of physiologic stressesresulting in increased cardiac output that occur in everyday life. Systolic hypertension is known to be a powerful predictor of cardiovascular morbidity in adults.21,22There would therefore appear to be a good rationale for treatment of an exaggerated systolic hypertensive responseto exercisein patients after coarctation repair, most of whom had considerable systolic hypertension of variable duration before their operations. The results in this small series suggestthat cardioselective p blockage can be used to achieve this result safely and effectively.

sponseto exercise. A minimal residual anatomic narrowing may result in no significant systolic gradient at t: We gratefully ac~owledge the rest as well; however,with the increased cardiac output secretarial assistanceof Terry Howe and Cindy Shearwith exercise, the same mild degree of narrowing can result in a significant gradient and in upper extremity er. hypertension.3J9It seemslikely that some combination of thesemechanismsrepresentsthe etiology of exerciseinduced upper extremity hypertension after satisfactory surgical repair of coarctation. . James FW, Kaplan S. Systolic hypertension during submaximal exercise after Beta blockade is known to produce a powerful sup- correction of coarctaticn of the aorta. Circulation 1974;5O(suppl 11):11-27-1X-34. Connor TM. Evaluation of persistent coarctation of aorta after surgery with pression of the cardiac chronotropic responseto exer- 2.blood pressure measurement and exercise testing. Am .I Car&l 1979;43:74-cise. Concurrently, systolic blood pressureis reduced at 78. rest and at all levels of exercise.Cumming and Mir,lO in 3. Freed MD, Rocchini A, Rosenthal A, Nadas AS, Castaneda AR. Exerciseinduced hypertension after surgical repair of coarctation of the aorta. urn J a catheterization study of patients with coarctation, Car&d 1979;43:253-258. used propranolol to demonstrate that the decrease in 4. Pelech AN, Kartodihardjo W, Balfe JA, Balfe JW, Olley PM, Leenen FHH. THE AMERICAN JOURNAL OF CARDIOLOGY

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