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For Gold, Heart Rate Matters
For Gold, Heart Rate Matters Jean-François Surmely, MD, Paul Mohacsi, MD, Jean-Paul Schmid, MD, Thierry Carrel, MD, Etienne Delacretaz, MD A 19-year-old woman presented with decreased exercise tolerance 3 years after orthotopic heart transplantation. Exercise capacity was severely reduced, with a maximal workload of 84 W, corresponding to 56% of the predicted value. After exclusion of other causes, insufficient heart rate response to exercise was considered as the major contributor to her decreased exercise tolerance. Correction of this problem with the implantation of an AAIR pacemaker dramatically improved her physical performance, allowing her to win 5 gold medals at the European Heart and Lung Transplant Games. This case report illustrates how pacemaker therapy can dramatically improve the symptoms and performance of patients with chronotropic incompetence. J Heart Lung Transplant 2005;24: 1171–3. Copyright © 2005 by the International Society for Heart and Lung Transplantation.
CASE REPORT A 19-year-old woman was evaluated 3 years after orthotopic heart transplantation because of severely decreased exercise tolerance. She had been a member of the junior Swiss swimming team and had developed rapidly progressive and refractory heart failure due to dilated cardiomyopathy at the age of 16. Because of persistent shock caused by a low output state, treatment with a biventricular assist device had been necessary for 9 days until heart transplantation was performed. The post-operative follow-up had been uneventful, except for persistent fatigue and reduced exercise tolerance. She felt especially limited by the inability to suddenly increase her level of physical activity. The patient participated in a rehabilitation program without substantial improvement. On clinical examination, heart and lung auscultation was normal, and there were no signs of heart failure (e.g., due to cardiac rejection). Blood test results revealed mild normocytic anemia, with a hemoglobin value of 108 g/liter, a hematocrit of 0.32, and erythrocytes of 3.46 T/liter, with mean cell volume of 91 fl and a mean cellular hemoglobin concentration of 341 g/liter. Serum levels of plasma creatinine, electrolytes, C-reactive protein, and thyroid hormones were normal. A chest X-ray revealed normal lung and heart structures. A 12-lead electrocardiogram (ECG) showed sinus rhythm at 80 beats/min and normal PQ interval and QRS From the Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland. Submitted November 24, 2004; revised November 30, 2004; accepted January 14, 2005. Reprint requests: Paul Mohacsi, MD, Swiss Cardiovascular Center Bern, University Hospital, CH-3010 Bern, Switzerland. Telephone: ⫹ 41 31 632 21 11. Fax: ⫹41 31 632 42 99. E-mail: paul.mohacsi@ insel.ch Copyright © 2005 by the International Society for Heart and Lung Transplantation. 1053-2498/05/$–see front matter. doi:10.1016/ j.healun.2005.01.008
complexes. Follow-up coronary angiography revealed no signs of transplant vasculopathy. Transthoracic echocardiography showed a mild increase in the left ventricular mass index (124 g/m2) and mild impairment of diastolic function, but systolic function was normal. Lung function tests were (percent of predicted value): total lung capacity, 4.1 liters (71%); vital capacity, 2.7 liters (63%); residual volume, 1.43 liters (90%); forced expiratory volume in 1 second (FEV1), 2.5 liters (63%); and FEV1/forced vital capacity, 94%. Diffusion of carbon monoxide corrected for hemoglobin and alveolar ventilation was normal. A 24-hour ambulatory ECG showed stable sinus rhythm with no bradycardia and no pause. Maximal, mean, and minimum heart rates were 120, 85, and 75 beats/min, respectively. During cardiopulmonary exercise testing, exercise capacity was severely reduced, with a peak oxygen uptake of 20.6 ml/kg/min (57% of predicted value) and a maximal workload of 84 W, corresponding to 56% of the predicted value (Figure 1). Anaerobic threshold was reached at a rate of oxygen consumption (VO2) of 14.2 ml/kg/min (69% of peak VO2), and the maximal respiratory exchange ratio was 1.11. The normal pulmonary adaptation to exercise, the lack of an arterial oxygen desaturation during exercise, and a breathing reserve that was 40 liters/min at test termination argued against a pulmonary limitation of exercise capacity. Striking was the delayed and blunted heart rate response during exercise, from 81 beats/min to 103 beats/min (51% of predicted value) (Figure 1 circles) with a heart rate reserve of only 22 beats/min, typical of heart denervation physiology. A single-chamber AAIR pacemaker was implanted 31 months after transplantation. Subsequently, the patient described considerable improvement in her exercise capacity that contributed to an improvement of her quality of life. During an exercise stress test 2 weeks after pacemaker implantation, exercise duration in1171
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Figure 1. Cardiopulmonary exercise stress test on a bicycle ergometer with a ramp protocol (work load increase 10 W/min) shows a chronotropic incompetence with a virtually missing heart rate increase during the early exercise phase before pacemaker implantation. After pacemaker implantation and AAIR stimulation, adequate heart rate response, both at exercise initiation and during workload increase, follows a normal slope of work rate/oxygen uptake of approximately 1:10. Markedly increased exercise time and oxygen uptake during stimulation (dots, before; triangles, after pacemaker implantation). (*The body weight of the patient is 60 kg)
creased from 6:15 to 10:00 minutes, and peak oxygen uptake reached 26.4 ml/kg/min (77% of the predicted value) (Figure 1). Peak power output was 111 W, and anaerobic threshold was reached at a VO2 of 18.5 ml/kg/min (70% of peak VO2). Her heart rate rapidly increased from 81 to 170 beats/min, according to the programmed rate response (Figure 1 triangles). The systolic and diastolic blood pressures increased from 100/65 to 185/75 mm Hg. After this test, the patient resumed swim training. Blinded to the pacemaker settings, she did the 100-m crawl in 101 seconds vs 95 seconds with the pacemaker first programmed AAI at 30 beats/min and then AAIR at 60 to 170 beats/min, respectively. Seven weeks after pacemaker implantation, she took part in the European Heart and Lung Transplant Games in Dublin, Ireland and won 5 gold medals by winning the 50-m and 100-m
crawl in 35 and 90 seconds, respectively; the 50-m and 100-m backstroke in 44 seconds and 105 seconds, respectively; and the 50-m breaststroke in 45 seconds (Figure 2). In summary, AAIR pacing allowed a 22% increase in maximal oxygen uptake, from 20.6 to 26.4 ml/kg/min, an 32% increase in maximal power output, and an improvement in swimming performances with a 6% reduction in racing time. The patient felt an important difference with the ability to suddenly increase the level of physical activity in her daily life, and that contributed to a relevant improvement in quality of life. DISCUSSION Initially, permanent pacemakers were often implanted in orthotopic cardiac transplant recipients for sinus node dysfunction. It has subsequently become clear
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that sinus node function improves with time after transplantation and that implantation of a permanent pacemaker is not warranted in most patients.1 However, after cardiac denervation, an increase in heart rate during exercise is mainly caused by an increase in plasma catecholamine concentration. This results in a delayed and blunted heart rate response during exercise that can be symptomatic in a few patients. Although reduced exercise capacity after heart transplantation may have multiple causes, including physical deconditioning, steroid-induced myopathy, denervated heart physiology, and altered peripheral blood flow response to exercise, this case illustrates that chronotropic incompetence per se can be an important factor limiting exercise capacity and quality of life. Correction of this factor with AAIR pacing can dramatically improve physical performance and may be worth gold. In conclusion, this case emphasizes the importance of heart rate response to exercise and illustrates how pacemaker therapy can dramatically improve the symptoms and performance of patients with chronotropic incompetence. REFERENCE
Figure 2. The winner of 5 gold medals.
1. Holt ND, McComb JM. Cardiac transplantation and pacemakers: when and what to implant. Card Electrophysiol Rev 2002;6:140 –51.
CASE REPORT A 19-year-old woman was evaluated 3 years after orthotopic heart transplantation because of severely decreased exercise tolerance. She had been a member of the junior Swiss swimming team and had developed rapidly progressive and refractory heart failure due to dilated cardiomyopathy at the age of 16. Because of persistent shock caused by a low output state, treatment with a biventricular assist device had been necessary for 9 days until heart transplantation was performed. The post-operative follow-up had been uneventful, except for persistent fatigue and reduced exercise tolerance. She felt especially limited by the inability to suddenly increase her level of physical activity. The patient participated in a rehabilitation program without substantial improvement. On clinical examination, heart and lung auscultation was normal, and there were no signs of heart failure (e.g., due to cardiac rejection). Blood test results revealed mild normocytic anemia, with a hemoglobin value of 108 g/liter, a hematocrit of 0.32, and erythrocytes of 3.46 T/liter, with mean cell volume of 91 fl and a mean cellular hemoglobin concentration of 341 g/liter. Serum levels of plasma creatinine, electrolytes, C-reactive protein, and thyroid hormones were normal. A chest X-ray revealed normal lung and heart structures. A 12-lead electrocardiogram (ECG) showed sinus rhythm at 80 beats/min and normal PQ interval and QRS From the Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland. Submitted November 24, 2004; revised November 30, 2004; accepted January 14, 2005. Reprint requests: Paul Mohacsi, MD, Swiss Cardiovascular Center Bern, University Hospital, CH-3010 Bern, Switzerland. Telephone: ⫹ 41 31 632 21 11. Fax: ⫹41 31 632 42 99. E-mail: paul.mohacsi@ insel.ch Copyright © 2005 by the International Society for Heart and Lung Transplantation. 1053-2498/05/$–see front matter. doi:10.1016/ j.healun.2005.01.008
complexes. Follow-up coronary angiography revealed no signs of transplant vasculopathy. Transthoracic echocardiography showed a mild increase in the left ventricular mass index (124 g/m2) and mild impairment of diastolic function, but systolic function was normal. Lung function tests were (percent of predicted value): total lung capacity, 4.1 liters (71%); vital capacity, 2.7 liters (63%); residual volume, 1.43 liters (90%); forced expiratory volume in 1 second (FEV1), 2.5 liters (63%); and FEV1/forced vital capacity, 94%. Diffusion of carbon monoxide corrected for hemoglobin and alveolar ventilation was normal. A 24-hour ambulatory ECG showed stable sinus rhythm with no bradycardia and no pause. Maximal, mean, and minimum heart rates were 120, 85, and 75 beats/min, respectively. During cardiopulmonary exercise testing, exercise capacity was severely reduced, with a peak oxygen uptake of 20.6 ml/kg/min (57% of predicted value) and a maximal workload of 84 W, corresponding to 56% of the predicted value (Figure 1). Anaerobic threshold was reached at a rate of oxygen consumption (VO2) of 14.2 ml/kg/min (69% of peak VO2), and the maximal respiratory exchange ratio was 1.11. The normal pulmonary adaptation to exercise, the lack of an arterial oxygen desaturation during exercise, and a breathing reserve that was 40 liters/min at test termination argued against a pulmonary limitation of exercise capacity. Striking was the delayed and blunted heart rate response during exercise, from 81 beats/min to 103 beats/min (51% of predicted value) (Figure 1 circles) with a heart rate reserve of only 22 beats/min, typical of heart denervation physiology. A single-chamber AAIR pacemaker was implanted 31 months after transplantation. Subsequently, the patient described considerable improvement in her exercise capacity that contributed to an improvement of her quality of life. During an exercise stress test 2 weeks after pacemaker implantation, exercise duration in1171
1172
Surmely et al.
The Journal of Heart and Lung Transplantation August 2005
Figure 1. Cardiopulmonary exercise stress test on a bicycle ergometer with a ramp protocol (work load increase 10 W/min) shows a chronotropic incompetence with a virtually missing heart rate increase during the early exercise phase before pacemaker implantation. After pacemaker implantation and AAIR stimulation, adequate heart rate response, both at exercise initiation and during workload increase, follows a normal slope of work rate/oxygen uptake of approximately 1:10. Markedly increased exercise time and oxygen uptake during stimulation (dots, before; triangles, after pacemaker implantation). (*The body weight of the patient is 60 kg)
creased from 6:15 to 10:00 minutes, and peak oxygen uptake reached 26.4 ml/kg/min (77% of the predicted value) (Figure 1). Peak power output was 111 W, and anaerobic threshold was reached at a VO2 of 18.5 ml/kg/min (70% of peak VO2). Her heart rate rapidly increased from 81 to 170 beats/min, according to the programmed rate response (Figure 1 triangles). The systolic and diastolic blood pressures increased from 100/65 to 185/75 mm Hg. After this test, the patient resumed swim training. Blinded to the pacemaker settings, she did the 100-m crawl in 101 seconds vs 95 seconds with the pacemaker first programmed AAI at 30 beats/min and then AAIR at 60 to 170 beats/min, respectively. Seven weeks after pacemaker implantation, she took part in the European Heart and Lung Transplant Games in Dublin, Ireland and won 5 gold medals by winning the 50-m and 100-m
crawl in 35 and 90 seconds, respectively; the 50-m and 100-m backstroke in 44 seconds and 105 seconds, respectively; and the 50-m breaststroke in 45 seconds (Figure 2). In summary, AAIR pacing allowed a 22% increase in maximal oxygen uptake, from 20.6 to 26.4 ml/kg/min, an 32% increase in maximal power output, and an improvement in swimming performances with a 6% reduction in racing time. The patient felt an important difference with the ability to suddenly increase the level of physical activity in her daily life, and that contributed to a relevant improvement in quality of life. DISCUSSION Initially, permanent pacemakers were often implanted in orthotopic cardiac transplant recipients for sinus node dysfunction. It has subsequently become clear
The Journal of Heart and Lung Transplantation Volume 24, Number 8
Surmely et al.
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that sinus node function improves with time after transplantation and that implantation of a permanent pacemaker is not warranted in most patients.1 However, after cardiac denervation, an increase in heart rate during exercise is mainly caused by an increase in plasma catecholamine concentration. This results in a delayed and blunted heart rate response during exercise that can be symptomatic in a few patients. Although reduced exercise capacity after heart transplantation may have multiple causes, including physical deconditioning, steroid-induced myopathy, denervated heart physiology, and altered peripheral blood flow response to exercise, this case illustrates that chronotropic incompetence per se can be an important factor limiting exercise capacity and quality of life. Correction of this factor with AAIR pacing can dramatically improve physical performance and may be worth gold. In conclusion, this case emphasizes the importance of heart rate response to exercise and illustrates how pacemaker therapy can dramatically improve the symptoms and performance of patients with chronotropic incompetence. REFERENCE
Figure 2. The winner of 5 gold medals.
1. Holt ND, McComb JM. Cardiac transplantation and pacemakers: when and what to implant. Card Electrophysiol Rev 2002;6:140 –51.