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Treatment of end-stage cardiac failure with growth hormone
THE LANCET
to improve cardiac function and increase ventricular mass in patients with dilated cardiomyopathy and mild CHF.1 Highdose GH in the long-term has drawbacks.4 Our data suggest that GH may have acute effects on the heart in patients with CHF, comparable to those of dobutamine and phosphodiesterase inhibitors in the absence of any sympathetic activation.5 GH may have a place among inotropic drugs in the short-term treatment of CHF. This research has been partly supported by the Centro Studi e Ricerche di Neuroendocrinologia, Brescia, and funded by current research grant of “Salvatore Maugeri” Foundation. We thank F Barbieri and P Paoletti (Eli Lilly, Italy), and A Giordano and C Poiesi (Gussago and Brescia, Italy). 1
2
3
4 5
Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 334: 809–14. Giustina A, Boni E, Romanelli G, Grassi V, Giustina G. Cardiopulmonary performance during exercise in acromegaly, and the effects of acute suppression of growth hormone hypersecretion with octreotide. Am J Cardiol 1995; 75: 1042–47. Giustina A, Lorusso R, Borghetti V, Bugari G, Misitano V, Alfieri O. Impaired spontaneous growth hormone secretion in severe dilated cardiomyopathy. Am Heart J 1996; 131: 629–32. Turner H, Wass JAH. Growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 335: 672. Grose R, Strain J, Greenberg M, LeJemtel TH. Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure. J Am Coll Cardiol 1986; 7: 1107–13.
Variable
Patient 1 Baseline
Baseline
6 weeks HGH
3 months post
Weight (kg)
58
64
55
59
Sum of 8 skinfolds (mm)
76·9
99
93·9
99·3
105·8
425·6
445·4
421·8
435·7
446·5
30 32
36 36
Sum of 9 girths (cm) Hand grip strength (kg) Left Right
.. ..
.. ..
63
.. ..
Sum of 7 strengths
..
..
119
157
200
Heart rate (per min) At rest Max exercise
102 112
101 121
92 123
91 141
86 145
79 77
76 78
88 98
72 84
68 90
..
25
20
..
4500
2250
..
Mean BP (mm Hg) At rest Max exercise Pulmonary artery wedge pressure (mm Hg)
..
SVR index (dyn s cm–5 m2)
..
..
Cardiac index (Lmin–1m–2)
..
..
LV dimensions (mm) End diastolic End systolic
.. ..
.. ..
Ejection fraction (%)
..
Exercise duration (min)
Endocrine Section, University of Brescia, 25123 Brescia, Italy (A Giustina); Cardiac Surgery, Spedali Civili, Brescia; and Salvatore Maugeri Foundation, IRCCS Rehabilitation Institute, Division of Cardiology, Gussago
Patient 2 1 week HGH
Max O2 consumption (mL kg–1min–2)
.. 7·7
..
2·55
9·5 ..
2·8
..
70 65
65 54
.. ..
6
12
..
9·3
16·4
18·4
9·8
17·6
19·6
BP=blood pressure, SVR=systemic vascular resistance.
Influence of growth hormone on anthropometric, functional, cardiac, and hormonal characteristics
Treatment of end-stage cardiac failure with growth hormone J G O’Driscoll, D J Green, M Ireland, D Kerr, R I Larbalestier
Human growth hormone (HGH) improves haemodynamics, myocardial energy metabolism, and clinical status in patients with moderate congestive heart failure.1 In addition, HGH reverses cachexia in patients with AIDS, malignancy, liver disease, and congestive cardiac failure, though this last patient was HGH-deficient due to hypopituitarism.2 It seems likely that the combined anabolic and cardiac effects of HGH would benefit patients with severe heart failure and cardiac cachexia. We report two patients with severe cardiac cachexia as a result of ischaemic heart disease who were treated with recombinant HGH (Somatropin, Serono, Australia). The first patient, a 59-year-old man, had had heart failure for more than 8 months and required intermittent support with inotropes despite digoxin, diuretics, and an angiotensin-converting enzyme (ACE) inhibitor. Before HGH treatment, he had generalised cachexia, was New York Heart Association class IV, wheel-chair bound, weighed 57·75 kg, and had body-mass index of 19·2 kg/m2. The second patient, a 52-year-old man, developed severe heart failure subsequent to myocardial infarction, which persisted despite coronary artery bypass surgery. After 4 months in heart failure the patient was stabilised with maximally tolerated doses of digoxin, diuretics, an ACE inhibitor, and vasodilators. This patient also had generalised cachexia, was New York Heart Association class IV, weighed 55 kg, and had a body-mass index of 22 kg/m2. The first patient received 14 units of recombinant HGH subcutaneously per day and was reassessed after 7 days, whereas the second patient received 10 units per day and was reassessed after 6 weeks. Measures from patient 2 were also collected 3 weeks after cessation of HGH. Body weight increased in both
1068
patients, along with the sum of 8 skinfolds and the sum of 9 muscle girths (table), suggesting that the weight gain was attributable to increased muscle bulk and subcutaneous adipose tissue. Patient 1 demonstrated improved grip strength and exercise duration during a maximal exercise test, whereas maximal strength measures on a variety of compound exercises, VO2 max, and exercise duration improved substantially in patient 2. These data suggest improved functional capacity and exercise tolerance, which were maintained or continued to improve 3 weeks after cessation of therapy in patient 2. In addition, maximum heart rate during exercise increased in both patients, suggesting improved myocardial function which was confirmed in patient 2 by echocardiography, right-heart catheterisation, and gated blood pool scan. Following HGH therapy, patient 1 was successfully bridged to transplantation and patient 2 improved to such a degree that he was delisted. The results of these studies suggest that HGH administration to patients with severe heart failure and cardiac cachexia has a beneficial effect which may be sustained after stopping HGH. However, the results of these case studies must be interpreted with caution, since spontaneous improvement in functional and haemodynamic capacity cannot be ruled out. Nonetheless, we suggest that the present results provide support for a randomised placebo-controlled study of HGH in patients with severe heart failure. 1
2
Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomopathy. N Engl J Med 1996; 334: 809–14. Cuneo RC, Wilmshurst P, Lowy C, McGauley G, Sönksen PH. Cardiac failure responding to growth hormone. Lancet 1989; i: 838–39.
Cardiac Transplant Unit, Royal Perth Hospital, Perth 6001, Western Australia (J G O’Driscoll); and Department of Human Movement, University of Western Australia
Vol 349 • April 12, 1997
to improve cardiac function and increase ventricular mass in patients with dilated cardiomyopathy and mild CHF.1 Highdose GH in the long-term has drawbacks.4 Our data suggest that GH may have acute effects on the heart in patients with CHF, comparable to those of dobutamine and phosphodiesterase inhibitors in the absence of any sympathetic activation.5 GH may have a place among inotropic drugs in the short-term treatment of CHF. This research has been partly supported by the Centro Studi e Ricerche di Neuroendocrinologia, Brescia, and funded by current research grant of “Salvatore Maugeri” Foundation. We thank F Barbieri and P Paoletti (Eli Lilly, Italy), and A Giordano and C Poiesi (Gussago and Brescia, Italy). 1
2
3
4 5
Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 334: 809–14. Giustina A, Boni E, Romanelli G, Grassi V, Giustina G. Cardiopulmonary performance during exercise in acromegaly, and the effects of acute suppression of growth hormone hypersecretion with octreotide. Am J Cardiol 1995; 75: 1042–47. Giustina A, Lorusso R, Borghetti V, Bugari G, Misitano V, Alfieri O. Impaired spontaneous growth hormone secretion in severe dilated cardiomyopathy. Am Heart J 1996; 131: 629–32. Turner H, Wass JAH. Growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996; 335: 672. Grose R, Strain J, Greenberg M, LeJemtel TH. Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure. J Am Coll Cardiol 1986; 7: 1107–13.
Variable
Patient 1 Baseline
Baseline
6 weeks HGH
3 months post
Weight (kg)
58
64
55
59
Sum of 8 skinfolds (mm)
76·9
99
93·9
99·3
105·8
425·6
445·4
421·8
435·7
446·5
30 32
36 36
Sum of 9 girths (cm) Hand grip strength (kg) Left Right
.. ..
.. ..
63
.. ..
Sum of 7 strengths
..
..
119
157
200
Heart rate (per min) At rest Max exercise
102 112
101 121
92 123
91 141
86 145
79 77
76 78
88 98
72 84
68 90
..
25
20
..
4500
2250
..
Mean BP (mm Hg) At rest Max exercise Pulmonary artery wedge pressure (mm Hg)
..
SVR index (dyn s cm–5 m2)
..
..
Cardiac index (Lmin–1m–2)
..
..
LV dimensions (mm) End diastolic End systolic
.. ..
.. ..
Ejection fraction (%)
..
Exercise duration (min)
Endocrine Section, University of Brescia, 25123 Brescia, Italy (A Giustina); Cardiac Surgery, Spedali Civili, Brescia; and Salvatore Maugeri Foundation, IRCCS Rehabilitation Institute, Division of Cardiology, Gussago
Patient 2 1 week HGH
Max O2 consumption (mL kg–1min–2)
.. 7·7
..
2·55
9·5 ..
2·8
..
70 65
65 54
.. ..
6
12
..
9·3
16·4
18·4
9·8
17·6
19·6
BP=blood pressure, SVR=systemic vascular resistance.
Influence of growth hormone on anthropometric, functional, cardiac, and hormonal characteristics
Treatment of end-stage cardiac failure with growth hormone J G O’Driscoll, D J Green, M Ireland, D Kerr, R I Larbalestier
Human growth hormone (HGH) improves haemodynamics, myocardial energy metabolism, and clinical status in patients with moderate congestive heart failure.1 In addition, HGH reverses cachexia in patients with AIDS, malignancy, liver disease, and congestive cardiac failure, though this last patient was HGH-deficient due to hypopituitarism.2 It seems likely that the combined anabolic and cardiac effects of HGH would benefit patients with severe heart failure and cardiac cachexia. We report two patients with severe cardiac cachexia as a result of ischaemic heart disease who were treated with recombinant HGH (Somatropin, Serono, Australia). The first patient, a 59-year-old man, had had heart failure for more than 8 months and required intermittent support with inotropes despite digoxin, diuretics, and an angiotensin-converting enzyme (ACE) inhibitor. Before HGH treatment, he had generalised cachexia, was New York Heart Association class IV, wheel-chair bound, weighed 57·75 kg, and had body-mass index of 19·2 kg/m2. The second patient, a 52-year-old man, developed severe heart failure subsequent to myocardial infarction, which persisted despite coronary artery bypass surgery. After 4 months in heart failure the patient was stabilised with maximally tolerated doses of digoxin, diuretics, an ACE inhibitor, and vasodilators. This patient also had generalised cachexia, was New York Heart Association class IV, weighed 55 kg, and had a body-mass index of 22 kg/m2. The first patient received 14 units of recombinant HGH subcutaneously per day and was reassessed after 7 days, whereas the second patient received 10 units per day and was reassessed after 6 weeks. Measures from patient 2 were also collected 3 weeks after cessation of HGH. Body weight increased in both
1068
patients, along with the sum of 8 skinfolds and the sum of 9 muscle girths (table), suggesting that the weight gain was attributable to increased muscle bulk and subcutaneous adipose tissue. Patient 1 demonstrated improved grip strength and exercise duration during a maximal exercise test, whereas maximal strength measures on a variety of compound exercises, VO2 max, and exercise duration improved substantially in patient 2. These data suggest improved functional capacity and exercise tolerance, which were maintained or continued to improve 3 weeks after cessation of therapy in patient 2. In addition, maximum heart rate during exercise increased in both patients, suggesting improved myocardial function which was confirmed in patient 2 by echocardiography, right-heart catheterisation, and gated blood pool scan. Following HGH therapy, patient 1 was successfully bridged to transplantation and patient 2 improved to such a degree that he was delisted. The results of these studies suggest that HGH administration to patients with severe heart failure and cardiac cachexia has a beneficial effect which may be sustained after stopping HGH. However, the results of these case studies must be interpreted with caution, since spontaneous improvement in functional and haemodynamic capacity cannot be ruled out. Nonetheless, we suggest that the present results provide support for a randomised placebo-controlled study of HGH in patients with severe heart failure. 1
2
Fazio S, Sabatini D, Capaldo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomopathy. N Engl J Med 1996; 334: 809–14. Cuneo RC, Wilmshurst P, Lowy C, McGauley G, Sönksen PH. Cardiac failure responding to growth hormone. Lancet 1989; i: 838–39.
Cardiac Transplant Unit, Royal Perth Hospital, Perth 6001, Western Australia (J G O’Driscoll); and Department of Human Movement, University of Western Australia
Vol 349 • April 12, 1997