Aortic Insufficiency Requiring Valve Replacement in Whipple’s Disease Creighton B. Wright, M.D., Loren F. Hiratzka, M.D., Stanley Crossland, M.D., Jeffrey Isner, M.D., and Jerry A. Snow, M.D. ABSTRACT Reviews of postmortem reports on patients with Whipple’s disease (intestinal lipodystrophy) describe gross valvular deformity in more than 5O0/o with characteristic histological findings of macrophages containing periodic acid-Schiffpositive, diastase-resistant granules. Frequently, congestive heart failure characterizes the terminal stages. In a 58-year-old man with well-documented Whipple’s disease for 5 years, gastrointestinal,joint, and pericardial involvement apparently resolved with medical therapy. However, 10 years later, severe aortic insufficiency necessitated prosthetic valve replacement, at which time gross and histological examination of the excised valve demonstrated characteristic changes of Whipple’s disease. Clinical recognition of the importance of cardiac valvular abnormalities and of possible late cardiac decompensation mandates close observation of patients with Whipple’s disease. Corrective operation should improve the patient’s chances of survival.
Anatomical heart lesions are reportedly common in Whipple’s disease (intestinal lipodystrophy) [2,3,8,10]. The most common clinical finding is pericardial involvement, demonstrated by friction rubs and electrocardiographic changes [81. Although a variety of valvular and endocardia1 anatomical lesions have been identified in postmortem specimens, they have not been manifest clinically in a situation requiring surgical correction of the lesion. This paper details the clinical course of a patient with known Whipple’s disease who had progressive angina and From the Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, the Department of Surgery, George Washington University Medical Center, the Department of Cardiology, Georgetown University Medical Center, and the Department of Cardiology, Veterans Administration Hospital, Washington, DC. Accepted for publication Oct 19, 1977. Address reprint requests to Dr. Wright, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
aortic valve insufficiency and who required aortic valve replacement. We found no similar case in a review of the literature. A 58-year-old white man was admitted to the Veterans Administration Hospital, Washington, DC, on several occasions during a 10-year period. His medical history included several significant features. The patient had pulmonary tuberculosis from 1941 through 1956. In 1960 he experienced polyarthritis, particularly of the ankles and knees, with recurrent transient episodes during the next 5 years. In 1965 he frequently had stools which were fatty and foul smelling, and also exertional dyspnea with orthopnea and pedal edema, initially attributed to anemia and hypoalbuminemia. He was hospitalized in June, 1965, for persistent gastrointestinal symptoms, at which time diagnosis of intestinal malabsorption was supported by studies with 1311-labeledtriolein and trioleic acid. A chest roentgenogram made at that time showed no cardiac abnormalities. A peroral biopsy of the small intestine revealed mucosal atrophy, numerous dilated lymphatics, and infiltration of the lamina propria with large, foamy macrophages containing periodic acid-Schiff (PAS)-positive, diastase-resistant granules. Therapy was initiated with tetracycline, 1 gm per day. Exertional dyspnea and edema of the lower extremities initially resolved with digitalis and diuretics. However, during this period of hospitalization, the patient had progressive signs of congestive heart failure. A grade 316 holosystolic cardiac murmur was heard at the apex, and there was a loud friction rub at the left sternal border. At this time a chest roentgenogram showed cardiac enlargement, pulmonary venous congestion, and evidence of pleural effusion. With dietary alteration and further diuretic therapy the congestive heart failure cleared, and by the time of discharge in October the patient had only a faint apical sys-
466 0003-4975/78/0025-0517$1.00 @ 1978 by Creighton B. Wright
467 Case Report: Wright et al: Valve Replacement in Whipple's Disease
tolic murmur and no pericardial rub, and the gastrointestinal symptoms had resolved. In June, 1967, he was asymptomatic. A chest roentgenogram showed no cardiomegaly, and a repeat small intestinal biopsy demonstrated improvement in the mucosal pattern and reduction in the number of PAS-positive macrophages. Because of the identification of clinical pericarditis with congestive heart failure which responded to medical management, this case history was reported previously [6]. In 1969 the patient began to have symptoms compatible with angina pectoris. They were stable through the next 4 years, but he required occasional treatment with nitroglycerin. In 1973 the frequency of angina increased, and in early 1974, cardiac catheterization demonstrated 3+ aortic regurgitation and a high-grade lesion of the distal right coronary artery, which was a small, nondominant artery. Left ventricular end-diastolic pressure was 10 mm Hg. Administration of Isordil (isosorbide dinitrate), digoxin, and nitroglycerin resulted in some clinical improvement. On readmission in 1976, the patient had a grade 2/6 systolic ejection murmur and a grade 3/6 diastolic murmur at the left sternal border with radiation to the apex. The chest roentgenogram had not changed. The ECG showed first-degree atrioventricular block and left ventricular hypertrophy with a strain pattern that had not changed since 1974. However, repeat cardiac catheterization demonstrated 4+ aortic regurgitation with a dilated, generally hypokinetic left ventricle. The coronary artery lesion had not altered significantly. Clinically, the patient had progressive angina and signs of progressive cardiac decompensation. Operation was recommended, and on May4,1976, with the assistance of cardiopulmonary bypass, the aortic valve was replaced. The findings at operation were a severe, fibrotic, and adhesive pericarditis compatible with the patient's history of pericarditis in 1965. The epicardium of the heart was encased in thick, yellow fat. The aortic valve leaflets had yellow nodules along the free margin, and the leaflets were rolled so that they did not meet in the midportion (Fig 1).The endocardium was speckled with yellow, fatty streaks. The anterior leaflet of the mitral valve appeared normal. The aortic valve was excised and re-
Fig 1 . lntraoperative photograph shozuing the aortic surface of the aortic valve. Note the nodules and rolling of the free margin of the leaflets, udiich prevent apposition of the leaflets centrally without commissural fusion.
placed with a Bjork-Shiley prosthesis (25 mm) using multiple interrupted mattress sutures of 2-0 Ethiflex buttressed with Teflon pledgets. The patient tolerated this procedure without incident and was discharged on the thirteenth postoperative day. At a follow-up visit fifteen months after the operation, the patient was doing well. There were no signs of congestive heart failure or angina.
Pathological Findings The aortic valve showed focal calcifications and collections of lymphocytes and mononuclear cells as well as proliferation of fibrous tissue. Thickened and sclerotic vessels were seen in the pericardial and valvular tissue. No bacteria were seen. Scattered macrophages containing PASpositive, diastase-resistant granules were present in the pericardial tissue, the aortic valve (Fig 2), and in a biopsy specimen from sternal bone marrow. Comment In 1907, G. H. Whipple [14] described the postmortem findings of a disease "characterized anatomically by the deposits of fat and fatty acids in the intestinal and mesenteric lymphatic
468
The Annals of Thoracic Surgery Vol 25 No 5 May 1978
A
B
Fig 2 . Pliotornicro,pruplis showin
Anatomical heart lesions are reportedly common in Whipple’s disease (intestinal lipodystrophy) [2,3,8,10]. The most common clinical finding is pericardial involvement, demonstrated by friction rubs and electrocardiographic changes [81. Although a variety of valvular and endocardia1 anatomical lesions have been identified in postmortem specimens, they have not been manifest clinically in a situation requiring surgical correction of the lesion. This paper details the clinical course of a patient with known Whipple’s disease who had progressive angina and From the Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, the Department of Surgery, George Washington University Medical Center, the Department of Cardiology, Georgetown University Medical Center, and the Department of Cardiology, Veterans Administration Hospital, Washington, DC. Accepted for publication Oct 19, 1977. Address reprint requests to Dr. Wright, Division of Thoracic and Cardiovascular Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
aortic valve insufficiency and who required aortic valve replacement. We found no similar case in a review of the literature. A 58-year-old white man was admitted to the Veterans Administration Hospital, Washington, DC, on several occasions during a 10-year period. His medical history included several significant features. The patient had pulmonary tuberculosis from 1941 through 1956. In 1960 he experienced polyarthritis, particularly of the ankles and knees, with recurrent transient episodes during the next 5 years. In 1965 he frequently had stools which were fatty and foul smelling, and also exertional dyspnea with orthopnea and pedal edema, initially attributed to anemia and hypoalbuminemia. He was hospitalized in June, 1965, for persistent gastrointestinal symptoms, at which time diagnosis of intestinal malabsorption was supported by studies with 1311-labeledtriolein and trioleic acid. A chest roentgenogram made at that time showed no cardiac abnormalities. A peroral biopsy of the small intestine revealed mucosal atrophy, numerous dilated lymphatics, and infiltration of the lamina propria with large, foamy macrophages containing periodic acid-Schiff (PAS)-positive, diastase-resistant granules. Therapy was initiated with tetracycline, 1 gm per day. Exertional dyspnea and edema of the lower extremities initially resolved with digitalis and diuretics. However, during this period of hospitalization, the patient had progressive signs of congestive heart failure. A grade 316 holosystolic cardiac murmur was heard at the apex, and there was a loud friction rub at the left sternal border. At this time a chest roentgenogram showed cardiac enlargement, pulmonary venous congestion, and evidence of pleural effusion. With dietary alteration and further diuretic therapy the congestive heart failure cleared, and by the time of discharge in October the patient had only a faint apical sys-
466 0003-4975/78/0025-0517$1.00 @ 1978 by Creighton B. Wright
467 Case Report: Wright et al: Valve Replacement in Whipple's Disease
tolic murmur and no pericardial rub, and the gastrointestinal symptoms had resolved. In June, 1967, he was asymptomatic. A chest roentgenogram showed no cardiomegaly, and a repeat small intestinal biopsy demonstrated improvement in the mucosal pattern and reduction in the number of PAS-positive macrophages. Because of the identification of clinical pericarditis with congestive heart failure which responded to medical management, this case history was reported previously [6]. In 1969 the patient began to have symptoms compatible with angina pectoris. They were stable through the next 4 years, but he required occasional treatment with nitroglycerin. In 1973 the frequency of angina increased, and in early 1974, cardiac catheterization demonstrated 3+ aortic regurgitation and a high-grade lesion of the distal right coronary artery, which was a small, nondominant artery. Left ventricular end-diastolic pressure was 10 mm Hg. Administration of Isordil (isosorbide dinitrate), digoxin, and nitroglycerin resulted in some clinical improvement. On readmission in 1976, the patient had a grade 2/6 systolic ejection murmur and a grade 3/6 diastolic murmur at the left sternal border with radiation to the apex. The chest roentgenogram had not changed. The ECG showed first-degree atrioventricular block and left ventricular hypertrophy with a strain pattern that had not changed since 1974. However, repeat cardiac catheterization demonstrated 4+ aortic regurgitation with a dilated, generally hypokinetic left ventricle. The coronary artery lesion had not altered significantly. Clinically, the patient had progressive angina and signs of progressive cardiac decompensation. Operation was recommended, and on May4,1976, with the assistance of cardiopulmonary bypass, the aortic valve was replaced. The findings at operation were a severe, fibrotic, and adhesive pericarditis compatible with the patient's history of pericarditis in 1965. The epicardium of the heart was encased in thick, yellow fat. The aortic valve leaflets had yellow nodules along the free margin, and the leaflets were rolled so that they did not meet in the midportion (Fig 1).The endocardium was speckled with yellow, fatty streaks. The anterior leaflet of the mitral valve appeared normal. The aortic valve was excised and re-
Fig 1 . lntraoperative photograph shozuing the aortic surface of the aortic valve. Note the nodules and rolling of the free margin of the leaflets, udiich prevent apposition of the leaflets centrally without commissural fusion.
placed with a Bjork-Shiley prosthesis (25 mm) using multiple interrupted mattress sutures of 2-0 Ethiflex buttressed with Teflon pledgets. The patient tolerated this procedure without incident and was discharged on the thirteenth postoperative day. At a follow-up visit fifteen months after the operation, the patient was doing well. There were no signs of congestive heart failure or angina.
Pathological Findings The aortic valve showed focal calcifications and collections of lymphocytes and mononuclear cells as well as proliferation of fibrous tissue. Thickened and sclerotic vessels were seen in the pericardial and valvular tissue. No bacteria were seen. Scattered macrophages containing PASpositive, diastase-resistant granules were present in the pericardial tissue, the aortic valve (Fig 2), and in a biopsy specimen from sternal bone marrow. Comment In 1907, G. H. Whipple [14] described the postmortem findings of a disease "characterized anatomically by the deposits of fat and fatty acids in the intestinal and mesenteric lymphatic
468
The Annals of Thoracic Surgery Vol 25 No 5 May 1978
A
B
Fig 2 . Pliotornicro,pruplis showin
