A contemporary case series of lupus myocarditis.

OBJECTIVES: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE). METHODS: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM. RESULTS: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%-40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization. CONCLUSIONS: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.

Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis.

Coronary atherosclerosis is frequently associated with calcification of arterial plaque. To understand the mechanisms responsible for the formation of atherosclerotic calcification, we examined human coronary arteries for the presence and extent of mineral. In sections stained specifically for mineral, staining was diffuse and present in all atherosclerotic plaques. Hydroxyapatite was not detected in normal coronary artery sections. Distribution of hydroxyapatite coincided with a similar distribution of calcium detected by a radiodense pattern using contact microradiography of the same sections before cytochemical staining. By energy-dispersive x-ray microanalysis, the chemical composition of calcified sites was identical to hydroxyapatite (Ca10[PO4]6[OH]2), the major inorganic component of bone. Osteopontin is a phosphorylated glycoprotein with known involvement in the formation and calcification of bone and is regulated by local cytokines. Human coronary artery segments (14 normal and 34 atherosclerotic) obtained at autopsy were evaluated immunohistochemically using polyclonal antibodies generated against human osteopontin. Immunohistochemistry for osteopontin indicated intense, highly specific staining in the outer margins of all diseased segments at each calcification front; staining was evident throughout the entire plaque. Conversely, arterial segments free of atheroma and calcification and sections treated with nonimmune serum had no evidence of positive staining. Osteopontin, a protein involved in mineralization is specifically associated with calcific coronary atheroma and may play an important role in the onset and progression of this disease in human coronary arteries. The deposition of noncollagenous proteins such as osteopontin may regulate the presence or absence of calcification and ultimately alter vessel compliance.

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves.

Dystrophic mineralization remains the leading cause of stenotic or regurgitant failure in native human and porcine bioprosthetic heart valves. We hypothesized that cellular expression of noncollagenous matrix proteins (osteopontin, osteocalcin, and osteonectin) that regulate skeletal mineralization may orchestrate valvular calcification. Porcine bioprosthetic heart valves and native human heart valves obtained during replacement surgery were analyzed for cells, matrix proteins that regulate mineralization, and vessels. Cell accumulation and calcification were correlated for both valve types (rho = 0.75, P = 0.01, native; rho = 0.42, P = 0.08, bioprosthetic). Osteopontin expression correlated with cell accumulation (rho = 0.58, P = 0.04) and calcification (rho = 0.52, P = 0.06) for bioprosthetic valves. Osteocalcin expression correlated with calcification (rho = 0.77, P = 0.04) and cell accumulation (rho = 0.69, P = 0.07) in native valves. Comparisons of calcified versus noncalcified native and bioprosthetic valves for averaged total matrix protein mRNA signal score revealed increased noncollagenous proteins mRNA levels in calcified valves (P = 0.07, group I vs. group II; P = 0.02, group III vs. group IV). When stratified according to positive versus negative mRNA signal status, both calcified bioprosthetic valves (P = 0.03) and calcified native valves (P = 0.01) were significantly more positive for noncollagenous proteins mRNA than their noncalcified counterparts. Local cell-associated expression of proteins regulating mineralization suggests a highly coordinated mechanism of bioprosthetic and native valve calcification analogous to physiologic bone mineralization. Modulation of cellular infiltration or cellular expression of matrix proteins that regulate mineralization, may offer an effective therapeutic approach to the prevention of valve failure secondary to calcification.

Cloning and sequencing of a full length cDNA encoding ovine lipoprotein lipase.

A cDNA clone encoding lipoprotein lipase has been isolated from an ovine adipocyte library. Sequencing of this clone has revealed a single open reading frame encoding a 450 amino acid protein. Comparison with known LPL sequences from other species shows a high degree of conservation in the sequence of the protein and in the 5' untranslated region of the DNA sequence.

Clinical profile and outcome of idiopathic restrictive cardiomyopathy.

BACKGROUND: Idiopathic restrictive cardiomyopathy is a poorly recognized entity of unknown cause characterized by nondilated, nonhypertrophied ventricles with diastolic dysfunction resulting in dilated atria and variable systolic function. METHODS AND RESULTS: Between 1979 and 1996, 94 patients (61% women) 10 to 90 years old (mean, 64 years) met strict morphological echocardiographic criteria for idiopathic restrictive cardiomyopathy, mainly dilated atria with nonhypertrophied, nondilated ventricles. None had known infiltrative disease, hypertension of >5 years' duration, or cardiac or systemic conditions associated with restrictive filling. Nineteen percent were in NYHA class I, 53% in class II, and 28% in class III or IV. Atrial fibrillation was noted in 74% of patients and systolic dysfunction in 16%. Follow-up (mean, 68 months) was complete for 93 patients (99%). At follow-up, 47 patients (50%) had died, 32 (68%) of cardiovascular causes. Four had heart transplantation. The death rate compared with actuarial statistics was significantly higher than expected (P<0.0001). Kaplan-Meier 5-year survival was 64%, compared with expected survival of 85%. Multivariate analysis using proportional hazards showed that the risk of death approximately doubles with male sex (hazard ratio [HR] = 2.1), left atrial dimension >60 mm (HR = 2.3), age >70 years (HR = 2.0), and each increment of NYHA class (HR = 2.0). CONCLUSIONS: Idiopathic restrictive cardiomyopathy or nondilated, nonhypertrophic ventricles with marked biatrial dilatation, as defined morphologically by echocardiography, affects predominantly elderly patients but can occur in any age group. Patients present with systemic and pulmonary venous congestion and atrial fibrillation and have a poor prognosis, particularly men >70 years old with higher NYHA class and left atrial dimension >60 mm.

Sudden unexpected death in children and adolescents.

To determine the incidence and clinicopathologic spectrum of sudden unexpected death, we reviewed the death certificate of all residents of Olmsted County, Minnesota who were between 1 and 22 years of age when they died during the period from January 1950 to October 1982. Of 515 death certificates reviewed, 12 (2.3%) recorded sudden unexpected death, resulting in an incidence of 1.3 per 100,000 patient-years. The subjects ranged in age from 3 to 20 years (median 13); 8 of the 12 were male. Of the 12 deaths, 4 were definitely cardiac-related and 3 were probably cardiac-related. In the five other cases, the cause of death was unknown. Three of the 12 subjects had a history of syncope; 2 of the 3 had syncope associated with exercise, and both died while exercising. The relative rarity of sudden unexpected death in children and adolescents probably precludes population screening techniques to identify subjects at risk. However, a subset of subjects with 1) exercise-associated syncope, 2) nonvasodepressor syncope, 3) a family history of sudden unexpected death, or 4) a family history of hypertrophic cardiomyopathy deserves extensive and thorough evaluation.

Regression in thromboembolic type of primary pulmonary hypertension during 2 1/2 years of antithrombotic therapy.

Primary pulmonary hypertension carries a poor prognosis, with a 5 year survival rate of less than 25%. However, a previous study of more than 100 patients with tissue-proved primary pulmonary hypertension suggested that antithrombotic therapy may have a beneficial effect on survival, especially in patients with the thromboembolic type of primary pulmonary hypertension. This report describes a 54 year old white man with primary pulmonary hypertension of the thromboembolic type (proved by right upper lobe lung biopsy) who, after long-term antithrombotic therapy, showed resolution of symptoms of dyspnea and fatigue, regression of electrocardiographic signs of right ventricular hypertrophy and regression of elevated pulmonary artery pressure. Base-line cardiac catheterization in January 1982 revealed elevated pulmonary artery pressure (104/37 mm Hg) and pulmonary vascular resistance (14.6 units/m2) that did not decrease with 100% oxygen or intravenous hydralazine (12 mg). The patient was treated with warfarin and dipyridamole, 100 mg four times daily. The most recent cardiac catheterization in January 1984 revealed a pulmonary artery pressure of 50/15 mm Hg and a pulmonary vascular resistance of 8.7 units/m2. It is believed that this is the first report of regression of the symptoms and signs of biopsy-proved primary pulmonary hypertension. In view of the lack of a response to vasodilators in 1982, it is suggested that antithrombotic therapy is partially responsible for the improvement of this patient.

Frequency and location of prominent left ventricular trabeculations at autopsy in 474 normal human hearts: implications for evaluation of mural thrombi by two-dimensional echocardiography.

The frequency and location of prominent left ventricular trabeculations were studied in 474 autopsy specimens from subjects evenly distributed by sex and age. These structures were observed in 323 (68%) of the hearts, and their frequency was similar in male (72%) and female (65%) subjects. Neither the frequency nor the location varied appreciably with age. Among the 323 hearts with prominent left ventricular trabeculations, 172 (53%) exhibited 2 or more; thus, the total number of trabeculations was 582. Of these 582 trabeculations, 493 (85%) were septoparietal bundles that inserted into both the free wall and the septum. Trabeculations also were observed between two points on the ventricular septum in 37 (6%) of the hearts and between two points along the free wall in 36 (6%). Less common patterns included trabeculations between the ventricular septum and the posteromedial papillary muscle in 10 hearts (2%), the ventricular septum and the anterolateral papillary muscle in 2, the free wall and the posteromedial papillary muscle in 2, the two papillary muscles in 1 and the apex and the ventricular septum in 1. Accordingly, prominent left ventricular trabeculations are considered to be common variants of the normal human heart. Their size, shape and location may lead to their being misinterpreted, possibly as mural thrombi, by two-dimensional echocardiography.

Cor triatriatum dexter: two-dimensional echocardiographic diagnosis.

Cor triatriatum dexter is a malformation resulting from lack of normal regression of the embryonic right valve of the sinus venosus. In this situation, the right atrium is divided by a membrane into two chambers. Two-dimensional echocardiography was used in the antemortem diagnosis of this rare cardiac anomaly in a neonate. Associated cardiac lesions were also documented. The patient died, and findings were verified at autopsy.

Idiopathic lymphoplasmacytic aortic valvulitis: observations in two elderly women with unexplained aortic insufficiency.

Two patients with a unique aortic valvulitis required aortic valve replacement. Both were elderly women who presented with evidence of systemic disease, including fever, arthralgia, myalgia, markedly elevated erythrocyte sedimentation rate, anemia, leukocytosis, hypoalbuminemia and renal insufficiency, in addition to progressive subacute aortic insufficiency. Histologic examination of the excised aortic valve revealed a lymphoplasmacytic infiltrate. Neither patient had evidence of other diseases that have been associated with aortic insufficiency. One should consider the judicious use of glucocorticosteroids for such patients.

Pathology of the cardiac conduction system in myotonic dystrophy: a study of 12 cases.

In 12 autopsy cases of myotonic dystrophy, the most frequently observed histopathologic lesions of the cardiac conduction system were fibrosis, fatty infiltration and atrophy. Fibrosis involved the sinus node in 6 cases, atrioventricular (AV) node in 7, AV bundle in 8, bundle branches in 10 and ventricular myocardium in 11. Fatty infiltration was observed in the sinus node in two cases, AV node in two, AV bundle in six, bundle branches in one and ventricular myocardium in nine. Atrophy was prominent in the AV bundle in five and bundle branches in eight. Lymphocytes infiltrated the conduction system in three cases and were associated with myotonic dystrophy in two and varicella myocarditis in one. Ventricular myocytes were hypertrophied in seven cases, vacuolated in three and exhibited disarray in two. The distribution and extent of conduction system lesions tended to correspond to antemortem electrocardiographic abnormalities, including prolonged PR interval in six cases, intraventricular conduction delay in six and bundle branch block in four. Cardiac involvement by myotonic dystrophy may have contributed to sudden death in four cases.

Electrohydraulic shock wave decalcification of stenotic aortic valves: postmortem and intraoperative studies.

Decalcification of stenotic aortic valves is limited by the difficulty in removing sufficient calcium to restore valve function without cusp perforation. The present study demonstrates that electrohydraulic shock waves generated by a hand-held lithotriptor fragmented the calcifications contained within the cusps of four necropsy specimens of stenotic aortic valves. The electrohydraulic shock waves appeared to create a cleavage plane between the valve tissue and the fragmented calcific deposits, allowing the fragmented calcified masses to be removed without cusp perforation. Five patients with severe aortic stenosis also underwent successful aortic valve decalcification augmented by electrohydraulic shock waves generated with the hand-held lithotriptor, without significant complication. The shock waves permitted removal, from the aortic valve, of calcium that had not been removed by mechanical means. These results indicate that the addition of electrohydraulic shock waves to mechanical aortic valve decalcification may facilitate successful decalcification in patients undergoing operative treatment for aortic stenosis and may allow patients to avoid the need for aortic valve replacement.

Myocardial ischemia in patients with pulmonary atresia and intact ventricular septum.

Children who die after operation for pulmonary atresia and intact ventricular septum may have myocardial ischemia. The relation between histologic evidence of myocardial ischemic injury and the presence of a right ventricle to coronary artery fistula, coronary artery dysplasia and operation in 17 autopsy specimens was assessed. Age at death ranged from 1 day to 16 years (median, 11 days). Of the 17 hearts, 6 (35%) had right ventricle to coronary artery fistulas, 5 of which had coronary artery dysplasia. In three cases, there was segmental or complete absence of a coronary artery. Ischemia was present in four of these six hearts, two of which had right ventricular outflow reconstruction. Six of the 11 hearts without right ventricle to coronary artery fistulas also had myocardial ischemia. Of these six cases, four had right ventricular outflow reconstruction and two had shunt operations. Death occurred from 1 to 8 days (mean 3) after operation. Hearts with pulmonary atresia and intact ventricular septum may have myocardial ischemia with or without either right ventricle to coronary artery fistulas or coronary artery dysplasia. Myocardial ischemia may occur after right ventricular outflow reconstruction or shunt operations. Thus, myocardial ischemia occurs commonly in patients with pulmonary atresia and intact ventricular septum and is not always related to coronary abnormalities or operation.

Incidence and distribution of left ventricular false tendons: an autopsy study of 483 normal human hearts.

The incidence and distribution of left ventricular false tendons were studied in a series of 483 autopsy specimens of human hearts from subjects evenly distributed by sex and age. False tendons were observed in 265 specimens (55%), and their incidence was greater in hearts from male than from female subjects (61 versus 49%; p less than 0.01). Neither the incidence nor the location of false tendons varied appreciably with age. Of the 265 specimens containing false tendons, 100 (38%) exhibited 2 or more, such that the total number of false tendons identified was 414. Of these 414, 272 (66%) were located between the posteromedial papillary muscle and the ventricular septum, 49 (12%) between the two papillary muscles, 47 (11%) between the anterolateral papillary muscle and the ventricular septum, 38 (9%) between the free wall and the septum and 3 (less than 1%) between two aspects of the free wall; 5 (1%) had three or more points of insertion and formed weblike structures. False tendons are common anatomic variants of the normal human left ventricle which may be detected by two-dimensional echocardiography and should not be misinterpreted as pathologic structures such as flail mitral chordae tendineae or mural thrombi.

Cardiac rupture, a clinically predictable complication of acute myocardial infarction: report of 70 cases with clinicopathologic correlations.

OBJECTIVE: To test the hypothesis that certain clinical events may precede free wall myocardial rupture and allow its prediction, we conducted a retrospective and prospective study of 70 patients with rupture. BACKGROUND: Rupture of the left ventricular free wall develops in approximately 10% of patients with fatal acute transmural myocardial infarction. Clinically, its occurrence has been considered precipitous and unexpected. Pathologically, however, rupture appears to be a stuttering, progressive process characterized in many instances by an infiltrating intramural hemorrhage and a thrombus within the tear of > or = 1 day's duration. METHODS: The clinical course and evolutionary electrocardiographic (ECG) changes in 70 consecutive patients with rupture and 100 comparison patients with acute myocardial infarction but without rupture were reviewed to ascertain whether certain clinical symptoms, signs and ECG alterations occur in patients prone to develop rupture, allowing its anticipation. In addition, a correlation was established between the site of infarction indicated by the ECG and the site of rupture determined at autopsy or surgery. RESULTS: Patients with rupture had a significantly greater incidence of pericarditis, repetitive emesis and restlessness and agitation than did patients without rupture. More than 80% of patients with rupture had two or more symptoms compared with 3% of patients without rupture (p < 0.002). A deviation from the expected evolutionary T wave pattern occurred in 94% of patients with rupture and 34% of control patients (p < or = 0.02). An abrupt transient episode of hypotension and bradycardia, probably due to the initial tearing of the epicardium with a resultant small hemopericardium, was observed in 21% of patients with rupture. Rupture of the midlateral wall was most common (32%) and usually occurred in the setting of an inferoposterolateral infarction related to an acute left circumflex artery occlusion. On the basis of these clinical and ECG changes, rupture was confirmed by echocardiography and pericardiocentesis in the two most recent patients, and the defect was successfully repaired. CONCLUSIONS: Rupture is often preceded by particular symptoms, signs--namely, one or more episodes of abrupt, transient hypotension and bradycardia and unexpected alterations of the T waves, especially directional changes of the latter. Patients displaying these symptoms, signs and ECG changes require a bedside echocardiogram and echocardiographically guided pericardiocentesis if fluid is visualized. If the pericardiocentesis identifies the fluid as blood, immediate surgery is indicated.

Diagnosis of lipomatous hypertrophy of the atrial septum by two-dimensional echocardiography.

Originally described in 1964, lipomatous hypertrophy of the atrial septum currently remains a diagnosis established primarily at autopsy. Clinical interest in this disorder has centered on the reported association with supraventricular arrhythmias and sudden death. Because two-dimensional echocardiography allows detailed assessment of atrial septal configuration, we reviewed two-dimensional echocardiographic reports obtained over a 1 year period and identified 17 patients who had features consistent with lipomatous hypertrophy of the atrial septum. Nine were men and the average age was 70 years. Autopsy confirmation of the echographic findings was possible in one patient. In nine patients, ideal body weight was exceeded by 10% or more. The atrial septum viewed from the subcostal transducer position showed a distinctive echo-dense globular thickening sparing the valve of the fossa ovalis. The resultant tomographic image of the atrial septum had a characteristic dumbbell appearance. The mean thickness of the atrial septum was 21 mm (range 15 to 29). Seven patients had supraventricular arrhythmias, and eight had P wave abnormalities. The two-dimensional echocardiographic features described are distinctive and suggest that this technique is the procedure of choice not only for establishing the diagnosis of lipomatous hypertrophy of the atrial septum but also for providing a means for prospective follow-up of patients with this little known entity.

Polymeric stenting in the porcine coronary artery model: differential outcome of exogenous fibrin sleeves versus polyurethane-coated stents.

OBJECTIVES: In a porcine coronary model, fibrin film soaked for 3 h in heparin was used as a circumferential coating on a tantalum stent to assess the effect of this naturally occurring biopolymer on arterial healing. The results were compared with those obtained with medical grade polyurethane-coated stainless steel stents. BACKGROUND: Thrombus plays an important role in healing after arterial injury and may affect the development of neointimal hyperplasia. Manipulation of the initial thrombus may alter the healing response. To study this, we placed a template of fibrin in a porcine coronary artery restenosis model. METHODS: Thirty-four fibrin film stents were delivered in 20 swine. Oversizing was avoided, to prevent deep arterial injury, by placement of optimally sized stents. Initial patency of the stented vessel was confirmed by angiography. RESULTS: Three fibrin-stented swine died within 48 h; in each, the stent was occluded with a fibrin/red blood cell mass. In two of these three, a portion of the exogenous fibrin had become detached from the stent and partially occluded the lumen. Of the remaining 31 stents, all were patent at elective sacrifice at 28 days. Eighty-four percent had a diameter stenosis < 50%, and the mean (+/- SD) diameter stenosis was 32.3 +/- 13%. There was no evidence of significant foreign-body giant-cell reaction. These results contrasted with the medical grade polyurethane-coated stents placed according to the same protocol without oversizing. Twelve of these stents were placed; six swine died of thrombotic occlusion within the 1st 48 h. At elective sacrifice at 28 days, the remaining polyurethane-coated stents were occluded by marked neointimal hyperplasia. CONCLUSIONS: Fibrin film-coated stents seem promising as a template for modifying the local response to arterial injury and for potentially decreasing restenosis rates.

Differential histopathology of primary atherosclerotic and restenotic lesions in coronary arteries and saphenous vein bypass grafts: analysis of tissue obtained from 73 patients by directional atherectomy.

Vascular tissue obtained using a directional percutaneous atherectomy device was examined microscopically. Tissue was obtained from coronary arteries without prior instrumentation (primary lesions, n = 31), aortocoronary saphenous vein bypass grafts with primary lesions (n = 8), coronary arteries with lesions developing after prior balloon angioplasty or mechanical atherectomy (restenotic lesions, n = 30) and vein bypass grafts with restenotic lesions (n = 4). Primary lesions were characterized by dense intimal fibrosis with necrotic debris (83% of intimal tissue) and foam cells typical of atherosclerosis. These lesions frequently contained cholesterol crystals (45% of coronary arteries, 50% of vein grafts) and calcium deposits (65% of coronary arteries, 38% of vein grafts). Restenotic lesions were characterized by an increased proportion of loose fibroproliferative tissue (45% of coronary artery intima, 35% of vein graft intima). Immunohistochemical stains confirmed this proliferative tissue to be primarily smooth muscle cells. Thrombus was rarely observed. Comparison of resected tissues indicated that dense fibrosis and necrosis are significantly more common in primary than in restenotic lesions (83% versus 56% of intimal tissue, p = 0.0005), whereas smooth muscle cell hyperplasia is more common in restenotic than in primary lesions (44% versus 17% of intimal tissue, p less than 0.0005). Partial-thickness resection of medial tissue or full-thickness resection of media with associated adventitial tissue occurred in 27 (56%) of 39 primary atheromatous lesions and 16 (47%) of 34 restenotic lesions; subintimal tissue obtained from primary lesions appeared identical to that obtained from restenotic lesions. These data indicate that the histopathologic characteristics of the neointimal layer of restenotic lesions differ from those of the intimal layer of primary atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Coexistent pulmonary and portal hypertension: morphologic and clinical features.

Patients with portal hypertension of varying etiology may develop pulmonary artery hypertension. In the present autopsy study, pulmonary and hepatic tissue was studied in 12 patients in whom pulmonary and portal hypertension coexisted. Plexogenic pulmonary arteriopathy was present in 10 patients, 7 of whom had coexistent thromboembolic lesions. One patient had isolated medial hypertrophy, which may be an early stage in the plexogenic category, whereas isolated thromboembolic pulmonary vascular disease was observed in one subject. Hepatic disease was consistent with alcoholic cirrhosis in seven patients, cryptogenic cirrhosis in four and extrahepatic portal hypertension without cirrhosis in one. Thrombocytopenia was present in all 10 patients whose platelet count was determined. This study suggests that pulmonary hypertension associated with portal hypertension commonly has a plexogenic appearance on histologic examination. However, thrombosis (whether embolic or in situ) may also contribute to vascular obstruction.

Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy.

In each heart taken from autopsies of 14 men with idiopathic hemochromatosis, the conduction system, atria and 10 sites in the ventricles were histologically graded for stainable iron. Stainable iron was exclusively sarcoplasmic; none was observed in the interstitium. The histologic grade for the same anatomic site varied among hearts and among different anatomic sites in the same heart. Ten hearts had stainable iron in all ventricular sites; one of the three hearts from patients who had undergone therapeutic phlebotomy had no iron at any site. Seven hearts had iron in the atria but at a lesser grade than that found in the ventricles; six hearts had mild focal iron deposition in the atrioventricular conduction system. None of the 14 hearts had stainable iron in the sinus node. Elemental iron was quantitated by atomic absorption spectroscopy in ventricular specimens contiguous to those studied histologically and also in age-matched control hearts. Elemental iron content was markedly increased in hearts with idiopathic hemochromatosis compared with control hearts (p less than 0.01). The quantity of elemental iron varied greatly, similar to stainable iron, but was highest subepicardially. Among the hearts from the 11 patients without prior phlebotomy, three had no stainable iron in the right ventricular septal subendocardium, suggesting that sampling error may be a problem in the evaluation of hemochromatosis by endomyocardial biopsy. The sarcoplasmic location of the iron indicates that cardiac involvement in idiopathic hemochromatosis represents a storage disease and not an infiltrative process; this finding is consistent with the normal ventricular wall thicknesses observed.