Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.

Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center.

To determine the incidence, nature and subsequent management of complications occurring during right ventricular endomyocardial biopsy in patients with cardiomyopathy, all events occurring during 546 procedures in 464 consecutive patients were prospectively recorded. The internal jugular vein was the primary site of introduction in 96% of cases. A total of 33 complications (6%) occurred: 15 (2.7%) during catheter insertion including 12 arterial punctures (2%), 2 vasovagal reactions (0.4%) and 1 episode of prolonged bleeding (0.2%), all without sequelae; 18 (3.3%) during biopsy included 6 arrhythmias (1.1%), 5 conduction abnormalities (1%), 4 possible perforations (0.7%) and 3 definite perforations (0.5%) (pericardial fluid). Two (0.4%) of the three patients with a perforation died. There was no secular trend in the complication rate, nor were complications associated with specific clinical or hemodynamic characteristics. It is concluded that the overall rate of endomyocardial biopsy complications (6%) is low, but mortality may occur.

Clinicopathologic description of myocarditis.

Histologic evidence of myocarditis was demonstrated in 35 of 348 patients submitted to endomyocardial biopsy over 5 years. Analysis of the histologic findings and clinical course of these patients resulted in a new clinicopathologic classification of myocarditis in which four distinct subgroups are identified. Patients with fulminant myocarditis become acutely ill after a distinct viral prodrome, have severe cardiovascular compromise, multiple foci of active myocarditis by histologic study and ventricular dysfunction that either resolves spontaneously or results in death. Patients with acute, chronic active and chronic persistent myocarditis have a less distinct onset of illness. Patients with acute myocarditis present with established ventricular dysfunction and may respond to immunosuppressive therapy or their condition may progress to dilated cardiomyopathy. Those with chronic active myocarditis initially respond to immunosuppressive therapy, but they have clinical and histologic relapses and develop ventricular dysfunction associated with chronic inflammatory changes including giant cells on histologic study. Chronic persistent myocarditis is characterized by a persistent histologic infiltrate, often with foci of myocyte necrosis but without ventricular dysfunction despite other cardiovascular symptoms such as chest pain or palpitation.

Is atrial activation beneficial in heart transplant recipients?

Because of the distortion of atrial morphology that occurs during cardiac allograft transplantation in humans, the beneficial effects of properly sequenced atrial and ventricular activation are unclear in these patients. To evaluate the atrial contribution to ventricular pump performance in heart transplant recipients, arterial pressure and cardiac output during pacing from either chamber were measured in nine patients 10 +/- 1 days after transplantation. Systolic, diastolic and mean systemic arterial pressures were significantly higher during atrial pacing compared with ventricular pacing: 143 +/- 23 versus 125 +/- 20 mm Hg, 73 +/- 15 versus 66 +/- 14 mm Hg and 94 +/- 17 versus 84 +/- 16 mm Hg, respectively (p less than 0.05 for all). In addition, cardiac output decreased from 5.5 +/- 1.4 to 4.6 +/- 1.5 liters/min (p less than 0.005) for atrial versus ventricular pacing. Thus, there is a significant atrial contribution to cardiac performance in patients after heart transplantation. This may have clinical implications in those patients who later require a permanent pacemaker.

Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy.

Heart-reactive antibodies are commonly observed in patients with myocarditis or cardiomyopathy. Such antibodies may be important in the pathogenesis of these disorders, yet the specific antigens recognized have not been studied systematically. This report characterizes circulating heart autoantibodies from patients with myocarditis (n = 17) or idiopathic cardiomyopathy (n = 71) and from healthy volunteers (n = 15). Indirect immunofluorescence demonstrated that high titer (greater than or equal to 1:20) immunoglobulin G (IgG) antibody activity occurred in 59% of the myocarditis samples, 20% of the cardiomyopathy samples and none of the normal samples. All samples were tested by Western immunoblotting for IgG activity against a normal human heart extract. The number of antigens recognized by each sample was enumerated and the molecular weight of each antigen estimated; the prevalence of reactivity against antigens in selected molecular weight classes was determined. There was no difference in the mean number of heart antigens recognized by serum from each group. For most weight classes, prevalence either did not differ significantly among the various groups or subgroups or was greatest among samples from healthy volunteers. Prevalence of reactivity with 190 to 199 kilodalton (kd) antigens was greatest (p less than 0.05) among low titer serum samples from patients with myocarditis. High titer cardiomyopathy serum differed from normal serum by an increased (p less than 0.05) prevalence of antibodies to 40 to 49 and 100 to 109 kd antigens. These results suggest that western immunostaining may ultimately contribute substantively to identifying patients with myocarditis or cardiomyopathy.

Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus.

OBJECTIVES: The purpose of this study was to characterize the histologic and immunopathologic results of 37 endomyocardial biopsy samples from patients infected with human immunodeficiency virus type 1 (HIV-1) who were evaluated for unexplained global left ventricular dysfunction. BACKGROUND: Recent studies have identified a growing number of patients infected with HIV-1 who develop unexplained left ventricular dysfunction and congestive heart failure. Myocarditis has been confirmed at autopsy in small numbers of such patients, although a pathogenic opportunistic infectious agent can rarely be identified. METHODS: All patients had moderate to severe global left ventricular hypokinesia on two-dimensional echocardiography. Endomyocardial biopsy samples were evaluated by standard histologic studies, immunoperoxidase staining and in situ hybridization for cytomegalovirus and HIV-1 gene sequences. RESULTS: Twenty-eight patients presented with New York Heart Association functional class III or IV congestive heart failure. Four patients had myocarditis secondary to known etiologies (opportunistic infection n = 2; drug-induced hypersensitivity myocarditis n = 2). Of the remaining 33 samples, 17 (51%) showed histologic evidence of idiopathic active or borderline myocarditis. Immunohistologic findings revealed induced expression of major histocompatibility class I antigen on myocytes and increased numbers of infiltrating CD8+ T lymphocytes. Specific hybridization within myocytes was observed in 5 of 33 samples with the HIV-1 antisense riboprobe and in 16 of 33 samples with the cytomegalovirus immediate early (IE-2) antisense riboprobe. All but one patient with specific myocyte hybridization presented with congestive heart failure; all patients had myocarditis and CD4+ cell counts < 100/mm3. CONCLUSIONS: This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.

Echocardiographic findings in fulminant and acute myocarditis.

OBJECTIVES: We sought to use echocardiography to assess the presentation and potential for recovery of left ventricular (LV) function of patients with fulminant myocarditis compared with those with acute myocarditis. BACKGROUND: The clinical course of patients with myocarditis remains poorly defined. We have previously proposed a classification that provides prognostic information in myocarditis patients. Fulminant myocarditis causes a distinct onset of illness and severe hemodynamic compromise, whereas acute myocarditis has an indistinct presentation, less severe hemodynamic compromise and a greater likelihood of progression to dilated cardiomyopathy. METHODS: Echocardiography was performed at presentation and at six months to test the hypothesis that fulminant (n = 11) or acute (n = 43) myocarditis could be distinguished morphologically. RESULTS: Patients with both fulminant (fractional shortening 19 +/- 4%) and acute myocarditis (17 +/- 7%) had LV systolic dysfunction. Patients with fulminant myocarditis had near normal LV diastolic dimensions (5.3 +/- 0.9 cm) but increased septal thickness (1.2 +/- 0.2 cm) at presentation, while those with acute myocarditis had increased diastolic dimensions (6.1 +/- 0.8 cm, p < 0.01 vs. fulminant) but normal septal thickness (1.0 +/- 0.1 cm, p = 0.01 vs. fulminant). At six months, patients with fulminant myocarditis had dramatic improvement in fractional shortening (30 +/- 8%) compared with no improvement in patients with acute myocarditis (19 +/- 7%, p < 0.01 for interaction between time and type of myocarditis). CONCLUSIONS: Fulminant myocarditis is distinguishable from acute myocarditis by echocardiography. Patients with fulminant myocarditis exhibit a substantial improvement in ventricular function at six months compared with those with acute myocarditis. Echocardiography has value in classifying patients with myocarditis and may provide prognostic information.

Ischemic cardiomyopathy: endomyocardial biopsy and ventriculographic evaluation of patients with congestive heart failure, dilated cardiomyopathy and coronary artery disease.

OBJECTIVES: This study was designed to define clinical and pathophysiologic similarities and differences between patients with ischemic and idiopathic dilated cardiomyopathy. BACKGROUND: Significant coronary artery disease in patients with new onset congestive heart failure due to dilated cardiomyopathy has important prognostic and therapeutic implications. METHODS: Clinical, histologic, ventriculographic and hemodynamic features of patients with dilated cardiomyopathy who underwent coronary angiography were reviewed. RESULTS: Patients with ischemic cardiomyopathy (n = 21) compared with those with idiopathic cardiomyopathy (n = 40) had similar presenting symptoms, durations of illness, and coronary risk factor profiles, with the exception of a greater prevalence of cigarette smoking (71% vs. 39%, p = 0.028) and male gender (100% vs. 70%, p = 0.014). Endomyocardial biopsy specimens from patients with ischemic cardiomyopathy demonstrated a greater prevalence of replacement fibrosis (48% vs. 8%, p = 0.001) and a lesser degree of histologically assessed myocyte hypertrophy (mean grade 0.5 +/- 0.7 vs. 1.3 +/- 1.3, p = 0.015). Although ventriculographically determined regional dyskinesia was present in both groups, there was a higher prevalence of two or more adjacent segments in the ischemic cardiomyopathy group (50% vs. 10%, p = 0.03). This ischemic group had hemodynamic variables associated with a worse prognosis: higher pulmonary artery wedge pressure (23 +/- 10 vs. 15 +/- 9 mm Hg, p = 0.006) and lower cardiac index (2.0 +/- 0.5 vs. 2.3 +/- 0.5 liters/min per m2, p = 0.044). Also, in this group, patients had a mean of 2.6 +/- 0.7 diseased vessels; 15 (71%) of 21 patients had triple-vessel disease and 18 (86%) of 21 had at least one occluded or suboccluded artery. CONCLUSIONS: 1) Patients with ischemic and idiopathic cardiomyopathy may be clinically indistinguishable unless coronary angiography is performed. 2) A greater prevalence of replacement fibrosis and a lesser degree of myocardial hypertrophy in patients with ischemic cardiomyopathy may account for the greater extent of hemodynamic decompensation observed at presentation.

The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients.

OBJECTIVES: The purpose of this study was to document the various causes of dilated cardiomyopathy in a large group of adult patients with congestive heart failure. BACKGROUND: Previous reports of the causes of dilated cardiomyopathy have usually been case reports of a single specific etiology or review articles. The frequency of any single specific heart muscle disease is largely unknown. METHODS: We evaluated 673 patients referred for congestive heart failure due to dilated cardiomyopathy. The evaluation included medical history, physical examination, routine blood chemistry and hematologic measurements, electrocardiography and echocardiography. Thyroid function tests, antinuclear antibody tests and urinary vanillylmandelic acid and metanephrine levels were also obtained. Endomyocardial biopsy with right heart catheterization was performed in every patient. Coronary arteriography was performed in patients who had at least two standard cardiovascular risk factors or a history suggestive of myocardial ischemia. The cases were retrospectively reviewed, and a final cause for dilated cardiomyopathy was listed for each patient. RESULTS: The most common causes of dilated cardiomyopathy were idiopathic origin (47%), idiopathic myocarditis (12%) and coronary artery disease (11%). The other identifiable causes of dilated cardiomyopathy made up 31% of the total cases. CONCLUSIONS: Idiopathic dilated cardiomyopathy is a common cause of congestive heart failure. Specific heart muscle diseases occur with much less frequency.

Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: a nonhistologic marker of myocarditis.

The histologic diagnosis of active myocarditis is frequently difficult to establish. A nonhistologic marker of immune activation would be clinically useful in identifying cases of immune-mediated myocarditis. A viral etiology with subsequent autoimmunity to cardiac antigens has been implicated in human myocarditis. Because autoimmunity and viral disease are commonly associated with increased expression of major histocompatibility complex (MHC) antigens on targeted tissue, we examined endomyocardial biopsy samples from patients with active myocarditis for abnormal levels of MHC antigen expression. Thirteen patients with active myocarditis and eight control patients with other well-defined cardiac diagnoses (coronary disease, amyloidosis or neoplasm) were studied. A sensitive radioimmunoassay was developed that utilized monoclonal antibodies to human MHC class I and class II antigens in order to quantitate the expression of both of these antigens within each biopsy. Abnormal MHC class I and class II antigen expression was present in 11 of 13 myocarditis specimens and 1 of 8 control samples (specificity 88%, sensitivity 84.6%). Active myocarditis samples had approximately a 10-fold increase in MHC class I and class II expression. Immunoperoxidase staining localized abnormal MHC expression primarily within microvascular endothelium and along myocyte surfaces (11 of 13). This study is the first to demonstrate a marked increase in major histocompatibility complex antigen expression within the myocardium of patients with active myocarditis. The identification of abnormal histocompatibility antigen expression within an endomyocardial biopsy may prove a useful adjunct to the histologic diagnosis of myocarditis.

Acute nifedipine withdrawal: consequences of preoperative and late cessation of therapy in patients with prior unstable angina.

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic predictors of acute cardiac rejection in human endomyocardial biopsies: a multivariate analysis.

To identify specific histologic abnormalities that could predict early cardiac rejection before the development of myocyte necrosis, 167 consecutive endomyocardial biopsy samples from 18 cardiac transplant recipients were retrospectively analyzed and 17 histologic variables were semiquantitatively graded from 0 to 3. Forty-five biopsy samples contained foci of myocyte necrosis and were labeled Rejectors. The two samples immediately preceding Rejector biopsies were labeled Predictors (n = 44). All remaining samples were labeled Others (n = 78). Endocardial and interstitial infiltrates, interstitial mononuclear cells, pyroninophilic mononuclear cells, polymorphonuclear leukocytes and other cells (eosinophils and plasma cells) were significantly increased in graded severity in Rejector biopsy samples as compared with Predictors or Others (p less than 0.001, ANOVA testing). These variables cannot distinguish Predictor biopsy specimens from Others. On the other hand, interstitial edema, perivascular karyorrhexis and perivascular infiltrate with intermyocyte extension are histologic abnormalities that can distinguish Predictor biopsy samples from Others (p less than 0.001, ANOVA testing). Multiple logistic regression analysis indicates that the relative risk of developing myocyte necrosis when a biopsy sample contains interstitial edema is 8.1. With perivascular infiltrate with intermyocyte extension in addition, the relative risk is 41.4. In summary, three histologic abnormalities have been identified that help predict the future development of myocyte necrosis within the next two endomyocardial biopsies. Biopsy specimens with these abnormalities probably represent early cardiac rejection before the development of myocyte necrosis.

Prognostic cardiac catheterization variables in survivors of acute myocardial infarction: a five year prospective study.

The prognostic variables from predischarge coronary angiography and left ventriculography in survivors of acute myocardial infarction during the years 1974 to 1978 were evaluated in 143 patients (less than or equal to 66 years of age) with documented myocardial infarction who were then followed up prospectively for 5 years. One half of the study population had triple vessel coronary disease (greater than or equal to 50% stenosis). However, only 7% of patients had severely depressed left ventricular function with an ejection fraction less than or equal to 29%. Evaluation of the contribution of many clinical and angiographic variables to a first cardiac event (death, nonfatal reinfarction or coronary artery bypass surgery) was considered with Kaplan-Meier actuarial curves and multivariate Cox's hazard function analysis. A risk segment was defined as an area of contracting myocardium supplied by a coronary artery with a greater than 50% stenosis. Multivariate analysis demonstrated that right plus left anterior descending coronary artery stenoses (p less than 0.01), ejection fraction (p less than 0.01) and the presence of risk segments (p less than 0.05) were significant predictors of outcome. Furthermore, on separate multivariate analyses, the angiographic variables added significantly to the clinical variables to predict cardiac events over 5 years of follow-up. Therefore, in survivors of acute myocardial infarction who undergo cardiac catheterization, additive prognostic information is obtained that can be used to stratify risk over 5 years.

Early discharge following acute myocardial infarction. Long-term follow-up of randomized patients.

Long-term follow-up was obtained on 138 patients who participated in a prospective, randomized study comparing two weeks with three weeks of hospitalization following uncomplicated acute myocardial infarction. Follow-up information was available on 123 (89%) of all randomized patients. The mean follow-up period was 35 months for those patients who died and 99 months for those who survived. No differences were found between the two groups with respect to survival, cardiac-related deaths, frequency or severity of angina pectoris, subsequent myocardial infarction, incidence of congestive heart failure, number of ventricular aneurysms, or subsequent medical therapy. A significantly greater number of survivors in both groups stopped smoking and had a normal initial heart size than those who died. This long-term follow-up study further supports the conclusions of earlier short-term studies that two weeks of hospitalization is safe in patients with uncomplicated acute myocardial infarction.

In situ detection of human cytomegalovirus immediate-early gene transcripts within cardiac myocytes of patients with HIV-associated cardiomyopathy.

OBJECTIVE: Recent clinical and echocardiographic studies have identified dilated cardiomyopathy in 10-20% of HIV-infected adults. The purpose of this study was to determine the role of cardiotropic cytomegalovirus (CMV) infection in the development of HIV-associated cardiomyopathy. DESIGN: We generated sense and antisense digoxigenin-labeled riboprobes derived from the CMV immediate-early (IE) and delayed-early (DE) genes and applied them retrospectively to endomyocardial biopsy samples and control autopsy cardiac samples from HIV-infected patients. SETTING: Tertiary care, referral hospital. PATIENTS: Twelve consecutive HIV-infected patients with global left ventricular hypokinesis demonstrated on two-dimensional echocardiography; eight randomly selected control autopsy cardiac samples from HIV-infected patients without cardiac disease during life. MEASUREMENTS AND MAIN RESULTS: Of the 12 endomyocardial biopsy specimens, six (50%) were found to have specific myocyte nuclear and perinuclear hybridization for transcripts of the CMV IE gene, consistent with non-permissive or latent infection. Similar patterns were not found in any of the eight autopsy control samples. All six patients presented with unexplained congestive heart failure and had CD4 counts less than 100 x 10(6)/l; all six biopsy samples had immunohistochemical evidence of increased myocardial major histocompatibility complex (MHC) class I expression, a finding typical of non-HIV myocarditis. None of the endomyocardial biopsy samples had characteristic CMV inclusions and no specific hybridization was noted with the DE gene riboprobe, suggesting that no active viral DNA replication was present. Only two of the six patients with myocyte hybridization with the IE riboprobe had clinical evidence of solid organ infection with CMV at the time of cardiovascular presentation. CONCLUSIONS: This study is the first to demonstrate the expression of the IE gene of CMV within myocytes from HIV-infected patients with cardiomyopathy, suggesting a non-permissive infection of myocytes without classical intranuclear inclusions. Myocyte infection may be necessary to trigger cellular and humoral-mediated cardiac injury and may be best identified using in situ hybridization techniques.

The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients.

This report describes the evaluation of 1,278 patients referred to The Johns Hopkins Hospital with dilated cardiomyopathy. After a careful history and physical examination, selected laboratory tests, and endomyocardial biopsy, a specific diagnosis was made in 49% of cases. In 16% of cases the biopsy demonstrated a specific histologic diagnosis. Myocarditis and coronary artery disease were the most frequent specific diagnoses; 51% of patients were classified as idiopathic. Thus a rigorous and systematic search can demonstrate an underlying cause for approximately one-half of patients with unexplained cardiomyopathy. Endomyocardial biopsy plays a crucial role in this evaluation. Six cases are presented which demonstrate the utility of endomyocardial biopsy in specific clinical situations. In addition to its routine use in monitoring rejection in heart transplant recipients, endomyocardial biopsy is indicated in the evaluation of possible infiltrative cardiomyopathy, in differentiating restrictive cardiomyopathy from constrictive pericarditis, and in diagnosing and monitoring doxorubicin cardiotoxicity. The importance of diagnosing myocarditis remains controversial, and disagreement persists about the utility of immunosuppressive therapy in these patients. A combination of clinical and histologic features can divide patients with myocarditis into 4 subgroups--acute, fulminant, chronic active, and chronic persistent. This classification provides prognostic information and may identify those patients who may respond to immunosuppression, as well as those likely to have adverse outcomes from such treatment. The continued development of novel molecular techniques may allow endomyocardial biopsy to provide greater prognostic and therapeutic information in the future.

Relationship between corticosteroid exposure and plasma lipid levels in heart transplant recipients.

PURPOSE: Accelerated coronary atherosclerosis is a major cause of heart graft failure two years and more after heart transplantation, yet its etiology remains undetermined. We conducted this study to determine the prevalence of coronary risk-associated lipid abnormalities, and the relationship between lipid levels and exposure to corticosteroids and cyclosporine, in heart transplant recipients. PATIENTS AND METHODS: The records of 92 consecutive heart transplant recipients from three different transplantation centers were reviewed. Patients from the three centers varied in age, in corticosteroid regimens, and in the proportion undergoing transplantation for ischemic cardiomyopathy. Although 11 patients were not receiving corticosteroids at the time of the study, all patients had received them immediately after transplantation. In addition to information pertaining to demographics, pretransplant medical history, rejection episodes, drug doses, renal function, and blood glucose levels, data on dietary intake and body weight were collected and plasma lipid levels were measured at the time of record review. RESULTS: A significant number, 48 (52 percent), of heart transplant recipients were above the sex- and age-adjusted 75th percentile, and 35 (38 percent) were above the 90th percentile for total cholesterol in comparison with a general reference population. Similar elevations were found in low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Bivariate analysis demonstrated cumulative prednisone exposure (r = 0.40, p = 0.0001) and cumulative cyclosporine exposure (r = 0.22, p = 0.04) but not diet or etiology of pretransplant heart disease to be significantly associated with age- or sex-adjusted total cholesterol percentiles. Low-density lipoprotein cholesterol percentiles were also correlated with cumulative prednisone (r = 0.37, p = 0.001) and cumulative cyclosporine exposure (r = 0.24, p = 0.02). Stepwise multiple linear regression analysis, however, demonstrated cumulative prednisone exposure to be the strongest predictor of both total and low-density lipoprotein cholesterol levels and percentiles (p = 0.0001), independent of cumulative cyclosporine exposure and other clinical variables. CONCLUSION: These data suggest that long-term corticosteroid exposure may result in an increased prevalence of unfavorable lipid profiles in heart transplant recipients.

Chronic active myocarditis following acute Bartonella henselae infection (cat scratch disease).

An association between Bartonella infection and myocardial inflammation has not been previously reported. We document a case of a healthy young man who developed chronic active myocarditis after infection with Bartonella henselae (cat scratch disease). He progressed to severe heart failure and underwent orthotopic heart transplantation. Bartonella henselae, therefore, should be included among the list of infectious agents associated with chronic active myocarditis.

Peritransplant injury to the myocardium associated with the development of accelerated arteriosclerosis in heart transplant recipients.

Accelerated arteriosclerosis is now the major long-term complication of heart transplantation. Defining the risk factors associated with the development of accelerated arteriosclerosis will provide not only a means of identifying patients at risk for this complication but also clues to the etiology of accelerated arteriosclerosis. The purpose of this study was to examine the relationship between peritransplant myocardial ischemic injury and the development of accelerated arteriosclerosis. In a case-control study we examined the first three endomyocardial biopsies from 50 heart transplant recipients and graded the degree of ischemic injury present in these biopsies. The histologic changes graded in the biopsies included contraction band necrosis, coagulative necrosis, and macrophagic removal of ischemically injured myocytes. Of the 50 recipients included in the study, 25 had angiographic evidence of accelerated arteriosclerosis and 25 did not. In multivariate analysis, which included the number of class I major histocompatibility (MHC) antigen mismatches between the donor and the recipient, the recipient's post-transplant cytomegalovirus status, the donor's age, and the number of rejection episodes, the histologic degree of ischemic injury present in the biopsies emerged as the strongest predictor of the development of accelerated arteriosclerosis (RR 2.6, 95% CI 1.2-5.8, p = 0.02). These results suggest that ischemic injury to the heart during the peritransplant period significantly contributes to the development of accelerated arteriosclerosis in heart transplant recipients and that histologic changes in early posttransplant biopsies can be used to identify recipients at risk of developing accelerated arteriosclerosis.

Pseudo-graft-versus-host disease in heart and heart-lung recipients.

Autopsies from nine patients who had received a cardiac allograft transplant and one with a combined heart-lung transplant were assessed for histologic evidence of pseudo-graft-versus-host disease (pseudo-GVHD). Five of the ten patients had GVHD-like changes in two or more tissues, including prominent lymphocyte-associated bile duct injury consistent with marked hepatic pseudo-GVHD and mild cutaneous changes resembling GVHD. A sixth recipient had marked changes in the liver, but autopsy restrictions prevented examination of the skin. A seventh recipient had only mild pseudo-GVHD changes limited to the skin. In contrast, a series of six patients who were candidates for cardiac transplant had no specific pathologic changes suggesting pseudo-GVHD. The majority of those with pseudo-GVHD had received nonirradiated blood product transfusions, raising the possibility of posttransfusion engraftment and GVHD. Unlike the posttransfusion GVHD, however, two of the six developed GVHD-related complications late with a latent period of five and 9.5 months, and two recipients received no transfusions. All were receiving only modest doses of immunosuppressive agents at the time they developed liver function abnormalities, including low or tapering doses of cyclosporine (CsA). In some of these recipients, therefore, the pseudo-GVHD changes may well represent an autoimmune reaction resembling the post-CsA model of autoimmune disease.