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Biomedical subjects

A Herskowitz

Publications and source records attributed to A Herskowitz.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dilated heart muscle disease associated with HIV infection.

As more effective therapies have produced longer survival times for HIV-infected patients, non-infectious complications of late stage HIV infection such as the development of severe global left ventricular dysfunction (dilated heart muscle disease) have emerged. The demographic and clinical characteristics of HIV-infected patients who develop dilated heart muscle disease as well as potential risk factors are, as yet, poorly characterized. Of 174 patients enrolled in a prospective longitudinal study, a total of nine patients, all with CD4 T cell counts < 200 mm-3, developed symptomatic heart disease (congestive heart failure n = 7, sudden cardiac death n = 1 and cardiac tamponade n = 1); three of these patients developed progressive cardiac dysfunction leading to primary cardiac failure and death. An additional 55 HIV-infected patients referred to our Cardiomyopathy Service were found to have global left ventricular dysfunction, with 84% having New York Heart Association Class III or IV congestive heart failure on presentation. Clinical characteristics associated with severe symptomatic cardiac dysfunction included low CD4 T cell counts, myocarditis associated with non-permissive cardiotropic virus infection on endomyocardial biopsy and persistent elevation of anti-heart antibodies. No relationships to any specific HIV risk factor or opportunistic infection were found. These findings suggest that a severe form of HIV-related dilated heart muscle disease is largely a disease of late stage HIV infection. Virus-related myocarditis and cardiac autoimmunity may play a role in the pathogenesis of progressive cardiac injury. Long-term longitudinal studies of larger HIV-infected cohorts are warranted to identify clinical, behavioral and immunologic risk factors.

Adult↗
PubMed1995

Cytokine mRNA expression in postischemic/reperfused myocardium.

While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion. These results provide evidence for local expression of cytokine mRNA in postischemic myocardium and suggest that regulation of local cytokine release is altered during the postischemic period.

Animals↗
PubMed1994

Neutrophil adhesion and complement inhibition prolongs survival of cardiac xenografts in discordant species.

Hyperacute rejection results in rapid destruction of a discordant cardiac xenograft and is characterized by antibody deposition, complement activation, and platelet aggregation. The importance of neutrophils is unclear. Complement inhibition prolongs discordant cardiac xenograft survival. The purpose of this experiment was to determine the relative roles of complement and neutrophils. Selective inhibition of complement and neutrophil adhesion was used in a guinea pig-to-Lewis rat cardiac heterotopic xenotransplant model. NPC 15669 (N-[9H-(2,7-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine), a member of a new class of antiinflammatory agents termed leumedins, specifically prevents recruitment of neutrophils at inflammatory foci by inhibiting upregulation of the CD11b/CD18 adhesion molecule. Soluble complement receptor type 1 (sCR1, BRL 55730) is a potent inhibitor of the alternative and classical complement pathways. Group I (n = 13) received saline vehicle i.v. Group II (n = 15) was treated with NPC 15669 (10 mg/kg i.v. bolus) prior to reperfusion. Group III (n = 13) was treated with sCR1 (20 mg/kg i.v. bolus) prior to reperfusion. Group IV (n = 13) received both NPC 15669 and sCR1. Two xenografts were harvested at each interval time point (Groups I and II, 1, 2, 4, and 6 min; and Groups III and IV, 6, 15, 30, and 60 min). The remainder were followed to cessation of graft function. Graft survival was significantly increased in group IV and group III-375 +/- 13.4 min (mean +/- SD) and 112 +/- 29.4, respectively (P < .05), compared with 9.9 +/- 6.3 in group II and 8.7 +/- 4.9 in group I. Extreme interstitial hemorrhage and edema and contraction band injury were present in group I-III animals at end-stage, and neutrophil infiltration in group III. In group IV grafts, there was a decrease in these parameters despite the longer survival time, and at end-stage rejection the cellular infiltrate was primarily mononuclear. This study demonstrates that complement is an important mediator in early xenograft HYP injury. Combined treatment with NPC 15669 and sCR1 results in reduced histologic injury at all time points and longer graft survival than with sCR1 alone. These results suggest that neutrophil and complement activation play synergistic roles in the pathogenesis of xenograft hyperacute rejection. Neutrophil inhibition may prove to be an important component of multimodality therapy for hyperacute rejection, particularly in less-discordant transplants.

Animals↗
PubMed1994

The absence of constitutive and induced expression of critical cell-adhesion molecules on human cardiac myocytes. Its role in transplant rejection.

Fetal human cardiac myocytes (FHCM) and a cell line derived from FHCM, termed W1, constitutively express low levels of MHC class I antigens and significant levels of ICAM-1 (CD54), and LFA-3 (CD58) but do not express LFA-1 alpha (CD11a), LFA-1 beta (CD18), GMP-140 (CD62), BB1-B7, VCAM-1, and ELAM-1. In vitro incubation of FHCM or the W-1 cell line for varying periods with varying concentrations of IFN-gamma, TNF-alpha, Poly IC, LPS, IL-alpha, IL-1 beta, PMA, PDBu, and supernatant fluids from Con A-activated PBMC or allogeneic MLR cultures failed to induce cell adhesion molecules (CAMs) or costimulatory molecules that are not constitutively expressed on these cells except for MHC class II antigens. In addition, IFN-gamma, Con A, and MLR supernatant fluids (in order of biological activity) not only induced MHC class II antigens but also markedly increased the mean density of expression per cell of MHC class I and ICAM-1. Analysis of the stability of MHC class I/II molecules using agents like brefeldin-A and Western blot analysis of MHC class II molecules suggest that these ligands are very stably expressed on myocytes. Our previous studies have documented the failure of MHC-expressing FHCM to induce an alloproliferative response. The results of the present studies show that this failure is not secondary to the absence of ICAM-1 or LFA-3 or the presence of unstable MHC molecules but is most likely due to the absence of other CAMs/costimulatory molecules that are critically required for inducing allogeneic activation.

Cell Adhesion Molecules↗
PubMed1994

Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and cardiac myosin-induced autoimmune myocarditis.

When mice of certain strains are infected with the cardiotropic virus coxsackievirus B3 or are immunized with mouse cardiac myosin, myocarditis, accompanied by immune recognition of the myocardium, ensues. That both target organ injury and peripheral immunization lead to similar disease manifestations raise questions about the role of tissue damage in eliciting autoantibodies. A/J mice were infected with coxsackievirus B3 or immunized with mouse cardiac myosin and killed at weekly intervals for 4 wk. A portion of each heart was examined histologically for evidence of myocarditis and antibodies were eluted from the remaining heart tissue. Heart eluates and serum were tested for IgG antibodies to myosin and to adenine nucleotide translocator and branched chain ketoacid dehydrogenase molecules by ELISA. At each sampling time, coxsackievirus B3-infected mice exhibited high titers of circulating antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase with successively increasing myocardial deposition of antibodies of each specificity. Among myosin-immunized mice, antibodies of all three specificities were eluted from the myocardium and were found in the serum, but only antibodies to myosin were present in appreciable amounts in the circulation. Antibodies to myosin, adenine nucleotide translocator, and branched chain ketoacid dehydrogenase were rarely observed in serum and heart eluates from control animals. This study indicates that myocardial injury may be a prerequisite for the induction of cardiac autoimmunity and suggests that as tissue damage accrues, recognition of additional cardiac Ag may occur.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1994

Inhibition of neutrophil adhesion during cardiopulmonary bypass.

Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB) causes a diffuse inflammatory reaction that includes neutrophil activation. The purpose of this study was to determine if inhibition of neutrophil adhesion with a new antiinflammatory agent NPC 15669 (N-(9H-(2,7-dimethylfluorenyl-9-methoxy)-carbonyl)-L-leucine) could reduce pulmonary injury in a porcine model of CPB. NPC 15669 blocks adherence of activated neutrophils by inhibiting upregulation of the Mac-1 (CD11b/CD18) adhesion molecule. Sixteen piglets underwent 2 hours of hypothermic CPB followed by 2 hours of observation; 8 received NPC 15669 (10 mg/kg intravenous bolus followed by 6 mg.kg-1.h-1 intravenous infusion) and 8 received equal volumes of vehicle. After 90 minutes of CPB, expression of neutrophil adhesion molecule subunit CD18 increased 118% in control piglets but only 36% in piglets treated with NPC 15669 (p < 0.01). Although neutropenia developed in all animals during CPB, lung tissue myeloperoxidase content was significantly lower in treated than in control animals 2 hours after CPB (94.9 +/- 10.4 versus 46.9 +/- 5.5 mumol.10 mg-1.min-1; p < 0.002). Free radical-mediated lipid peroxidation (quantitated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by treatment with NPC 15669 during and after CPB. Pulmonary function was better in NPC 15669-treated animals: 2 hours after CPB, pulmonary vascular resistance increased 477% in control piglets but only 140% in piglets receiving NPC 15669 (p < 0.03); arterial oxygen tension was significantly greater in piglets receiving NPC 15669 (428 +/- 33 mm Hg) than in controls (141 +/- 46; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Complement and neutrophil activation during cardiopulmonary bypass: a study in the complement-deficient dog.

Cardiopulmonary bypass (CPB) is known to cause complement and neutrophil activation, but the relative importance and interaction of these components in CPB-induced inflammation is unknown. In this study, a strain of dogs genetically deficient in the third component of complement (C3) was used to determine the contribution of C3 to neutrophil activation and pulmonary injury after CPB. Eleven dogs (5 C3-deficient and 6 controls) underwent 150 minutes of hypothermic CPB (28 degrees C) followed by 2 hours of observation. Before CPB, C3 levels were normal in controls and less than 1% of normal in C3-deficient dogs. In control dogs, functional activity of C3 decreased to 53.2% of baseline after 1 hour of CPB and there was immunohistochemical evidence of C3 deposition in lung after CPB; C3-deficient dogs had no C3 deposition in lung. Although similar degrees of neutropenia occurred during CPB in the two groups, expression of neutrophil adhesion molecule subunit CD18 was significantly lower in C3-deficient dogs than controls after 1 hour of CPB (45.9 +/- 3.7 versus 82.9 +/- 10.0 mean fluorescence units; p < 0.02). Postbypass lung tissue myeloperoxidase content was also less in C3-deficient dogs (43.8 +/- 4.6 versus 71.1 +/- 8.6 mumol x 10 mg-1 x min-1; p < 0.03). Cardiopulmonary bypass-associated lung injury (assessed by alveolar-arterial oxygen gradient, pulmonary vascular resistance, percent lung water, and light and electron microscopic appearance) was similar between groups. These results demonstrate that (1) C3 is deposited on pulmonary vascular endothelium during CPB and (2) C3 mediates increased expression of neutrophil CD18 and neutrophil sequestration in lung after CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hemodynamic vascular forces contribute to impaired endothelium-dependent vasodilation in reperfused canine epicardial coronary arteries.

OBJECTIVES: We studied canine coronary arterial vasoreactivity after occlusion and reperfusion to examine whether reduced flow or pressure contributed to the abnormalities observed. BACKGROUND: Ischemia and reperfusion alter endothelial and myocardial function. Causative factors may include altered flow, complement activation or free radical production by endothelial or white blood cells after reoxygenation and neutrophil activation. METHODS: The coronary arteries of anesthetized, open chest dogs were subjected to 90-min occlusion +/- 2 h of reperfusion. The effect of reperfusion on arterial responses to intracoronary acetylcholine, nitroprusside and phenylephrine was studied using in vivo ultrasound. Arterial segments were also harvested, perfused ex vivo with cell-free buffer and exposed to potassium chloride, nitroprusside, acetylcholine and bradykinin. The effect of ex vivo flow cessation with or without maintained intralumen pressure was also studied. RESULTS: Results are expressed as mean value +/- SEM. In vivo arterial cross-sectional area increased during infusion with acetylcholine (10(-5) mol/liter [18.5 +/- 9%]) and nitroprusside (10(-5) mol/liter [22.5 +/- 10%]) and decreased with phenylephrine (10(-5) mol/liter [7.6 +/- 7%]). After reperfusion, acetylcholine caused 13.5 +/- 9% vasoconstriction. Nitroprusside and phenylephrine responses were unchanged. Reperfused arterial segments also showed impaired vasodilation in response to 10(-6) mol/liter of acetylcholine (10.6 +/- 5.1% vs. 47.1 +/- 4.9% in control vessels) and 10(-8) mol/liter of bradykinin (4.4 +/- 6.7% vs. 27.9 +/- 8% in control vessels). Ex vivo flow cessation impaired acetylcholine-mediated vasodilation, but this abnormality was prevented when high intralumen pressure was maintained during the no-flow period. CONCLUSIONS: Reduction in flow and intralumen pressure contribute to the impaired acetylcholine-mediated vasodilation seen after coronary occlusion. This is prevented by maintaining high intralumen pressure during the no-flow period, suggesting that hemodynamic forces may change endothelial function independent of circulating complement or blood cell elements.

Acetylcholine↗
PubMed1994

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.

AIDS-Related Opportunistic Infections↗
PubMed1994

Circulating heart autoantibodies in familial as compared with nonfamilial idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (DCM) is a serious heart disease characterized by enlargement of one or both ventricles and ventricular dysfunction. Although most patients have sporadic disease, 20% have been found to have familial DCM when relatives are investigated by echocardiography. No other factors have been identified to date that consistently distinguish familial from nonfamilial DCM. Although some patients have a family history of DCM, a "negative" family history does not exclude familial DCM because affected family members may be presymptomatic or undiagnosed. Because some patients have life-threatening complications at the time of initial assessment of DCM, identifying a serum marker predictive of familial disease would help determine which families would most likely benefit from echocardiographic investigation. OBJECTIVE: In this study, our objective was to determine whether antiheart autoantibodies could be used to distinguish familial from nonfamilial idiopathic DCM. METHODS: We analyzed serum specimens for antiheart antibodies from 19 patients categorized as having familial DCM and 15 classified as having nonfamilial DCM on the basis of echocardiographic investigation of first-degree relatives. The mean duration of disease in these 34 patients was 50 months at the time the serum specimens were obtained. RESULTS: Titers of antibodies against the adenine nucleotide translocator, branched-chain keto acid dehydrogenase, and cardiac myosin did not distinguish between familial and nonfamilial cases of DCM.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1994

Inhibition of platelet adhesion during cardiopulmonary bypass reduces postoperative bleeding.

BACKGROUND: Thrombocytopenia and impaired platelet function after cardiopulmonary bypass (CPB) contribute to postoperative bleeding and may increase blood transfusion requirements. We tested the hypothesis that reversible inhibition of glycoprotein IIb/IIIa integrin-mediated platelet adhesion would reduce postoperative bleeding after CPB. METHODS AND RESULTS: Twelve mongrel dogs (21 to 24 kg) underwent 2.5 hours of hypothermic CPB followed by 6 hours of observation. The study group (n = 6) received a 90-micrograms/kg IV bolus of the glycoprotein IIb/IIIa inhibitor Integrelin, followed by continuous infusion (2 micrograms/kg per minute) during CPB; the control group (n = 6) received only drug vehicle. Platelet number and aggregometry, PaO2, and chest tube output were assessed serially. Lung wet weight, histology, and myeloperoxidase activity were also measured. At 120 minutes after CPB, the control group had significantly lower platelet counts (expressed as percent of pre-CPB values) when compared with the Integrelin group (control, 35.2 +/- 4.6%; Integrelin, 68.2 +/- 4.9%; mean +/- SEM; P < .05). Three hundred sixty minutes after CPB, platelet function (expressed as percent of pre-CPB aggregation induced by 10 mumol/L ADP) was better preserved in the Integrelin group (Integrelin, 20.8 +/- 3.0%; control, 43.9 +/- 10.4%; P < .05). The Integrelin group also had less total postoperative blood loss (control, 447 +/- 97 mL; Integrelin, 248 +/- 30 mL; P < .05). PaO2, lung wet weight, histology, and myeloperoxidase activity did not differ significantly between groups. CONCLUSIONS: This study demonstrates that inhibition of platelet adhesion during CPB results in (1) less platelet consumption, (2) better preservation of platelet function, and (3) less postoperative bleeding. Reversible platelet inhibition may have clinical utility in minimizing postoperative bleeding and reducing blood transfusions.

Animals↗
PubMed1994

Patterns of myocardial cell adhesion molecule expression in human endomyocardial biopsies after cardiac transplantation. Induced ICAM-1 and VCAM-1 related to implantation and rejection.

Conflicting patterns of myocardial cell adhesion molecule expression associated with cardiac rejection have emerged from numerous studies of randomly selected cardiac biopsies. We designed a prospective, longitudinal study which reports both qualitative and quantitative levels of myocardial ICAM-1, VCAM-1, E-selectin, and P-selectin expression in sequential human cardiac allograft biopsies. Intense ICAM-1 and VCAM-1 staining was found in all biopsies during the first three weeks after transplant and coincided with elevated serum levels of troponin T, a sensitive marker of ischemic myocyte injury. Baseline ICAM-1 and VCAM-1 expression returned within three to four weeks, as did serum troponin T levels in all patients who did not develop rejection. All 29 rejection episodes encountered were associated with intense ICAM-1 staining, while 24 of the 29 (83%) had intense VCAM-1 staining. Increased ELAM-1 and CD62 staining was only rarely observed. Persistence of increased ICAM-1 and VCAM-1 staining after treated rejection episodes predicted a recurrent rejection episode within two months (75% positive and 100% negative predictive value). Objective quantitative measurements by radioimmunoassay (RIA) confirmed these patterns of induced ICAM-1 and VCAM-1 expression. Thus, longitudinal monitoring of serial biopsies for myocardial ICAM-1 and VCAM-1 expression could be useful in the early detection of rejection episodes and monitoring the efficacy of immunosuppressive therapy.

Adult↗
PubMed1993

Role of IL-1 and tumor necrosis factor in coxsackie virus-induced autoimmune myocarditis.

We have previously reported that B10.A (H-2a) mice, which are resistant to the induction of postcoxsackievirus autoimmune myocarditis, become susceptible upon treatment with LPS, IL-1, or TNF. In this study, we show that the development of autoimmune myocarditis is associated with infiltration of the heart by inflammatory cells that secrete the cytokines IL-1 and TNF. Local secretion of these cytokines contributes to increased levels of IL-1 and TNF in the serum. Thus, local production of cytokines promotes the induction of this postinfectious autoimmune disease.

Animals↗
PubMed1993

Prevalence and incidence of left ventricular dysfunction in patients with human immunodeficiency virus infection.

The prevalence and incidence of left ventricular (LV) dysfunction was examined in patients infected with the human immunodeficiency virus (HIV). Sixty-nine randomly selected patients diagnosed with HIV infection who were followed in HIV clinics were prospectively evaluated by 2-dimensional echocardiography. Mean follow-up duration was 11 months. Additionally, 39 consecutive HIV-infected patients referred to the Cardiomyopathy Service and found to have LV dysfunction by 2-dimensional echocardiography were also studied. Of the 39 referred patients, 34 (87%) were referred for recent onset, unexplained, congestive heart failure. During this time, the HIV clinic population comprised 1,819 alive and actively followed patients; the 39 cardiomyopathy referrals therefore constituted a crude rate of 2.1% for this population. Of the 69 prospectively studied patients without clinical heart disease, a 14.5% prevalence of global LV hypokinesia and an incidence of 18%/patient-year were found. During a maximal 18-month follow-up period, 4 prospective patients (5.8%) developed symptoms of congestive heart failure. A greater proportion of prospective and referred patients with LV dysfunction had CD4 counts < 100/mm3 (62 and 79%, respectively) than did that of those without LV dysfunction (35%). In conclusion, the high rate of unexpected LV dysfunction in this HIV-infected population suggests that early cardiac contractile abnormalities may involve a significant number of patients, most of whom have low CD4 counts. A subgroup of these patients appears to progress to symptomatic congestive heart failure.

Adult↗
PubMed1993

Demographic features and prevalence of idiopathic myocarditis in patients undergoing endomyocardial biopsy.

From January 1985 through December 1990, 534 patients underwent endomyocardial biopsy at Johns Hopkins Hospital for suspected myocarditis. One hundred thirty-eight (26%) biopsy specimens were diagnosed histologically by 2 cardiac pathologists as either active (n = 85, 16%) or borderline (n = 53, 10%) myocarditis. Of the 138 patients, 60 were excluded based on either specific concurrent clinical conditions or noncongestive heart failure presentations. Immunohistochemical staining for common leukocyte antigen infiltrating cells performed on the remaining 78 specimens confirmed the presence of focal or multifocal inflammatory infiltrates in 58, of which 49 had histologic evidence of active myocarditis. All 49 patients presented with congestive heart failure and left ventricular ejection fractions of < 40%. Compared with patients with either idiopathic dilated cardiomyopathy (n = 207) or ischemic cardiomyopathy (n = 44), these patients with myocarditis had a less striking male predominance (58 vs 69 and 83%, respectively) (p = 0.02) and were younger (43 +/- 16 vs 50 +/- 17 and 55 +/- 13 years, respectively, p = 0.005). Racial distributions were similar. A recent history of a discrete flu-like illness was obtained in 52%, two-thirds of which were clustered between the months of December and March. Onset of heart failure peaked between December and April (63% and was low between May through September (22%). A peak in the proportion of patients found to have active myocarditis on biopsy occurred in 1986 (17 vs 7 to 10% in other years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗