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Biomedical subjects

J Narula

Publications and source records attributed to J Narula.

At least 73 records · Page 4Linked to original sources
PubMed1996

Echocardiographic evaluation of patients with acute rheumatic fever and rheumatic carditis.

BACKGROUND: Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis. METHODS AND RESULTS: Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%. CONCLUSIONS: In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.

Acute Disease↗
PubMed1996

Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium.

Biodistribution and infarct accumulation of different liposome preparations in rabbits with experimental myocardial infarction have been investigated. The influence of such parameters as liposome size, and presence or absence of poly(ethylene glycol) (PEG) and infarct-specific antimyosin antibody (AM) on liposome behavior in vivo was studied. All three variables were shown to affect liposome biodistribution, liposome size being the least significant variable. Statistical analysis of the data obtained demonstrated that of all variables, PEG coating expresses the strongest influence on the liposome blood clearance, significantly (P=0.0001) increasing the mean level of blood radioactivity under all circumstances. Infarct accumulation depended upon the presence of both PEG (P=0.0013) and AM (P=0.005). The infarct-to-normal ratio was affected by the presence of AM (P=0.0002), but the extent of the effect depended also on the presence of PEG (P=0.01). Two differing mechanisms can be seen in infarct accumulation of PEG-liposomes (slow accumulation via the impaired filtration) and AM-liposomes (specific binding of immunoliposomes with the exposed antigen). Both mechanisms are supplementary in case of liposomes carrying PEG and AM at the same time. An optimization strategy is suggested for using liposomes as carriers for diagnostic (a high target-to-nontarget ratio is required) and therapeutic (a high absolute accumulation in the target is required) agents.

Animals↗
PubMed1996

Protective effect of butylated hydroxyanisole on adriamycin-induced cardiotoxicity.

Adriamycin has a wide spectrum of antitumour activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from the generation of oxygen free radicals. The objective of the present study was to investigate the influence of the antioxidant, butylated hydroxyanisole co-therapy on the cardiotoxicity of adriamycin, in-vivo. The aqueous solubility of butylated hydroxyanisole was enhanced by inclusion complex formation with hydroxypropyl-beta-cyclodextrin. The extent of drug-induced myocardial damage in rats was assessed using intravenous 111In-labelled antimyosin Fab and chronological changes in serum creatine kinase levels. There was a dose-related increase in myocardial antimyosin uptake in rats, which reached a plateau at an adriamycin dose of 10 mg kg-1. The antimyosin uptake at this dose (% dose g-1 = 0.1942 +/- 0.0150, n = 8) was significantly reduced by co-administration of butylated hydroxyanisole with adriamycin (10 mg kg-1 of each) to 0.1462 +/- 0.0116 (n = 5, P < 0.05). Assessment of cardiotoxicity in the rats was also performed by measuring serial changes in serum creatine kinase levels. Increasing doses of adriamycin caused an increase in serum creatine kinase levels with peak values obtained between 2 and 8 h after dosing. These values decreased upon co-administration of butylated hydroxyanisole with adriamycin at 10 mg kg-1, each and 30 mg kg-1 each by 29 and 41%, respectively. On the other hand, butylated hydroxyanisole did not inhibit the tumouricidal activity of adriamycin as investigated in-vitro using the NMU rat mammary adenocarcinoma cell-line. The significant reduction in anthracycline cardiotoxicity by butylated hydroxyanisole coadministration may result from its scavenging action on adriamycin-mediated free-radical formation or its enhancement of activity of enzymes involved in the metabolism of adriamycin.

Animals↗
PubMed1996

Acute pancreatitis due to zinc phosphide ingestion.

The case of a young woman is described who suffered from acute pancreatitis related to the ingestion of zinc phosphide. This unusual complication was successfully managed with conservative treatment.

Acute Disease↗
PubMed1995

Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments.

BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.

Animals↗
PubMed1995

Plug and seal: prevention of hypoxic cardiocyte death by sealing membrane lesions with antimyosin-liposomes.

The hallmark of cell death is the development of cell membrane lesions. Such lesions in the myocardium are usually associated with acute myocardial infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy constitutes the only major treatment to date. We envisioned a method to seal these membrane lesions using immunoliposomes as a novel adjunctive approach. An antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is used as an anchoring site, and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are cardiocytes and are propagated in tissue culture and their viability may be assessed by various methods. Viability assessed by [3H]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue exclusion and by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by targeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological systems.

Animals↗
PubMed1995

Non-invasive detection of myocyte necrosis in myocarditis and dilated cardiomyopathy with radiolabelled antimyosin.

The 'gold standard' for the diagnosis of myocarditis is endomyocardial biopsy. Although the specificity of this invasive method is good, its sensitivity is questionable. Therefore, a non-invasive diagnostic method with greater sensitivity (even if it were overly sensitive) would constitute a useful screening tool for identification of patients who should undergo endomyocardial biopsy. Antimyosin immunoscintigraphy fits such a criterion since it is highly sensitive and specific for diagnosis of myocardial necrosis, which is one of the two obligatory components for the diagnosis of myocarditis. Therefore studies were performed on patients with clinical histories suggestive of myocarditis such as acute onset of dilated cardiomyopathy, myocarditis masquerading as acute myocardial infarction and patients presenting with unexplained life-threatening ventricular tachyarrhythmias. In all these studies, antimyosin imaging had higher sensitivity than endomyocardial biopsy for the diagnosis of myocarditis. A rationale is provided for the increased sensitivity and specificity of antimyosin immunoscintigraphy for diagnosis of myocyte necrosis associated with myocarditis, relative to endomyocardial biopsy.

Autoantibodies↗
PubMed1995

SR-Ca2+ ATPase as an autoimmunogen in experimental myocarditis.

The concept of autoimmunity in the pathogenesis of myocarditis or dilated cardiomyopathy is gaining impetus. Since systolic functional impairment and subsequent recovery are frequently observed in myocarditis, we reasoned that the development of autoimmunity to cardiac sarcoplasmic reticulum calcium ATPase (SR-Ca2+ ATPase), which could interfere with intracellular calcium regulation and therefore affect myocardial contractility, should lead to immune-mediated myocarditis in experimental animals. Murine monoclonal antibody 4C11-20.21 (IgM class) generated against canine cardiac SR-Ca2+ ATPase inhibits the cardiac but not the skeletal ATPase activity. Immunization of CAF1/J mice with 4C11-20.21-affinity-column-purified cardiac SR-ATPase produced a time-dependent induction of myocardial injury consistent with the diagnosis of myocarditis. Furthermore, the antibody 4C11-20.21 alone can induce myo-necrosis in severe combined immunodeficiency (SCID) mice indicating a mechanism of cardiomyopathy independent of the cytotoxic T-cell mediated autoimmunopathy. Administration of 4C11-20.21 into immunocompetent CAF1/J mice resulted in minimal myocardial abnormality (40% with perivascular and/or interstitial mononuclear lymphoplasmacytoid aggregates, 10% with borderline myocarditis and 10% with lesions consistent with focal myocarditis). All control animals had normal hearts. Immunoperoxidase electron microscopic examination of the involved cardiac tissues showed antibody localization in the subsarcolemmal myotubular system and focal staining of the immediately adjacent sarcolemma in mice injected with 4C11-20.21 but not with 2C12.1B5. The time-dependent association between cardiac SR-Ca2+ ATPase administration and development of myocardial lesions, as well as potentiated induction of myonecrosis with anti-cardiac SR-Ca2+ ATPase antibody in SCID relative to immunocompetent mice, suggest a potential autoimmunopathogenic role of cardiac SR-Ca2+ ATPase in experimental myocarditis.

Animals↗
PubMed1994

Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody.

CD44 is a M(r) 90,000 surface glycoprotein believed to be involved in cell adhesion and migration. We investigated the role of CD44 in tumor growth and metastasis using human melanoma cell lines SMMU-1 and SMMU-2. Both SMMU-1 and SMMU-2 form tumors in the s.c. tissues when injected s.c. in SCID mice but only SMMU-2 metastasizes. Approximately one-half of SCID mice receiving injections of SMMU-2 s.c. develop metastatic tumors. SMMU-2 but not SMMU-1 expresses high levels of the hematopoietic form of CD44 and binds fluorescence-conjugated hyaluronic acid in vitro. GKW.A2 is a monoclonal antibody specific for human CD44 that can completely inhibit the binding of hyaluronic acid to SMMU-2 tumor cells in vitro. Moreover, in vivo injection of GKW.A3 inhibited the growth and metastatic potential of SMMU-2 tumor cells. Administration of GKW.A3 i.v. 1 week after s.c. tumor injection did not inhibit local tumor development but inhibited the formation of metastatic tumors and prolonged animal survival. Therefore, interactions between CD44 on tumor cells and its ligands in vivo may be necessary for tumor growth and metastasis.

Animals↗
PubMed1994

Incidence of rheumatic fever and prevalence of rheumatic heart disease in India.

Rheumatic heart disease (RHD) has been documented in Indian medical literature since the early nineteenth century, contrary to the popular belief that rheumatic fever (RF) and its sequelae were exclusively prevalent in temperate climates until the early twentieth century. Rheumatic heart disease has, in the past 50 years, emerged as a major contributor to cardiovascular morbidity in India. Despite the paucity of clear information regarding secular trends, the few available community surveys indicate that there are at present more than 1 million patients with RHD. Even a conservative estimate of the incidence of RF suggests that at least 50,000 new episodes occur every year. The younger age of onset (juvenile RHD) seen in India is a special feature of both public health and clinical importance. These patterns of RF and RHD, which may be similar to those in other developing countries, underscore the importance of effective public health strategies for prevention and control.

Adolescent↗
PubMed1994

Cardiac sarcoplasmic reticulum calcium ATPase, an autoimmune antigen in experimental cardiomyopathy.

BACKGROUND: Various myocardial cell surface and intracellular antigens have been associated with autoimmune myocarditis. Since sarcoplasmic calcium overload is a recognized pathobiochemical finding in cardiomyopathy, we reasoned that there might be a causal relation between inhibition of sarcoplasmic calcium exclusion and pathogenesis of the disease and that immunization with sarcoplasmic reticulum calcium ATPase (SR-ATPase) or antibody specific for SR-ATPase, which can interfere with the regulation of the intracellular calcium content and the myocardial contractility, should lead to the development of cardiomyopathy and possibly myocarditis. METHODS AND RESULTS: Monoclonal antibody 4C11-20.21 (IgM class) specific for canine cardiac SR-ATPase (M(r) approximately 110 kD) was generated by immunization of CAF1/J mice with dog heart sarcoplasmic reticulum. Antibody 4C11-20.21 inhibits 75% of the enzymatic activity of the cardiac SR-ATPase. This antibody also cross-reacts with the higher M(r) subunit of canine skeletal SR-ATPase, but the skeletal muscle SR-ATPase activity is unaffected. This antibody does not cross-react with sarcolemmal calcium ATPase (134 kD). Antibody 4C11-20.21 was used for affinity purification of cardiac muscle SR-ATPase, which did not contain sarcolemmal calcium ATPase antigen. Nine of 11 CAF1/J mice injected with purified canine cardiac SR-ATPase protein demonstrated myocardial lesions: 3 of 4 mice had occasional perivascular and/or interstitial mononuclear cell infiltrates after 3 weeks, 3 of 4 had borderline myocarditis after 6 weeks, and 3 of 3 had focal myocarditis after 12 weeks. No mononuclear infiltrates were seen in any other organ. To identify the independent effect of 4C11-20.21 antibody on cardiac muscle, 2 x 10(6) hybridoma cells producing the antibody were injected intraperitoneally into 12 severe combined immunodeficiency (SCID) mice. Eleven of 12 SCID mice showed variable cardiac myocyte degeneration without cellular infiltration between 8 and 19 days. Three control SCID mice, which received equivalent injections of hybridoma cells producing IgM anti-myosin light chain antibody, did not show any pathological lesions. Immunoperoxidase staining and/or immunoperoxidase transmission electron microscopy for detection of in vivo localization of 4C11-20.21 demonstrated staining of the subsarcolemmal myotubular system and focal staining of immediately adjacent sarcolemma in animals that received either 4C11-20.21 hybridoma cells or purified canine cardiac SR-ATPase antigen but not in controls. Immunofluorescence staining with goat anti-mouse C3 antibody revealed focal deposition of complement in the cardiac myocytes. CONCLUSIONS: The time-dependent association between immunization with SR-ATPase antigen and the development of myocarditis in mice suggests that cardiac SR-ATPase constitutes one of several autoimmunogens capable of inducing autoimmune myocarditis. Besides antigenic specificity, since antibody to cardiac SR-ATPase also inhibits energy-dependent processes in the myocardium, it is reasonable to associate the pathological evidence of myonecrosis with the interference of calcium regulation, which controls myocardial contractility.

Animals↗
PubMed1994

Evaluation of myocardial infarct size before and after reperfusion: dual-tracer imaging with radiolabeled antimyosin antibody.

UNLABELLED: Antimyosin antibody is a specific marker of myocardial necrosis that is based on the loss of integrity of the sarcolemmal membrane. Because antimyosin can be labeled with several different radiotracers, gamma imaging performed with antimyosin labeled with two different radionuclides can be used to quantify infarct size before and after an intervention such as reperfusion. METHODS: Twelve open-chested anesthetized dogs were evaluated both at the end of 1.5 hr of occlusion of the left anterior descending coronary artery and following reperfusion. Antimyosin Fab radiolabeled with either 123I or 111In was injected by intracoronary administration over 3 min at the end of the occlusion interval, and the coronary sinus was drained continuously for 7 min to prevent recirculation of the antibody. One hour after reperfusion, a second injection of antimyosin Fab (labeled with a different isotope from the first) was administered as before. Six dogs were given intracoronary trifluoperazine (150 micrograms/kg of body weight) simultaneously with reperfusion, and another six dogs received saline as the control. The infarct size in grams before and after reperfusion was assessed by antimyosin antibody uptake in ex vivo images of 1-cm thick slices of the hearts. The mean infarct sizes before (W1) and after (W2) reperfusion were then calculated as the percent of infarcted myocardium/ventricular myocardial mass. RESULTS: There was a significant increase in the mean percent infarct size after reperfusion in the control group (W2 = 16.73 +/- 4.0, W1 = 14.92 +/- 3.88; p = 0.029). The mean infarct size was uniformly smaller with trifluoperazine intervention (W2 = 12.33 +/- 2.03, W1 = 16.34 +/- 2.78; p = 0.004). The difference between the mean change in the infarct sizes in the two groups was highly significant (p = 0.002). CONCLUSION: Dual imaging of the extent of myocardial necrosis before and after an intervention (reperfusion) in the same animal demonstrated the utility of antimyosin imaging to document changes in the extent of necrosis.

Animals↗
PubMed1993

Cardiac compression with mitral stenosis: a haemodynamic challenge.

The hemodynamics of pericardial restriction (diastolic equilibration of pressures in all the four chambers of heart) and that of mitral stenosis (presence of an end diastolic gradient between the left atrium and the left ventricle) appear mutually exclusive. We describe herein hemodynamic findings in two patients of rheumatic mitral stenosis associated with pericardial constriction in one patient and pericardial effusion with tamponade in the other. Disproportionate elevation of the pulmonary artery diastolic and wedge pressures as compared to the right atrial mean, and left and right ventricular end diastolic pressures was present in both patients. In constrictive pericarditis, the respiratory variation in pressure was reflected in the pulmonary artery wedge pressure but not in the left ventricular end diastolic pressure. The gradient between the pulmonary artery wedge pressure and the left ventricular end diastolic pressure was abolished completely during the inspiratory phase of respiration despite significant mitral stenosis. The difference in the pressure, however, was maintained throughout inspiration and expiration in pericardial effusion with tamponade. In patients with constrictive pericarditis and mitral stenosis, the pulmonary artery wedge pressure does not appear to be a true indicator of the left atrial pressure.

Adult↗
PubMed1993

Does endomyocardial biopsy aid in the diagnosis of active rheumatic carditis?

BACKGROUND: Carditis is the only component of rheumatic fever that leads to permanent disability. The diagnosis of carditis is presently made by using composite clinical criteria based on the revised Jones' criteria. Since myocardial involvement is an important component of rheumatic carditis, right ventricular endomyocardial biopsies were performed in 54 patients with clinical acute rheumatic fever and quiescent rheumatic heart disease to evaluate the role of biopsy for the diagnosis of rheumatic carditis. METHODS AND RESULTS: In 11 of the 54 patients, clinical consensus was certain about rheumatic fever and carditis based on the revised Jones' criteria (group 1). Histomorphological abnormalities in these patients were scarce. The diagnostic features of rheumatic myocarditis including Aschoff nodules or histiocytic aggregates were encountered in 3 patients (27%). Lymphocytic infiltration was sparse. A majority of patients demonstrated myocyte degeneration, interstitial degeneration, or occasional interstitial mononuclear cell infiltration, but since these histopathological lesions may occur in other conditions also, they were considered nondiagnostic. In 33 of the 54 patients with preexisting rheumatic heart disease, the diagnosis of carditis was suspected based on varied clinical presentations. Since previous cardiac findings were not available in these patients, the clinical diagnosis of carditis could not be made without equivocation (group 2). Twenty-three patients presented with unexplained acute onset of congestive heart failure and evidence of recent streptococcal infection (group 2A). While 13 of them had one or more other major manifestations, 10 patients had only minor manifestations. Mimetic carditis was suspected in the remaining 10 of 33 patients based on carditis having occurred in previous episodes of rheumatic fever (group 2B). The endomyocardial biopsy provided confirmatory evidence of rheumatic myocarditis in 9 patients of group 2A but in none of the 10 patients with suspected mimetic carditis. Nondiagnostic myocyte or interstitial alterations were frequently observed in group 2. Ten of the 54 patients had no clinical evidence of active carditis (group 3). No histological alterations diagnostic of rheumatic carditis were noted in these patients. Twenty-two follow-up biopsies were performed in the first 10 consecutive patients. Diagnostic histiocytic aggregates or Aschoff nodules were observed in initial biopsies in 4 of 10 patients, and nonspecific myocyte or interstitial alterations were observed in 9. All patients with diagnostic changes in initial biopsy demonstrated fibrohistiocytic nodules in 6- or 12-week biopsy samples. Nondiagnostic alterations, similar to those seen in acute cases, were present in 5 of 8 patients at 6 weeks, 5 of 8 patients at 12 weeks, and 3 of the 6 patients at 24 weeks despite the presumed adequate immunosuppressive therapy. No complications related to biopsy were encountered. CONCLUSIONS: The present study highlights the low frequency of diagnostic features in the biopsy specimens of patients with definite clinical rheumatic carditis. Although such alterations are not observed in patients with chronic rheumatic heart disease, endomyocardial biopsy does not appear to provide additional diagnostic information where clinical consensus is certain about diagnosis of rheumatic carditis. Our study, however, substantiates the concept of carditis underlying unexplained congestive heart failure of acute onset in patients with preexisting rheumatic heart disease and elevated antistreptolysin-O titers.

Acute Disease↗