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PubMed1993

Histopathologic evidence for cardiomyopathy in a child with mitral valve prolapse.

An intriguing relationship between idiopathic mitral valve prolapse (MVP) and cardiomyopathy has been reported in adult cases of MVP. This paper reports a girl with idiopathic MVP, who presented with progressive cardiomegaly and cardiomyopathic findings or, cardiac biopsy; right ventricular endomyocardial biopsy at the age of 15 years showed myocardial hypertrophy, disarray, myocardial degeneration, interstitial fibrosis and endocardial thickening. To our knowledge, this is the first case of idiopathic MVP in childhood that has been shown to have positive biopsy findings for cardiomyopathy.

Biopsy↗
PubMedDate not supplied

Eosinophilic explant carditis with eosinophilia: ?Hypersensitivity to dobutamine infusion.

BACKGROUND: Eosinophilic carditis with peripheral eosinophilia has been observed in a number of clinical situations. This report describes this association in patients undergoing heart transplantation and offers a possible explanation. METHODS: The clinical records and explanted hearts of 31 consecutive patients who received primary orthotopic heart transplants were reviewed. Clinical features particularly analyzed included the following: age, cardiac status and assistance devices, catheterizations, medical or surgical disorders including parasites, tryptophane exposure, medications, and peripheral blood counts. Pathologic features particularly studied included the following: dilatation and hypertrophy, fibrosis, mural thrombi, carditis, eosinophils, myocardial necrosis, vasculitis, valvular disease, and coronary artery disease. Prior endomyocardial biopsy specimens were also reviewed. RESULTS: Seven patients had eosinophilic carditis compatible with hypersensitivity carditis. Eight had eosinophilia. All patients with carditis received intravenous dobutamine (Dobutrex solution) continuously for more than 1 month immediately preceding transplantation. All patients with eosinophilia received intravenous dobutamine continuously for 15 days or longer and exhibited eosinophilia only during dobutamine therapy with the exception of one patient in whom eosinophilia was observed 8 days after cessation of 8 days of therapy. Among 13 patients who received dobutamine for more than a month immediately before transplantation, nine had eosinophilic carditis, peripheral eosinophilia, or both. CONCLUSIONS: Prolonged continuous intravenous administration of dobutamine was associated with eosinophilic carditis and eosinophilia. No other clinical factor with a relationship to either eosinophilia or carditis was identified. The responsible agent may have been a preservative in the dobutamine solution, sodium bisulfite.

Adult↗
PubMed1993

New approach to the estimation of the extent of myocardial fibrosis in patients with dilated cardiomyopathy: use of signal-averaged electrocardiography.

To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filtered QRS complex (fQRSd) and the duration of low amplitude signals < 40 microV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd (r = 0.623, p < 0.001), LAS (r = 0.570, p < 0.001), and V40 (r = -0.355, p < 0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd (r = 0.695, p < 0.0001), LAS (r = 0.640, p < 0.0001), and V40 (r = -0.533, p < 0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy.

Adult↗
PubMed1990

Collagen profile in the transplanted heart.

To substantiate the finding of interstitial myocardial fibrosis in the transplanted heart and to characterize the collagen profile of the transplanted heart, we studied endomyocardial biopsy specimens from 30 heart transplants and four heart-lung transplants at 1 to 82 months after transplantation. Indirect immunofluorescent techniques with affinity-purified antibodies for collagen types I, III, IV, and V were used. The degree of interstitial collagen present was scored. The amount of type I collagen was increased in transplants from distant donors (mean ischemia time, 154 minutes) compared with those from on-site donors (mean ischemic time, 59 minutes): collagen scores 1.1 and 1.7, respectively (P less than .01). There was a trend toward a positive correlation, not statistically significant, between cyclosporine dose and collagen III deposition (r = .35), collagen IV (r = .38), and collagen V (r = .56). There was a negative correlation between number of rejection episodes and mean cyclosporine dose (r = -.41) and amount of collagen III (r = -.42) or collagen IV (r = -.42). No correlations were found between collagen deposition and any other variables studied. These results confirm the mixed nature of the collagen deposited and suggest that some fibrosis is related to cyclosporine administration rather than to the number of prior healed rejection episodes.

Adult↗
PubMed1992

[A case of brain stem encephalitis complicated with bifascicular block caused by rubella virus].

We reported a case of a 29-year-old man who had been in good health until contracting brain stem encephalitis due to a rubella virus 5 years previously, at which time the ECG revealed complete right bundle branch block and right axis deviation. An ECG obtained 6 months earlier had been within normal limits. Since yearly health checkups continued to show the same abnormalities, the patient was admitted for closer examination. At the time of admission, physical findings and blood tests revealed no abnormalities. No cardiomegaly nor pulmonary congestion was observed on chest X-rays either at the time of the original illness or at this time. An endomyocardial biopsy specimen obtained from the right ventricle revealed size variation of cardiac myocytes, moderate disarrangement, and mild myocardial interstitial fibrosis, indicative of post-myocarditic changes. The above findings suggest that bifascicular block (right bundle branch and posterior fascicle) appeared at the time of the rubella virus infection, in the pathogenesis of which the involvement of myocarditis was strongly suspected. Some patients developing myocarditis do not manifest cardiac symptoms such as heart failure. In these cases, conduction disturbances are the sole sequelae. To differentiate pathogenesis in such cases, endomyocardial biopsy was thought to be of value.

Adult↗
PubMed1993

Influence of collagen network on left ventricular systolic and diastolic function in aortic valve disease.

OBJECTIVES: The purpose of this study was to evaluate left ventricular structure-function interplay in aortic valve disease. BACKGROUND: An increase in myocardial fibrosis has been demonstrated in aortic valve disease, but changes in the collagen network and their effect on ventricular function have not been defined. METHODS: Left ventricular structure was assessed from left ventricular endomyocardial biopsy specimens obtained in 32 patients with aortic valve disease (aortic stenosis in 25, aortic regurgitation in 7). Total collagen volume fraction, orthogonal collagen fiber meshwork (cross-hatching), endocardial fibrosis, muscle fiber diameter and volume fraction of myofibrils were determined by morphologic-morphometric evaluation. Control biopsy data were obtained from six donor hearts before transplantation. Eleven other patients with normal left ventricular function served as hemodynamic status control subjects. Left ventricular biplane cineangiography and high fidelity pressure measurements were carried out in all patients. Systolic function was assessed from ejection fraction. Diastolic function was evaluated by the time constant of relaxation, early and late peak filling rates and the constant of passive myocardial stiffness. Patients were assigned to three groups according to increasing severity of nonmyocyte tissue alterations. Group 1 comprised 10 patients with elevated total collagen volume fraction. Group 2 comprised 6 patients with normal total collagen volume fraction and the presence of increased cross-hatching or endocardial fibrosis, or both. Group 3 comprised 16 patients with elevated total collagen volume fraction and the presence of cross-hatching or endocardial fibrosis, or both. RESULTS: Muscle fiber diameter was increased in the three groups with aortic valve disease, whereas the volume fraction of myofibrils was comparable in all four study groups. Ejection fraction was depressed in groups 2 and 3 compared with the control group. The time constant of relaxation was prolonged in the three groups with aortic valve disease. No differences in early and late peak filling rate were observed in the four study groups, but the constant of myocardial stiffness increased in groups 2 and 3. CONCLUSIONS: In aortic valve disease, changes in collagen architecture are associated with altered systolic function and passive diastolic properties. The sole increase in total collagen volume fraction without a change in architecture leaves systolic and passive diastolic function unaltered.

Adult↗
PubMed2005

Relation of myocardial histomorphometric features and left ventricular contractile reserve assessed by high-dose dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: This study was designed to determine the relationship between histomorphometric features and contractile reserve assessed by high-dose dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy. METHODS: Twenty-four consecutive patients (21 men, aged 43.4+/-8.7 years) with idiopathic dilated cardiomyopathy underwent dobutamine stress echocardiography. Wall motion score index, ejection fraction, cardiac power output and end-systolic pressure/volume ratio were used as indices of left ventricular contractility. Left ventricular endomyocardial biopsy specimens (3-5 per patient) were routinely processed and stained with Masson trichrome, interstitial fibrosis and myocyte diameter were calculated quantitatively. RESULTS: Myocyte diameter and interstitial fibrosis showed strongest correlation with change in wall motion score index (r=-0.667, p<0.001, and r=-0.567, p=0.004, respectively), followed by change in ejection fraction (r=-0.603, p=0.002, and r=-0.467, p=0.021, respectively). Interstitial fibrosis showed no correlation with change of cardiac power output and end-systolic pressure/volume ratio, whereas myocyte diameter was associated with change of both indices (r=-0.565, p=0.004, and r=-0.455, p=0.025). CONCLUSIONS: Contractile reserve elicited by high-dose dobutamine is strongly related to the degree of histological disruption in patients with idiopathic dilated cardiomyopathy.

Adult↗
PubMed2000

Life supporting function for over one month of a transgenic porcine heart in a baboon.

BACKGROUND: Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS: Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS: The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS: This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

Animals↗
PubMed1987

Cyclosporin-A induced heart failure after orthotopic heart transplantation.

Two patients suffering from dilated Cardiomyopathy (CMP) had to undergo orthotopic heart transplantation (HTX). In both cases, the postoperative period was without any complications. The immunosuppression consisted of Cyclosporin-A and Azathioprine including a one week prophylactic treatment with Antithymocyte Globuline (ATG). Four months postoperatively, they developed clinical signs of heart failure. The endomyocardial biopsies showed rejection at stage I according to Billingham's grading plus a fine interstitial fibrosis. Therefore, the Cyclosporin treatment was suspended and replaced by conventional immunosuppression consisting of Prednisolone and Azathioprine. Acute heart failure was managed by catecholamines in combination with aggressive diuretic therapy. After three weeks, both patients recovered. 12 weeks later, one died because of an acute rejection episode. The other is in good condition, with conventional immunosuppression at the present time. A vascular process caused by Cyclosporin-A as the pathogenic mechanism is considered. The absence of rejection signs in the biopsies as well as the remarkable improvement of heart failure after withdrawal of Cyclosporin-A support this possibility.

Coronary Disease↗
PubMed1998

Familial sick sinus syndrome with atrioventricular conduction disturbance.

A family with sick sinus syndrome is presented: a mother and her 2 daughters affected with sinus node dysfunction. Electrophysiological studies revealed abnormal atrioventricular conduction in the 2 daughters. All 3 individuals were implanted with a permanent pacemaker to relieve their symptoms. Endomyocardial biopsy from the right ventricle of one daughter showed disarrangement, degeneration, myocyte necrosis and interstitial fibrosis suggestive of myocardial disease.

Adult↗
PubMed1999

A case of peripartum eosinophilic myocarditis.

A 19-year-old postpartum patient with a previous history of asthma and eosinophilic myocarditis is described. Eosinophilic myocarditis is thought to be caused by exacerbation of the idiopathic hypereosinophilic syndrome by pregnancy. The diagnosis was made by a right ventricular endomyocardial biopsy, which showed an eosinophilic infiltrate with a few scattered foci of myonecrosis, but no fibrosis, vasculitis or granulomas. The patient's myocardial function continued to decline over a two-year follow-up period, despite normal levels of eosinophils. She developed echocardiographic evidence of diastolic and systolic dysfunction.

Adult↗
PubMed1988

Cardiomyopathies with particular reference to the diagnostic relevance of endomyocardial biopsies.

A distinction is made between heart muscle diseases with a known cause, or occurring as part of a systemic disease, and those of unknown cause. The first category is termed "specific heart muscle disease". The term "cardiomyopathy" is then limited to the latter category. Cardiomyopathies are categorized as dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy. The pathology of dilated cardiomyopathy depends on the clinical stage of the disease. Basically, the histology shows hypertrophic myocytes, often with degenerative signs, and interstitial fibrosis. Lymphocytes may be observed, particularly in cases studied shortly after the onset of symptoms. Endocardial thickening may occur in time. The role of endomyocardial biopsies in the clinical setting is limited and relates mainly to excluding other diseases, such as myocarditis. The pathology of hypertrophic cardiomyopathy is characterized by myocardial wall thickening, either asymmetric or symmetric, and disorganization of the normal myocardial texture. The latter phenomenon should be distinguished from disarray, since it may occur as a natural phenomenon. The differentiation between these two may be extremely difficult on the basis of only small tissue samples, as with endomyocardial biopsies. This, therefore, poses serious limitations in the use of endomyocardial biopsies. The pathology of restrictive cardiomyopathy also depends on the stage of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1996

Association of myotonic dystrophy and sick sinus syndrome, with special reference to electrophysiological and histological examinations.

Sick sinus syndrome is a rare but potentially important cardiac disorder in patients with myotonic dystrophy. We evaluated 3 patients with myotonic dystrophy complicated with sick sinus syndrome using intracardiac electrocardiography and endomyocardial biopsy. Electrocardiography identified sinus arrest, atrial flutter and right bundle-branch block in 2 cases and marked sinus bradycardia and first-degree atrioventricular block in 1 case. Their sinus node recovery times were significantly prolonged as demonstrated by the overdrive suppression test. Two patients had Adams-Stokes syndrome and one had tachycardia with severe palpitations. Therefore permanent pacemaker implantation was indicated in all 3 cases. Light microscopic analysis of right ventricular endomyocardial biopsies showed vacuolar degeneration and nuclear deformity of cardiomyocytes in all cases and endocardial and interstitial fibrosis in 1 case. These findings indicate that pathological changes may occur in any part of the myocardium in patients with myotonic dystrophy.

Adult↗
PubMed1999

[An elderly case of triple-vessel coronary artery disease with alternating bundle branch blocks in serial electrocardiograms].

An 82-year-old woman was admitted with severe chest pain and orthopnea on January 17, 1997. Physical examination revealed bilateral leg edema and cyanosis at the periphery of the extremities. The serum CK level was 488 IU/l on admission and increased to a maximum value of 4,866 IU/l 8 hours after admission. An echocardiogram demonstrated diffuse severe hypokinesis in the left ventricle. Serial electrocardiograms showed transient right bundle branch block, left bundle branch block, and normal sinus rhythm. The patient was diagnosed as having congestive heart failure. Artificial ventilation was performed, and furosemide, isosorbide dinitrate and dopamine were administered. A right ventricular endomyocardial biopsy performed on the 13th hospital day demonstrated moderate hypertrophy and disparity of cardiac myocytes and fibrosis around the myocytes, and few inflammatory cells in the specimens. This biopsy finding was not compatible with acute myocarditis but with the chronic stage of myocarditis. The patient was discharged on the 45th hospital day, but returned because of a recurrence of congestive heart failure. After an improvement of the heart failure, a coronary angiography was performed on the 20th hospital day. The coronary angiography revealed significant stenosis in three vessels. This elderly patient had congestive heart failure and triple-vessel coronary artery disease with transient alternating bundle branch blocks on serial electrocardiograms. Alternating bundle branch blocks and diffuse left ventricular dysfunction was considered to be induced by the aging process, postmyocarditic change of myocytes, and triple-vessel coronary artery disease in this case.

Aged↗
PubMed2003

May preservation solution affect the incidence of graft vasculopathy in transplanted heart?

Vasculopathy as a manifestation of chronic rejection of transplanted heart may limit long term patient survival. Development of vasculopathy can be associated with intima injury during ischemia and reperfusion. The purpose of this study was to determine whether preservation solution may improve posttransplant heart recovery and reduce the incidence of graft vasculopathy. From 93 to 99, 48 donors having received < 10 microg/kg/d of dopamine, were accepted for 40 male and 8 female recipients. They were prospectively assigned to three groups: Custodiol (n=15), Viaspan (n=17), and Celsior (n=16). Donor and recipient characteristics, cold ischemia time, organ procurement, transplantation procedure, and posttransplant immunosuppression were comparable among the groups. In Celsior group, spontaneous sinus rhythm recovered more often (12/16 pts, p=0.01) and higher cardiac output (6.5 l/min, p=0.03) was noted. No significant difference occurred among the groups in respect to inotropic support, cardiac index, pulmonary artery pressure, and biopsy performed during transplantation. The intravascular ultrasound (IVUS) imaging of the left anterior descending (LAD) coronary artery performed one year posttransplant, revealed significantly lower values of arterial area and arterial wall area in Celsior group. No significant difference in arterial lumen area occurred in the three groups. In Celsior group, lowest percent of intimal hypertrophy (24.23% +/- 9.83%, p=0.001) and less frequent (11/16 pts, p=0.001) chronic rejection (arterial hypertrophy=0.5 mm) was noted. Endomyocardial biopsy performed simulaneously to IVUS examination revealed no difference in pathologic lesions, except significantly less extensive fibrosis in Celsior group. During the 3.4 yrs of follow-up, freedom of biopsy proven acute rejection (=2(o)ISHLT) was significantly higher in Celsior (p=0.01). In this study Celsior allowed for better post transplant heart recovery and accounted for less incidence of vasculopathy and chronic rejection in the midterm follow-up.

Adenosine↗
PubMed1992

[A case of myxedema heart with serial endomyocardial biopsy].

We report a case of middle-aged woman with myxedema heart who presented congestive heart failure due to myocardial damage caused by myxedema, and showed reversible and irreversible myocardial change proven by serial endomyocardial biopsy. She was admitted to our hospital because of facial, peripheral edema and dyspnea. On admission, chest X-P revealed severe cardiomegaly (CTR 70%) and bilateral pleural effusion. Electrocardiogram showed low voltage. Echocardiogram and chest CT revealed a large amount of pericardial effusion. No significant stenosis was observed on a coronary arteriogram. Laboratory data showed elevated TC, CPK, LDH values and immunological test indicated high titer of thyroid test and microsome test. Thyroid function test revealed primary hypothyroidism with low T3, low T4 and high TSH levels. Replacement therapy for hypothyroidism in addition to digitalis and diuretics++ has been started. Seven months after initial evaluation, this therapy has resulted in dramatic clinical improvement. Transvenous right ventricular endomyocardial biopsy demonstrated vacuolated degeneration on admission and improvement of vacuolated degeneration with a slight degree of fibrosis after therapy. This pathological finding suggests that myxedema heart is able to produce both reversible and irreversible myocardial damage.

Aged↗
PubMed1992

[A case of hypereosinophilic syndrome exhibiting left ventricular systolic dysfunction].

A 16-year-old woman suffering from bronchial asthma since 2 years previously was admitted to the hospital because of high grade fever, dyspnea, skin eruption and arthralgia. Laboratory data revealed pronounced eosinophilia with elevated immunoglobulin E value. A chest X-ray film showed cardiomegaly with pulmonary congestion. Left ventriculograms showed diffusely reduced motion of the left ventricle (LV). Various clinical symptoms and laboratory data were resolved shortly after the administration of corticosteroids, but the LV dysfunction persisted for at least three months. Left ventriculograms 2 years later disclosed a marked improvement of the LV wall motion. In both the acute and the chronic phase, endomyocardial biopsy of both ventricles revealed non-specific histological findings comprising disarrangement of myocytes and interstitial fibrosis, suggesting post-myocarditis. This case was characterized by LV dysfunction possibly due to eosinophilic myocarditis associated with hypereosinophilic syndrome, and by its functional improvement with long-term corticosteroid therapy.

Adolescent↗