Five-week use of a monopivot centrifugal blood pump as a right ventricular assist device in severe dilated cardiomyopathy

Right heart failure is a critical complication in patients requiring mechanical ventricular support. However, it is often difficult to provide adequate right ventricular support in the acute phase. A 41-year-old woman diagnosed with dilated cardiomyopathy with severe right heart failure underwent implantation of a paracorporeal pulsatile left ventricular assist device (LVAD, Nipro Corporation, Tokyo, Japan) and a MERA monopivot centrifugal pump (Senko Medical Instrument Manufacturing Co., Ltd., Tokyo, Japan) as a right ventricular assist device (RVAD). The patient developed ischemic enteritis 3 weeks after surgery, necessitating fasting and reversal of anticoagulation therapy. A target international normalized ratio of 1.5 was selected, and aspirin administration was discontinued. Following recovery without thromboembolic events, the patient failed the RVAD discontinuation test. Five weeks after surgery, the monopivot centrifugal pump was exchanged for a pulsatile pump. No thrombus was evident on the centrifugal pump. The patient was undergoing cardiac rehabilitation at the time of this writing and awaiting heart transplantation.     

A clinical role for right ventricular endomyocardial biopsy

There is considerable uncertainty about the value of endomyocardial biopsy (EMB) in the diagnosis and management of patients with suspected primary myocardial dysfunction. To determine the clinical utility of this procedure in patients referred to our centre, we reviewed the clinical records and biopsy findings of the first 21 consecutive patients in whom we performed right ventricular EMB. Patients were divided into four groups according to the clinical indications for EMB: unexplained congestive cardiac failure and a dilated heart (Group 1: 11 patients); unexplained congestive cardiac failure and a non dilated heart (Group 2: three patients); unexplained cardiomegaly in the absence of cardiac failure (Group 3: one patient); suspected hypertrophic cardiomyopathy (HCM) (Group 4: six patients). Histological examination of EMB tissue obtained from all patients in Group 1 as well as the single patient in Group 3 showed non specific features judged to be compatible with a diagnosis of dilated cardiomyopathy. Accordingly, in all patients in Groups 1 and 3, a potentially treatable cause of primary myocardial dysfunction was excluded. Biopsy examination demonstrated the presence of a specific disease process in two of three patients in Group 2 (one patient had amyloidosis, the other endomyocardial fibrosis). In five of the six patients in Group 4, the biopsy findings were either diagnostic or suggestive of HCM. Our results suggest that EMB is a clinically useful tool in patients presenting with features suggestive of a primary myocardial disorder.     

Cardiac amyloidosis mimicking hypertrophic cardiomyopathy

Amyloid infiltration of the heart may frequently masquerade as other cardiac disorders. The extended use of echocardiography may contribute to an erroneous diagnosis of hypertrophic cardiomyopathy, as both conditions show several features in common. This was the case with the patient reported below. A low QRS amplitude, an increased right ventricular wall thickness, thickened cardiac valves, and a pericardial effusion may, however, indicate amyloid infiltration. The diagnosis of systemic amyloidosis of immunocytic origin was subsequently established in our patient. A definitive diagnosis of amyloid heart disease requires endomyocardial biopsy, but it is suggested that typical noninvasive findings together with demonstration of amyloid in an organ other than the heart is sufficient for a reliable diagnosis. In addition, systemic manifestations may contribute to a correct diagnosis in generalized amyloidosis. Our patient had features consistent with the rare muscle pseudohypertrophy syndrome, which is associated with immunocytic amyloidosis.     

Primary systemic amyloidosis leading to advanced renal and cardiac involvement in a 30-year old man

The case of a 30-year-old man with primary systemic amyloidosis is reported. Three months prior to admission the patient developed fever, night sweats, dyspnea, and bilateral ankle swelling. Recurrent left-sided pleural effusion led to further investigation when massive proteinuria with free monoclonal lambda chains in the urine became evident. Abdominal subcutaneous fat aspiration and renal biopsy confirmed the diagnosis of amyloidosis. Bone marrow biopsy and bone scan did not reveal multiple myeloma. Echocardiography showed a sparkling texture of the interventricular septum. Pulsed-wave Doppler recording of the left ventricular inflow profile showed the pattern of advanced cardiac amyloidosis consistent with markedly impaired diastolic heart function. Electrocardiogram-gated magnetic resonance imaging was carried out for noninvasive evaluation of cardiac function. The patient was started on repeated courses of melphalan, prednisone, and colchicine therapy. Despite increasing deterioration of renal function the therapy was tolerated quite well, and the patient is still alive 10 months after initial diagnosis. Although very rare in this age, primary systemic amyloidosis should be considered as a cause of pleural effusion, proteinuria, and congestive heart failure and should lead to further investigation.Abbreviations AL primary systemic amyloidosis - SAA serum amyloid A Correspondence to: I. Spyridopoulos     

Cardiac amyloid deposits in endomyocardial biopsies. Light microscopic, ultrastructural, and immunohistochemical studies

In four patients with unexplained, abnormal thickening of the interventricular septum as demonstrated by echocardiography, right ventricular endomyocardial biopsy revealed unexpected cardiac amyloid deposits that resulted in increased myocardial thickness and rapidly progressive heart failure. Light microscopically, amyloid was observed in the subendocardial layer, interstitium, and walls of the intramural arterioles. Electron-microscopically, the amyloid fibrils were adjacent to the basement membranes of the heart muscle cells and the vascular smooth muscle cells. Immunohistochemical typing with specific antibodies against different amyloid fibril proteins on glutaraldehyde-fixed paraffin sections revealed different amyloid types. In two patients with generalized idiopathic amyloidosis and in two others with amyloidosis in multiple myeloma, the A-lambda form was diagnosed. In a fifth patient, AA-amyloidosis was found in familial Mediterranean fever with cardiac manifestation without thickening of the interventricular septum. The amyloid deposits were located almost exclusively within the walls of the myocardial arterioles. The amount of amyloid as observed in the myocardial biopsies correlates with the rapidly progressive cardiac failure. It is suggested that in patients with abnormal thickening of the interventricular septum of unknown origin the diagnosis should be clarified by endomyocardial biopsy.     

A case of late onset cardiac amyloidosis with a new transthyretin variant (lysine 92)

A new transthyretin (TTR) variant (lysine 92), which causes late onset cardiac amyloidosis, is described in a 71-year-old man. The patient at first had syncope due to ventricular tachycardia and was admitted our hospital. Typical findings of cardiac amyloidosis were observed by echocardiography, and a diagnosis of systemic amyloidosis was made by rectal biopsy. The man died approximately 3 years and 6 months after first admission, with gradually worsening congestive heart failure. Pathological examination showed prominent amyloid deposits in the heart and the vascular wall of many organs including the liver, pancreas, kidney, lung, and gastrointestinal tracts. Amyloid protein of transthyretin type was indicated by immunohistochemical study, and DNA sequencing identified a novel mutation in the transthyretin gene encoding 92 glutamine --> lysine. A polymerase chain reaction-induced mutation restriction analysis with a mismatched antisense primer showed that the patient was heterozygous for the TTR Lys92 allele.     

Refractory right ventricular failure due to granulocytic sarcoma

A 72-year-old white man had granulocytic sarcoma (chloroma) characterized by right ventricular failure. Seven years before his final hospitalization, a diagnosis of agnogenic myeloid metaplasia was made on bone marrow biopsy, and the patient was treated with phosphorus 32. Three months before his death, the patient developed refractory right ventricular failure. Biopsy of a mass in the anterior abdominal wall demonstrated granulocytic sarcoma. The patient died 10 days after the biopsy was performed. Autopsy showed disseminated granulocytic sarcoma with massive encasement of the heart and the great vessels. This finding can, in retrospect, explain the hemodynamic abnormalities that led to the patient's death. This is, to our knowledge, the first case report of granulocytic sarcoma diffusely involving the heart and causing refractory right ventricular failure in a patient with a long-standing history of agnogenic myeloid metaplasia.     

Diagnostic use of the endomyocardial biopsy: a consensus statement

The Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology created a task force to write a consensus document on when and how endomyocardial biopsy is of help for clinicians in the diagnosis and treatment of patients with heart failure, arrhythmias, and cardiac masses. Endomyocardial biopsy is the gold standard for a definitive diagnosis in disease entities like myocarditis, cardiac allograft rejection, and infiltration/storage myocardial disorders. Use of molecular biology techniques is mandatory to obtain specific information on etiology and pathogenesis and should be carried out as an investigation complementary to histology and immunohistochemistry. Given the complexity of these investigations, endomyocardial biopsy should be performed in or in collaboration with cardiac pathology referral centers, where the whole armamentarium of pathological investigation is available, including molecular techniques. Optimal use of the endomyocardial biopsy requires clinicopathologic correlations.     

Primary cardiac amyloidosis with 20-year survival

BACKGROUND: The natural history of primary amyloidosis is poor, and for patients with symptomatic cardiac involvement, survival is generally less than 6 months. Even among treated patients with amyloid heart disease, survival beyond 5 years is rare. CASE REPORT: We report a patient with primary cardiac amyloidosis who is currently alive 20 years after his initial diagnosis. The extent and subtype of amyloid were documented by endomyocardial biopsy both at the time of initial diagnosis and 20 years later. To our knowledge, this is the longest survival ever reported for a patient with cardiac involvement by primary amyloidosis. CONCLUSION: The remarkably long stabilization of amyloid deposition in this patient may be attributed to early diagnosis, early institution of therapy, and, possibly, favorable genetic factors.     

An autopsy case of giant cell myocarditis probably due to a non-steroidal anti-inflammatory drug

An autopsy case of giant cell myocarditis (GCM) in a 74-year-old woman is presented. She suffered from hepatic dysfunction, skin eruption and disseminated intravascular coagulation due to the side-effects of a non-steroidal anti-inflammatory drug. After admission, heart failure progressed rapidly, and the patient died suddenly. At autopsy, her heart was slightly enlarged and the heart muscle was thickened with many small whitish nodules. She was diagnosed with GCM because of the infiltration of multinuclear giant cells, histiocytes, eosinophils and lymphocytes into the heart. We did not find any similar lesions in any other organs. Giant cell myocarditis, the etiology of which is not defined, is a rare disease with unfavorable prognosis. This case suggests the possibility of drug-induced GCM.     

Fulminant toxoplasmosis in a heart transplant recipient

Toxoplasma gondii infections in heart transplant recipients emerge in most cases as newly acquired infections of the immunocompromised sero-negative patient from an exogenous source, usually the donor organ. We report on a 64-year-old heart transplant recipient who developed pneumonitis, myocarditis, and hyperacute encephalitis three weeks after transplantation. Histopathological examination of an endomyocardial biopsy revealed fulminant T. gondii infection. Although appropriate chemotherapy was administered immediately, the patient died the next day. Our case demonstrates that if a histological diagnosis is not rendered in time, fulminant toxoplasmosis may lead to a fatal outcome. In conclusion, a general screening of the donors and recipients for opportunistic infections, including toxoplasmosis, and an appropriate prophylaxis should always be considered.     

Multimodality imaging and the emerging role of cardiac magnetic resonance in autoimmune myocarditis

Autoimmune responses and inflammation are involved in the excess cardiovascular risk observed in patients with systemic inflammatory diseases. Autoimmune myocarditis is a presentation of an inflammatory reaction of the heart during the course of autoimmune disorders, with most cases seen in systemic lupus erythematosus. Early diagnosis is of great significance because of the likelihood of progression to severe and potentially fatal complications such as arrhythmias, heart block, and heart failure. The clinical presentation of the disease is silent leading to delayed diagnosis when dilated cardiomyopathy or heart failure has already advanced. Therefore, a major issue is whether the diagnosis of myocarditis will continue to require invasive procedures such as endomyocardial biopsy or can be achieved with non-invasive methods. There is increasing evidence that noninvasive cardiac imaging, including tissue Doppler echocardiography and cardiac magnetic resonance (CMR), is able to detect subclinical cases and aid in the initiation of specific treatment when it is more likely to be effective. CMR in particular, has emerged as an important technique in the evaluation of myocarditis using three types of images: T2-weighted (T2-W), early T1-weighted (EGE) images taken after 1 min, and delayed enhanced images (LGE) taken 15 min after the injection of contrast agent. If 2/3 of the imaging sequences are positive, myocardial inflammation can be predicted or ruled out with a diagnostic accuracy of 78%. As our understanding of disease mechanisms improves, multimodality imaging may aid in the development of new diagnostic and therapeutic strategies for this potentially devastating complication of systemic inflammation, but further studies are needed to formally evaluate this.     

Toxoplasmosis of donor and recipient hearts after heterotopic cardiac transplantation

Toxoplasmosis of both donor and recipient hearts was diagnosed by means of endomyocardial biopsy specimens after heterotopic cardiac transplantation for dilated cardiomyopathy. Before transplantation, the donor had raised antibody titers to Toxoplasma, and the recipient was negative. When toxoplasmosis was diagnosed on the basis of endomyocardial biopsy specimen, the recipient had a greatly elevated antibody titer of 1:1,027. This suggests that the infection could have been transferred with the donor heart. The mononuclear cell response elicited by disrupted toxoplasmic cysts interferes with the diagnosis of rejection in graft biopsy specimens. Electron microscopy is valuable in confirming a light microscopic diagnosis of toxoplasmosis. Drug therapy eradicated the toxoplasmosis, but the patient died later of tuberculous meningitis.     

Acute parvovirus B19 infection associated with myocarditis in an immunocompetent adult

Inflammatory heart disease is causally linked with progressive left ventricular dysfunction and congestive heart failure. In childhood, infection with parvovirus B19 (PVB19) is usually benign, causing erythema infectiosum. However, severe fetal PVB19 infection may be associated with hydrops fetalis and fetal death caused by myocarditis. Here we report a PVB19-induced myocarditis in a previously healthy 37-year-old patient admitted to the hospital because of chest pain and dyspnea due to left ventricular dysfunction. Four weeks after the onset of symptoms, we found lymphocytic infiltrates and PVB19 genome in left ventricular endomyocardial biopsy specimens. Consistently, acute PVB19 infection was indicated serologically by elevated IgM titers and the presence of PVB19 genome in peripheral blood lymphocytes. In conclusion, PVB19 infection may be complicated by acute myocarditis in immunocompetent adults. Because PVB19 myocarditis may progress to chronic dilated cardiomyopathy, early diagnosis by endomyocardial biopsy is important to initiate anti-inflammatory treatment.     

Three patients of transthyretin amyloidosis in a Japanese family with amyloidogenic transthyretin Thr49Ser (p.Thr69Ser) variant

Transthyretin (TTR)-related hereditary amyloidosis (ATTRv) is a rare autosomal dominant disorder that is caused by pathogenic missense mutation of the TTR gene. As of today, more than 150 TTR gene variants have been reported to occur as causal mutations. Herein, we present three familial patients of ATTRv caused by the Thr49Ser (p.Thr69Ser) variant, including their phenotypes and penetrance.The first patient was a 68-year-old woman with a history of carpal tunnel syndrome, who was referred to our department with heart failure symptoms. Echocardiography, ^99mTechnetium (Tc)-pyrophosphate scintigraphy, and myocardial biopsy confirmed her diagnosis as TTR-related amyloidosis. Genetic testing for the TTR gene was performed, which confirmed the presence of a Thr49Ser (p.Thr69Ser) variant. The second patient, a 45-year-old woman, who was the niece of the first patient, presented with dyspnea on exertion. Her clinical manifestations included cardiac symptoms in addition to polyneuropathy. Similarly, myocardial biopsy showed TTR amyloid deposition within cardiac tissues, and TTR gene sequencing detected the presence of a Thr49Ser (p.Thr69Ser) variant. The final patient was a 42-year-old man, who was the nephew of the first patient, presented with numbness in his hands. Abdominal wall fat pad biopsy showed TTR amyloid deposition, and TTR gene sequencing was performed considering the familial history to confirm the presence of Thr49Ser (p.Thr69Ser) variant. No cardiac symptoms or dysfunctions have been observed yet, but imaging has detected TTR amyloid deposition in the heart.The present three patients with Thr49Ser (p.Thr69Ser) variant showed variation in phenotypes including cardiac and neurological manifestations at a fairly young age. In addition, the familial relationship in this report suggested that this variant is highly penetrant. Early genetic diagnosis due to collecting the genetic information from family medical history may be beneficial to improve patient prognosis via early therapeutic intervention.     

Temporary use of the Jarvik-7 total artificial heart before transplantation

Between October 24, 1985, and July 31, 1986, the Jarvik-7 total artificial heart was implanted into six moribund patients in an attempt to test its potential as a bridge from almost certain death to cardiac transplantation. Four of these patients are now well and at home after implantation of the device and subsequent cardiac transplantation. Before transplantation, one patient died with sepsis and multiorgan failure that preceded implantation of the artificial heart. Another patient died with acute rejection 60 days after cardiac transplantation. Fifty-two days of total mechanical support with the artificial heart were accumulated in these six patients, and although the device worked flawlessly and no clinically apparent thromboembolic events occurred, each artificial heart contained areas of macroscopic aggregations of platelets and thrombi. The results of this trial indicate that in properly selected cases, direct benefit to the patient can be obtained when the Jarvik-7 artificial heart is used as a bridge to transplantation.     

Cardiac presentation of non-Hodgkin's lymphoma

We present a case of non-Hodgkin's lymphoma with massive cardiac involvement in a previously well 65-year-old man, presenting with pericardial tamponade and heart failure of recent onset. Results of echocardiography and of pericardial and pleural fluid cytology suggested the diagnosis. Within two weeks the patient's condition progressed to complete heart block and he died. Primary cardiac tumors are rare when compared with metastatic involvement of the heart. Their presentation includes congestive heart failure, cardiomegaly, pericardial effusion, and sudden death. The clinical diagnosis has seldom been made.     

Ultrastructural and immunohistochemical analysis of biopsy-proven chronic active mycocarditis with numerous clusters of lymphocytes

 A 60-year-old women was admitted to our hospital with deteriorating congestive heart failure. Although the diagnosis of active myocarditis was confirmed by right ventricular endomyocardial biopsy, this patient died of refractory heart failure during corticosteroid treatment. Numerous lymphocytic clusters were observed microscopically in the heart at autopsy. Most of the infiltrating cells in the clusters were positive for CD 8, HAM 56 or MHC class 2 antigen; few cells were positive for CD 56. Expression of perforin was found in some of the infiltrating cells. Electron microscopic examination revealed small lymphocytes adhering to the surface of injured cardiac myocytes. Close contact of these lymphocytes to macrophages was shown in the clusters. ICAM-1 and MHC class 1 antigens were strongly expressed in the cardiac tissue. These results indicate that cytotoxic T lymphocyte-mediated cytotoxicity had continued to operate during immunosuppressive therapy. Corticosteroids may not be suitable for the treatment of chronic active myocarditis when persistent expression of ICAM-1 is observed. Received: 24 September 1997 / Accepted: 17 April 1998     

Primary cardiac lymphoma in immunocompetent patients: a report of three cases and review of the literature

Primary cardiac lymphoma is an extranodal non-Hodgkin's lymphoma exclusively located in the heart and/or pericardium, extremely rare in immunocompetent patients, and more frequent in immunodepressed patients. We present 3 retrospectives cases of primary cardiac lymphoma in immunocompetent patients and review 35 cases reported in the literature. Two patients were adults and one was a child. Primary cardiac lymphoma presented with constitutional symptoms in two cases and superior vena caval syndrome in one case. Diagnosis of a tumor mass was made in all cases by transthoracic echocardiography. Primary cardiac lymphoma arose in the heart right chambers in two cases. Histological diagnoses, obtained after thoracotomy, were diffuse large B-cell lymphoma in two cases, and Burkitt's lymphoma in one case. All three cases received chemotherapy, combined with radiotherapy in one patient. Of our patients, 2 are alive and asymptomatic 12 months and 33 months after diagnosis. In conclusion, diagnosis of primary cardiac lymphoma is difficult due to non-specific clinical manifestations and should be considered in patients with a cardiac mass sometimes with pericardial effusion. It is confirmed using transthoracic echocardiography and magnetic resonance imaging and certified using cytology or open biopsy. The only effective treatment is chemotherapy, but prognosis remains poor.