Márta Hubay

Rapid recurrence of an inflammatory myofibroblastic tumor in the right ventricular outflow tract

We describe an unusual case of rapid recurrence of a previously excised inflammatory myofibroblastic tumor of the right ventricular outflow tract in a 5-month-old infant. The infant is asymptomatic 18 months after the second surgery. The very rare cardiac involvement, and the early relapse of the inflammatory pseudotumor, to the best of our knowledge, is a unique combination. The inflammatory myofibroblastic tumor, as known as a pseudotumor or plasma cell granuloma is an uncommon reactive lesion with unknown aetiology. It is found most commonly in the lung and a number of visceral organs, such as the spleen, liver, ileum, salivary glands, urinary bladder, larynx or brain or in the retroperitoneum and lymph nodes. To our knowledge only 9 cases have been published of such tumor arising within the heart.

No mutation but high mRNA expression of Coxsackie-Adenovirus Receptor was observed in both dilated and ischemic cardiomyopathy

The most common causes of acute myocarditis and the possible consequence of dilated cardiomyopathy are virus infections. The receptor of the two most common viruses connected to these myocardial diseases was identified as Coxsackie-Adenovirus Receptor. The purpose of this study was to assess Coxsackie-Adenovirus Receptor mRNA expression in the myocardium and search for mutations in the Coxsackie-Adenovirus Receptor gene to compare dilated, inflammatory and ischemic cardiomyopathy with control group. All the myocardial samples were obtained from 35 explanted hearts during heart transplantation, than DNA and RNA were isolated from the muscle samples. cDNA was generated from RNA using reverse transcription, and real-time PCR was performed with relative quantification by β-actin gene as endogenous control. Using DNA extracted from the myocardial samples, we sequenced all the seven exons of the Coxsackie-Adenovirus Receptor gene. Coxsackie-Adenovirus Receptor mRNA expression was higher in both ischemic and dilated cardiomyopathy groups than in inflammatory cardiomyopathy and healthy control groups. Sequencing of CAR gene showed no sign of mutation. Therefore, the sequences result of CAR exons did not show any mutation or polymorphism, that explains a determinant role of CAR in dilated or ischemic CM. Our results suggest that high mRNA expression of Coxsackie-Adenovirus Receptor may support its role in regeneration of the damaged myocardium rather than having any role in viral mediated heart disease.

The Role of Viral Infections in the Development of Dilated Cardiomyopathy

Enteroviruses (EVs) are the most frequent pathogens in myocarditis and in the subsequently developing dilated cardiomyopathy as well. Furthermore, persistence of other viruses might play a pathogenic role in the evolution from myocarditis to dilated cardiomyopathy. Explanted heart of 28 patients, who underwent heart transplantation were screened for EV, AdV3 and HHV6 sequences in order to assess the incidence of cardiac viral infection that may be implicated in the pathogenesis of cardiomyopathy, and estimate viral distribution in the myocardium. Viral sequences were extracted from five different regions of the hearts. Nested PCR was used to amplify conservative regions of AdV3, HHV6 and EVs. Histological examination was performed on routinely processed myocardial samples. AdV3 was verified in one fourth of the patients. ADV3 and HHV6 sequences coexisted in one case with inflammatory cardiomyopathy. Some patients had more than one positive area of their heart. AdV3 positive right ventricular samples were double in amount compared to the left ones. None of the patients had positive result for EV. This is the first occasion to identify AdV3 (a mainly respiratory infective virus) sequence in explanted hearts of cardiomyopathy patients. Though the clinical importance of our results is still unclear, AdV3 could be a new member of the viral group with possible pathogenic effect on the myocardium. Regional distribution of viral sequence location confirmed that the right ventricular wall as a biopsy sampling site might be adequate for endomyocardial biopsy pro diagnostic purposes.

Successful cardiac resynchronization therapy after heart transplantation.

We describe a case of a 56-year-old male patient, who developed refractory dilated cardiomyopathy 5 years after heart transplantation. An atriobiventricular pacemaker was implanted when indication criteria of cardiac resynchronization therapy (CRT) were seen. The intraventricular dyssynchrony was significant before CRT, while synchronous contraction was demonstrated later with the beneficial reverse remodelling of the left ventricle. Resynchronization therapy resulted in significant improvement of the patients clinical parameters. The success of this therapy points out the possible role of CRT in the treatment of chronic allograft failure after heart transplantation.

Molecular biological virus identification in dilated cardiomyopathy

UNLABELLED Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy. Some publications shed light to the role of other viruses in this disease as well. Our molecular investigation has demonstrated that adeno- and herpes viruses might also frequently occur in dilated cardiomyopathy. AIM The aim of our study was to screen virus genomes in heart tissues from heart-transplanted patients to prove their possible role in the pathogenesis of dilated cardiomyopathy. METHODS DNA and RNA were isolated from five regions of the heart muscle. Amplification for Adenovirus Type 3, Human Herpes Virus Type 6 and Enterovirus genomes were performed by nested-Polymerase Chain Reaction. Finally the virus-positive samples were direct sequenced. RESULTS In 2 patients Adenovirus Type 3 and in 1 patient both Adenovirus Type 3 and Human Herpes Virus Type 6 were detected. No enteroviruses were found in any heart tissue. CONCLUSIONS In our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues. The identified viral sequences proved previous viral infection, which could have played a role in the development of dilated cardiomyopathy. Detection of different viruses in the myocardium by molecular biological examinations might contribute to adequate treatment of these patients.

Hemodynamic Effects of the Light Stabilizer Tinuvin 770 in Dogs In Vivo

Introduction: Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate, Ciba-Geigy, Basel, Switzerland] is a UV light stabilizer that is a component of many plastic materials used world-wide in the medical and food industries. We report on the acute hemodynamic effects of Tinuvin 770 examined in dogs. Materials and Methods: Tinuvin 770 was dissolved in a mixture of saline and ethanol (1:1 v/v) and was administered to 12 intravenously narcotized and respirated dogs in increasing doses (T1-T7: 1, 3.3, 6.6, 10, 33.3, 66.6 and 100 mg, respectively). The doses were given as bolus injections over a three minute period, and the effects were recorded for 12 minutes. The vehicle was used as a control. Hemodynamic parameters (heart rate, blood pressure, end-diastolic pressure, dp/dt, cardiac output) and ECG were monitored continously. Results: At doses T1-T4, systolic and diastolic blood pressures, mean pressure and ventricular contractility were significantly decreased without significant changes in cardiac output, heart rate, or PQ interval. At doses T5 and T6, declines in blood pressure and myocardial contractility were observed. At doses T6 and T7, heart rate and PQ interval decreased substantially. Irreversible circulatory failure occured in one dog after administering dose T6 and in 8 dogs following dose T7. Conclusion: Tinuvin 770 induces acute hemodynamic alterations. In lower doses, it causes peripheral vasodilatation, however at higher doses acute cardiac failure occured. Plastics containing Tinuvin 770 should be used with care in medical practice and the laboratory.

Patchy Myocardial Pattern of Virus Sequence Persistence in Heart Transplant Recipients—Possible Role of Sampling Error in the Etiology

BACKGROUND The pathway from viral myocarditis to end-stage heart failure is commonly accepted, but diagnosis of virus-mediated myocardial injury remains challenging. Virus persistency in the myocardium may accelerate ventricular failure; thus, a precise diagnosis of virus persistency may prevent the development of end-stage heart failure. METHODS We performed a systematic investigation on the sampling error of viral diagnostics in heart transplant recipients: Transmural samples from 5 regions of the explanted hearts from recipients during heart transplantation were amplified using entero-, adeno-, and herpesvirus sequences and histologic examinations performed. RESULTS We examined 175 myocardial samples from dilated cardiomyopathy and 100 samples from 20 forensic medicine patients. Seven patients were positive for the examined viruses: 10 positive regions for adenovirus, and 1 positive region for herpes virus DNA, but none for enterovirus. A focal myocardial pattern was detected for adenovirus. CONCLUSION Our results with the patchy myocardial viral persistence may explain possible false-negative results related to virus-mediated etiology among end-stage dilated cardiomyopathy patients. Therefore, repeated endomyocardal biopsies, and multiple cardiac samples are recommended to be obtained to evaluate the etiology of heart failure, thus reducing the occurrence of end-stage heart failure and decreasing the number of patients requiring heart transplantation.

Spontaneous aortic rupture during pregnancy

Aortic dissection is a rare entity. Half of the aortic dissection cases occur during pregnancy in women under the age of 40. The authors report a case of a multiparous woman at the third trimester of her sixth pregnancy, who died from a sudden and intractable cardiovascular shock. Autopsy revealed the dissection of the ascending aorta. The case is interesting, especially because in the pregnant womans family it was not the first sudden death during pregnancy. Authors review the relevant literature regarding the symptoms and the genetic basis of this rare but potentially lethal complication of pregnancy.

[Arrhytmogenic right ventricle--prognostic significance of exercise test].

UNLABELLED The authors summarize the present knowledge on arrhythmogenic right ventricular cardiomyopathy/dysplasia. Limited data are available about natural history of asymptomatic patients with arrhythmogenic right ventricle cardiomyopathy/dysplasia, who have a ventricular tachycardia during exercise test. A 25-year old female patient was treated with osteosynthesis because of ankle injury. Cardiology consultation was performed because of an abnormal ECG. Physical examination was normal. ECG showed a normal sinus rhythm, left axis deviation, negative T waves in leads II, III, aVF and V2-V6. Chest X-ray and laboratory findings were normal. Echocardiography showed normal left ventricular ejection fraction along with inferior akinesis and dilated right ventricle. Bicycle exercise test revealed a good exercise tolerability (9 MET), and after sporadic ventricular extra systoles ventricular tachycardia developed lasting for 3 minutes, which spontaneously stopped after aborting the test and performed abdominal strain. MRI was performed which has shown normal left ventricular size, wall motion and ejection fraction and depressed right ventricle function (ejection fraction 31.6%) enlarged right ventricular end-systolic and diastolic volumes, hypo-akinetic regions without aneurysm and bulging. No contrast enhancement was seen in the thin right ventricular wall. According to abnormal ECG and MRI findings arrhythmogenic right ventricle cardiomyopathy/dysplasia was diagnosed. No ICD implantation was indicated because the patient was asymptomatic, and no sudden cardiac death occurred in the family. Three month later the patient was found dead. At autopsy the right ventricular chamber was markedly enlarged, with multiple translucent areas of fatty accumulation accompanied with extended myocytes loss. There was a characteristic triangle dysplasia: the inflow, outflow tracts and apical areas. The coronaries were free of atherosclerosis. Mallorys phosphotungstic acid-hematoxilin stain demonstrated the presence of fibrosis within the scattered myocardium. CONCLUSION malignant ventricular arrhythmia provoked by exercise test in an asymptomatic arrhythmogenic right ventricle cardiomyopathy/dysplasia patient with negative family history should be an indication for ICD implantation.