Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.

Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Breakthrough in the Transplantation of Thoracic Organs in Hungary.

In 2016 the focus was, by all means, on the transplantation on thoracic organs. More than 50 heart transplantations were performed in this year. With this achievement, the Hungarian Heart Transplantation Program became one of the leading programs in the world. In the Thoracic Surgery Unit of the National Institute of Oncology and the Thoracic Surgery Department of Semmelweis University the first successful lung transplantation was carried out on December 12, 2015 when the Hungarian Lung Transplantation Program was launched.

Active metabolites resulting from decarboxylation, reduction and ester hydrolysis of parent drugs.

Decarboxylation, reduction and hydrolysis can yield active metabolites from the parent drug. Major therapeutic indications and metabolic routes of these drugs are reviewed. Changes in the logP values (determined and calculated) from the parent drug to the active metabolite show certain characteristics in comparison to other phase I metabolic alterations. Metabolic decarboxylation of parent drug is commonly associated with increase in lipophilicity. However, in some cases, decarboxylation may cause a reduction in lipophilicity. Ester hydrolysis generally unmasks either the polar carboxylic or hydroxyl group with the outcome of an increase in hydrophilicity. On the contrary, hydrolysis of phosphate ester means a huge increase in the lipophilic character of the drug, as the highly polar phosphate group is removed.

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.

[Experience with surgical treatment of prosthetic valve endocarditis]. / Múbillentyú-endocarditis sebészi kezelésével szerzett tapasztalataink.

Prosthetic valve endocarditis (PVE) is a rare but dangerous complication that may occur after the implantation. The authors retrospectively summarize their 11-year experience in treating PVE. 2357 prosthetic valve (PV) implantations were performed over 11 years at the Department of Cardiovascular Surgery, Semmelweis University, Budapest, PVE was found to be the indication for operation in 1.8% of the cases (43/2357). 43 surgical interventions were carried out on 38 patients (mean age: 52.5 yrs, male/female ratio: 25/13). Blood cultures were positive in 86% and negative in 14% of the cases. The infected PV-s were replaced emergently (14%), urgently (79%) or electively (7%). The explanted valves were aortic in 55% and mitral 45% of the cases, 63% were mechanical and 37% biological. PVE followed the primary PV implantation in less than a year in 39.5%. Infected environment during the primary PV implantation was found to be a predisposing factor for the late endocarditis episodes. The mean age of the infected and explanted aortic bioprosthetic valves was significantly higher than that of explanted mechanical valves (p < 0.05). No such difference could be found at the mitral valves. The explanted valves were replaced by mechanical (75.5%) or biological (22.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%) devices. Homograft was implanted once. Early postoperative mortality of the primary PV replacements was 10.5%. Endocarditis reoccurred in 20% of the cases. Means follow-up duration was 45.5 months. Two-, five- an 10-year survival were 75%, 64% and 51% respectively. In conclusion in the surgical treatment of PVE, bioprosthetic and mechanical valves are suitable alternatives as opposed to homografts and freestyle stentless valves.

[Coronary artery bypass grafting without extracorporeal circulation]. / Koszorúérmútétek extrakorporális keringés alkalmazása nélkül.

At the Department of Cardiovascular Surgery of Semmelweis University, Budapest we have performed 57 coronary bypass operations without using cardiopulmonary bypass between 1996 and September 2001. Due to the learning phase we preferred cases of 1-2 wessel diseases, and revascularisation necessary on the anterior surface of the heart. In the beginning the stabilization of the operative field was ensured by manual methods, then by applying mechanical stabilization devices (Octopus 2, Genzyme). As to the type of operative indication overwhelmingly elective operations were performed. REDO procedure, i.e. repeated coronary bypass operation was carried out in 2 cases. Forty-eight patients recovered without complication. Two patients died, one of them suffered perioperative infarction, the other died due to cerebral complication. Total mortality was 3.5%. As a consequence of cardiac ischaemia in the direct postoperative period, we performed emergent coronary ballon dilatation (PTCA) in two cases. In three cases we experienced perioperative infarction. We followed up our patients by way of interview and telephone interview. The follow-up is 95%, the average follow-up time is 15 months. Significant cardiac event (infarction, PTCA or REDO coronary operation) took place in the case of 7 patients. In the majority of our patients the operation resulted in an improvement of condition, 43 patients are free from angina.

[Life expectancy in Down syndrome infants and children with congenital heart defects, 1974-1997]. / A Down-szindrómás szívbeteg csecsemók és gyermekek életkilátása 1974-1997 között.

Authors analysed 359 cases with Down's syndrome and congenital heart defects registered between 1974-1997 in Hungary. The total death rate was 19.9% (70 cases). Mortality in the operated group (85 cases) was 10.5% (9 patients), in the non-operated group (274 cases) 22.2% (61 patients). The death rate was lower in the group with early primary reconstruction (2.3%) than in the group with palliation + reconstruction (15.3%), or in the group with only palliative procedure (20%). These results indicate that the life expectancy of infants and children with Down's syndrome and congenital heart disease after early primary reconstructive procedure is the same as in Down syndrome patients without cardiac defects. The prognosis depends on the patient's social circumstances. The results after correct surgical procedure in patients with the same cardiac defect are similar to that of the patients with or without Down's syndrome.

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.

[Primary reconstruction of the common truncus arteriosus in infants, using modified pulmonary homograft]. / Truncus arteriosus communis primer rekonstrukciója csecsemökorban, méretre alakított pulmonalis homograft felhasználásával.

Truncus arteriosus communis (TAC) is a complex heart disease, it presents 1% of the congenital heart defects. A 7 weeks old infant with cardiac failure was operated on with TAC. The bicuspidized (14 mm diameter) pulmonary homograft valved conduit was used to reconstruct the right ventricular outflow tract (RVOT). The sternum closure was delayed. The important points of the indications for the surgical management of TAC: 1. Management or prevention of the pulmonary hypertensive crisis. 2. Patient's age. 3. Reconstruction of the RVOT (choices: homograft, dacron valve conduit, autologous pericardial valve conduit, porcine aortic root, direct anastomosis of the pulmonary trunc to the right ventricle). The surgical management is based on the optimal combination of these three important points. This is the first successfully performed primary surgical repair of an infant with TAC using modified pulmonary homograft in Hungary.

[Closure of the patent ductus arteriosus by means of cardiac catheterization]. / Ductus Botalli persistens zárása szívkatéteres módszerrel.

Authors report their results with transcatheter closure of patent arterial duct during a period of 1 year. Thirty patients underwent the procedure at the mean age of 5.22 yrs (range 5 mos-22.3 yrs) and mean bodyweight of 19.1 kg (range 5.8-73 kg). There were 9 males and 21 females. The diagnosis of the patent arterial duct was established by physical examination and noninvasive techniques. The procedures were attempted in all patients above 5 kg bodyweight with patent arterial duct and normal pulmonary artery pressure, irrespective of the shunt-size. All procedures were performed under general anesthesia in one session with the diagnostic cardiac catheterisation. Transcatheter closure was successful in 29 patients. In one patient the device embolized into the left pulmonary artery, snaring was unsuccessful, surgical closure of the patent duct and removal of the device took place uneventfully. Control aortography 15 minutes after the coil placement showed insignificant residual shunt through the patent duct in 8 patients (27%), while echocardiography at 1 month proved complete closure in all. The patients were followed by noninvasive methods. No mortality was observed. Authors emphasize the low risk and cost-effectiveness of the procedure. They stress the importance of the patients selection. Authors applied the technique for the first time and introduced it to the regular patient-care practice in Hungary.

Candida endocarditis in an infant.

Infective endocarditis is a rare disease in infants. A 1-year-old boy with a large Candida albicans vegetation in the right atrium and superior vena cava was operated on successfully. During the newborn period he had had a right transverse colostomy for Hirschsprung's disease. Ten months later a subsequent rectosigmoidectomy and direct anastomosis were performed, but because of peritonitis that followed a leak at the site of the anastomosis parenteral nutrition was needed for 8 weeks. The probable source of Candida was an infected intravenous line.

Mitral valve anomalies obstructing left ventricular outflow.

This paper reports on two cases of more uncommon types of subaortic stenosis. A 2-year-old boy was found with accessory mitral valve leaflet (AMVL) attaching to the anterior leaflet, ballooning into the subaortic ventricular septum associated with a discrete subaortic membrane. The obstruction was successfully relieved by removal of the AMVL and resection of the membrane. A 19-day-old newborn with accessory tissue on the mitral valve (AMVT) causing subaortic stenosis, subaortic ventricular septal defect (VSD) and patent ductus arteriosus was operated on successfully. Accessory tissue excision through the VSD, VSD patch closure and ductus ligation were performed.

[Successful multi-step management of developmental heart defects after intrauterine diagnosis]. / Intrauterin diagnosztizált összetett szívfejlódési rendellenesség többlépcsós sikeres sebészi korrigálása.

At 28th week of gestation a conotruncal malformation with ventricular septal defect was diagnosed by fetal echocardiography. Postnatal echocardiographic and angiocardiographic examinations confirmed the diagnosis of conotruncal malformation (pulmonary atresia, ventricular septal defect, patent ductus arteriosus, aortopulmonary collateral arteries). The unifocalization (age: 11 months) and total correction with aortic homograft (age: 7 years) were performed. To our knowledge our case is the first whose intrauterine diagnosis of complex congenital heart disease was confirmed after delivery and had successful two-stage surgical management.

[Intraoperative epicardial echography in infancy and childhood for the evaluation of the results of surgical correction of congenital heart defects]. / Intraoperatív epicardialis echocardiographia csecsemö- és gyermekkorban a veleszületett szívhibák mütéti eredményének megítélésére.

Intraoperative epicardial echocardiography (IEE) is very useful to assess the result of the surgical procedure. In infancy and childhood the authors performed 32 IEE (using high frequency transducer) out of 193 operations with congenital heart diseases. As a result of IEE study the surgical procedure was extended in 5 cases, as follows: closure of patent ductus arteriosus, exchange of transanular patch, repeated mitral repair, prosthetic mitral valve implantation, and correction of residual right to left shunt. No early or late reoperation was necessary in the remaining cases. Follow up echocardiography and autopsy in 4 cases confirmed the diagnosis of the IEE. The results suggest, that IEE will be the standard method for quality control of surgical procedures in congenital heart disease.

[Total cavo-pulmonary anastomosis in heart surgery for the correction of univentricular heart]. / Teljes cavopulmonalis anasztomózis az univentricularis szív sebészi korrekciójában.

The total cavopulmonary anastomosis is one of the alternative surgical procedures which can be performed in the management of the most complicated congenital heart diseases. It was the first time in Hungary that this surgical management was performed successfully in a girl with univentricular heart, pulmonary valve stenosis, malposition of the great arteries, who was operated on palliative procedure previously.

[Non-invasive and invasive assessment of the function of aortic valve homografts in infancy and childhood]. / Homograft aorta billentyü conduit funkciójának noninvazív és invazív vizsgálata csecsemö- és gyermekkorban.

Study population involved 21 pts with complex congenital heart disease after corrective surgery using homografts between the years 1986 and 1992. Diagnoses included double outlet right ventricle, tetralogy of Fallot, transposition of great arteries, truncus arteriosus, pulmonary atresia with VSD, corrected transposition with pulmonary stenosis, and absent pulmonary valve. Pts age at surgery ranged from 18 days--to 15 yrs mean, 6.7 yrs. Time interval between surgery and diagnostic procedures was 8 days--6 yrs (mean 11 months). All pts were studied by Echo/Doppler. 2 pts by TEE and 3 pts by MRI. 6 pts had cardiac catheterisation. Distal (5) or proximal (1) stenosis was present in 6 cases. The severity and the type of stenosis was correctly identified by noninvasive technique compared to invasive findings. Homograft valve regurgitation was mild (4) or moderate (3). In two pts severe insufficiency was associated to homograft endocarditis. Postoperative residual shunts were found in 8 pts. Homograft stenosis can correctly be diagnosed using Echo/Doppler technique. Distal stenosis was more frequent than proximal. Homograft tends to become insufficient, but severe incompetence did not occur except in endocarditis.

[Successful surgical correction of persistent truncus arteriosus by an aortic homograft]. / Truncus arteriosus communis sikeres sebészi korrekciója aorta homograft beültetéssel.

After palliative procedure a 2 years old girl with congenital heart disease was corrected with aortic homograft. Truncus arteriosus is a rare congenital heart disease and this is the first successfully corrected case in our country. Using homograft in this age group improves the early and late result of this type of corrective surgery.

[Vascular ring and pulmonary loop: experience with the surgical treatment]. / Sosudistoe kol'tso i legochnaia petlia: opyt khirurgicheskogo lechenia.

Operation was carried out on 143 children (aged from 5 days to 16 years) for tracheobronchial obstruction caused by vascular rings. A double arch of the aorta was found in 50 patients, double arch of the aorta with atresia of the left arch--in 50 patients, right arch of the aorta with ligamentum arteriosum--in 30, left arch of the aorta with an aberrant right subclavian artery--in 10, and a pulmonary loop in 3 patients. Stridor was the main clinical manifestation of the vascular ring. The diagnosis was established by means of two-projection chest radiography and esophagography with a barium meal, bronchoscopy, and angiography. The surgical approach was gained through a posterolateral (left or right) thoracotomy. No deaths occurred during the operation. Two infants died in the postoperative period from a severe bacterial infection of the respiratory tract. On the basis of a rich clinical experience the authors came to the conclusion that the presence of a right aortic arch (except for cases with situs inversus) is always pathognomic because it either causes the appearance of a vascular ring without any intracardiac anomaly, or it may be combined with a congenital heart disease in which a vascular ring is usually not encountered (tetralogy of Fallot, truncus arteriosus communis, etc.). The authors never encountered atresia of a segment of the right aortic arch. The last-named was either patent or absent.

Postoperative echocardiographic study of patients following valvulotomy for critical valvular aortic stenosis.

Authors report on long term follow up of 12 patients operated with critical valvular aortic stenosis. They could perform control echocardiography in 11 patients 4-83 (mean 29) months after valvulotomy. The size and function of the left ventricle was found to be satisfactory, with elevated ejection fraction. The cause of the significant pressure gradient between the left ventricle and the aorta is discussed emphasizing the importance of echocardiography in determining the optimal time for valve replacement or homograft implantation.