Bartuś, Krzysztof

Bochenek, Maciej

Ciołczyk-Wierzbicka, Dorota

Drwiła, Rafał

Kapelak, Bogusław

Milaniak, Irena

Przybyłowski, Piotr

Sadowski, Jerzy

Sobczyk, Dorota

Wierzbicki, Karol

Polish Journal of Cardio-Thoracic Surgery

English

Jagiellonian Univeristy Repository

357Kardiochirurgia i Torakochirurgia Polska 2012; 9 (3)NIEWYDOLNOŚĆ SERCA I PŁUC, TRANSPLANTOLOGIAAdres do korespondencji: lek. Maciej Bochenek, ul. Prądnicka 80, 31-202 Kraków, tel. +48 12 614 30 75, +48 12 614 30 72, fax +48 12 423 39 00, Email: bochenekmd@gmail.comAbstractIntroduction: Primary graft failure is a common cause of mor-tality after heart transplantation (HTX). Troponins are widely used as markers of myocardial ischemia, and they appear to be reliable indicators of multifactorial heart transplant injury.Aim of the study: The aim of the present study was to assess the relationship between troponin I levels measured over the first days after HTX and the postoperative clinical course, in-cluding a 6-month follow-up.Material and methods: The retrospective analysis included 54 patients (5 females, 49 males), age 12-62 years (median age 52.0, qr. 15.0) after heart transplantation performed accor ding to the same scheme, in whom the postoperative troponin I levels were measured on several consecutive days after HTX. The relationship between Intensive Care Unit (ICU) length of stay, duration of respiratory therapy and troponin levels was assessed in the patients who survived more than 6 months.Results: There was a positive correlation between the duration of respiratory therapy (median 2.0; qr 1.0) and troponin I levels on several consecutive days after HTX; however, only the relationship on the second postoperative day reached statistical significance. There was also a positive correlation between ICU length of stay (median 7.0, qr 3.0) and troponin I levels. A statistically significant correlation was observed for the troponin I levels on the first, se­cond and third day after HTX. Troponin I levels measured at 0, 2 and 3 days after HTX significantly influenced the survival rate at > 6-month follow-up.Conclusions: Elevated perioperative troponin levels may signi-ficantly influence the clinical course after HTX. Key words: heart transplantation, troponin I, survival.Assessment of the influence of elevated troponin I levels measured in the perioperative period  on the clinical course of patients after heart transplantation in own materialOcena wpływu zwiększonych stężeń troponiny I mierzonej  w okresie okołooperacyjnym na przebieg kliniczny  u chorych po transplantacji serca w materiale własnymKarol Wierzbicki1, Maciej Bochenek1, Dorota Sobczyk1, Irena Milaniak1, Bogusław Kapelak1, Dorota Ciołczyk-Wierzbicka2,  Rafał Drwiła1, Piotr Przybyłowski1, Krzysztof Bartuś1, Jerzy Sadowski11Klinika Chirurgii Serca, Naczyń i Transplantologii Uniwersytetu Jagiellońskiego, Collegium Medicum, Szpital im. Jana Pawła II   w Krakowie 2Katedra Biochemii Lekarskiej Uniwersytetu Jagiellońskiego, Collegium Medicum w KrakowieKardiochirurgia i Torakochirurgia Polska 2012; 3: 357–360StreszczenieWstęp: Pierwotna niewydolność przeszczepu jest częstą przy-czyną zgonów we wczesnym okresie po przeszczepie serca (ang. heart transplantation – HTX). Troponina jako szeroko sto-sowany marker uszkodzenia mięśnia serca wydaje się dobrym wskaźnikiem wieloczynnikowego uszkodzenia także przecze-pionego serca bezpośrednio w okresie okołoperacyjmnym. Cel pracy: Określenie zależności pomiędzy stężeniami tropo-niny I mierzonymi w pierwszych dobach po HTX a przebiegiem klinicznym z uwzględnieniem wczesnej i 6-miesięcznej obser-wacji chorych w materiale własnym.Materiał i metody: Badaniem retrospektywnym objęto 54 cho-rych (5 kobiet, 49 mężczyzn) w wieku 12–62 lat (mediana 52 lata, qr 15,0), u których wykonano przeszczep serca wg identycznego schematu i zmierzono stężenie troponiny I w kolejnych dobach po HTX. Ocenę zależności pomiędzy długością pobytu na Oddziale In-tensywnej Terapii (IT) i czasem respiratototerapii a stężeniami tro-poniny I, przeprowadzono w grupie chorych, którzy przeżyli > 6 mies.Wyniki: Stwierdzono dodatnią korelację pomiędzy czasem re-spi ratoroterapii (mediana 2,0; qr 1,0) a stężeniami troponiny I w kolejnych dobach po HTX, jednak tylko zależność w 2. dobie była istotna statystycznie.Stwierdzono także dodatnią korelację pomiędzy czasem pobytu na Oddziale IT (mediana 7,0; qr 3,0) a stężeniami troponiny I. Istotnie statystyczną zależność stwierdzono pomiędzy stęże-niami troponiny I ocenianymi w 1., 2. i 3. dobie po HTX. Poziom troponiny mierzony w 0., 2. i 3. dobie po HTX istotnie wpływał na przeżycie chorych > 6 miesiąca.Wnioski: Podwyższone poziomy troponiny w okresie okołoope-racyjnym mogą istotnie wpływać na przebieg kliniczny po HTX.DOI: 10.5114/kitp.2012.30849Kardiochirurgia i Torakochirurgia Polska 2012; 9 (3)358Assessment of the influence of elevated troponin I levels measured in the perioperative period on the clinical course...IntroductionHeart transplantation (HTX) is the ultimate treatment option in patients with end-stage heart failure (if other treatments fail) defined as an accepted treatment in the newest ESC (European Society of Cardiology) guidelines. It improves significantly:• survival,• physical capacity,• quality of life [1].The newest ESC guidelines maintain the role of heart transplantation for treatment of end-stage heart failure, but its major limiting factor is still the shortage of donor hearts [1].A half­century has elapsed since the first heart trans-plantation. Long-term transplant survival has improved si-gni ficantly. The ISHLT (International Society for Heart and Lung Transplantation www.ishlt.org) Registry shows a half--life time (the time which 50% of patients survived) of more than 10 years, which is better by about half a year than that after the introduction of cyclosporine in the early 1980s [2].Unfortunately, the number of heart transplants perfor-med each year has not increased and even a reduction has been observed worldwide in recent years. The ISHLT Regi-stry shows that in Europe the number of heart transplants has decreased by over 40% over the last two decades [2]. No doubt this difficult to eliminate scarcity of donor hearts has strengthened the role of mechanical circulatory sup-port according to the ESC guidelines. The use of mechanical circulatory support while waiting for a heart transplant has been assigned to class I recommendations. However, this statement emphasizes in fact the highest clinical value of heart transplantation, which is worth waiting for despite the need for advanced mechanical support [1].Apart from the donor shortage the biggest challenge for the transplant community is a high primary graft failure PGF) rate. PGF is estimated to cause over 40% of all deaths after HTX [3, 4].Troponins are widely used biomarkers of myocardial injury of varying etiology. Theoretically they should be a re-liable indicator of multifactorial heart transplant injury im-mediately after the operation. However, reports on the re-lationship between troponin levels over the first days after HTX and the postoperative course are few [5, 6].Aim of the studyThe purpose of the present study was to assess the re-lationship between troponin I levels measured over the first few days after HTX and the postoperative clinical course, including a 6-month follow-up.Material and methodsThe retrospective analysis included 54 patients (5 F, 49 M), age 12-62 years (median age 52.0, qr. 15.0) after heart trans-plantation.The inclusion criteria in this study were as follows: •  availability of troponin I levels measured over the first days after HTX (from day zero to day 3); troponin I levels were measured using the one-step immunoenzymatic assay (SIEMENS, Germany, normal range from 0.1 ng/ml) (in case of more than one troponin I measurement over 24 hours the highest value was considered in the analysis);•  donor hearts procured using the same standard techni-ques and the same cardioplegic solution CELSIOR in a vo-lume of 4 liters (heart procurement and graft protection have been described elsewhere) [7, 8];•  in order to avoid bias the assessment of the relationship between Intensive Care Unit (ICU) length of stay and du-ration of respiratory therapy and troponin I levels was per-formed in patients who survived > 6 months after HTX.All patients operated on in the Department of Cardiova-scular Surgery and Transplantology, Institute of Cardiology, Jagiellonian University College of Medicine at John Paul II Hospital in Krakow and meeting the inclusion criteria were included in the analysis (changes in the methodology and type of measured troponin were the most important fac-tors limiting the size of the study group).Statistical analysis All statistical analyses were carried out using STATISTICA v.8. The Shapiro-Wilk test for normality was used in the stu-dy. The measurement data which did not meet normal di-stribution were expressed by the median and quartile range (qr). The following tests were used if appropriate:•  Spearman r correlation,•  Mann­Whitney U­test,•  Kruskal­Wallis test.ResultsOver several consecutive days after HTX troponin I le-vels were elevated, reaching 7.6 (median) (minimum) at day 3 (Trop3) and 17.1 (median) (maximum) at day 1 (Trop1), p < 0.0001 (Kruskal-Wallis test) (Tab. I).There was a positive correlation between respiratory therapy duration (median 2 days; qr 1.0) and troponin I le-vels over several consecutive days after HTX. However, the relationship was significant only at day 2 after HTX (Trop2) Tab. I. Troponin I levels over first days after HTX (Trop0 – Day 0, Trop1 – Day 1, Trop2 – Day 2, Trop3 – Day 3) p < 0.0001 (Kruskal-Wallis test)Median qrTrop0 16.9 9.9Trop1 17.1 11.2Trop2 11.6 13Trop3 7.6 8.1Słowa kluczowe: przeszczep serca, troponina I, przeżycie.Kardiochirurgia i Torakochirurgia Polska 2012; 9 (3) 359NIEWYDOLNOŚĆ SERCA I PŁUC, TRANSPLANTOLOGIA(Spearman r correlation) (Tab. II). There was also a positi-ve correlation between ICU length of stay (median 7 days; qr 3.0) and troponin I values. The relationship was signi-ficant at day 1, day 2 and day 3 after HTX (Trop1, Trop2, Trop3) (Spearman r correlation) (Tab. III). Troponin I valu-es measured over several consecutive days after HTX did not significantly affect 30­day survival (7/54 patients died) (p = 0.06; p = 0.2; p = 0.21; p = 0.14, respectively). There was however a significant relationship (positive correla-tion) between troponin I values at day 0, day 2 and day 3 after HTX (Trop0, Trop2, Trop3) and > 6-month survival after HTX (10/54 patients died) (Mann-Whitney U test) (Tab. IV).DiscussionThe donor shortage which limits heart transplants is difficult to eliminate. In 2005 in Poland there were 95 heart transplants in the year, and only 61, 71, 79 and 80 between 2008 and 2011 [9]. This fact automatically forced qualifica-tion for HTX of externally sick patients. For this reason opti-mization of early and long-term outcomes for patients with HTX should be a priority. HTX outcomes have been asses-sed in single and multicenter studies addressing mainly the influence of common complications on survival and quality of life after HTX as well as exploring the most frequent fac-tors limiting the expected medical outcomes in transplant recipients such as primary graft failure, infection, acute and chronic rejection or complications of immunosuppression [10, 11].Troponins are markers of myocardial injury widely used in cardiology and cardiac surgery. Troponin levels are ro-utinely measured at our institution after cardiac surgery. A heart transplantation is associated with many factors that can cause damage to the myocardium; therefore tro-ponin values at different time points after HTX are usually markedly elevated [7, 8, 12]. Troponins, similar to CK­MB isoenzyme, are also almost always determined prior to he-art procurement. However, the role of their elevated levels and most importantly their real effect on “heart transplant capacity” is not yet well understood. Some investigators advise against abstaining from heart procurement in case of high troponin levels if an echocardiogram reveals good cardiac function [13, 14]. There are only a few reports de-fining the effects of high troponin levels on the clinical course in patients after HTX. In our previous study there was no significant effect of troponin I levels measured over Tab. III. Relationship between troponin I levels measured over first days after HTX and Intensive Care Unit (ICU) length of stay (Trop0 – Day 0, Trop1 – Day 1, Trop2 – Day 2, Trop3 – Day 3)ICU length of stayR pTrop0 0.26 0.10Trop1 0.33 0.03*Trop2 0.40 0.01*Trop3 0.39 0.02**Statistical significance (Spearman r correlation).Tab. IV. Relationship between troponin I levels measured over first days after HTX and survival > 6 months (Trop0 – Day 0, Trop1 – Day 1, Trop2 – Day 2, Trop3 – Day 3)Survival > 6 monthsU pTrop0 90.0 0.04*Trop1 140.0 0.10Trop2 93.0 0.03*Trop3 86.0 0.02**Statistical significance (Mann-Whitney U test).Tab. II. Relationship between troponin I levels measured over first days after HTX and respiratory therapy duration (Trop0 – Day 0, Trop1 – Day 1, Trop2 – Day 2, Trop3 – Day 3)Duration of respiratory therapyR pTrop0 0.19 0.22Trop1 0.18 0.26Trop2 0.46 0.003*Trop3 0.31 0.06*Statistical significance (Spearman r correlation).the first few days after HTX on myocardial ischemic inju-ry (biopsy specimen obtained at 10 days after HTX) [15]. In 2000 Labarrere et al. assessed 110 patients undergoing heart transplantation. They found a significantly increased risk of coronary artery disease (vasculopathy) and graft fa-ilure in patients with elevated troponin I levels for one year after HTX [16].In the present study troponin I levels over the first days after HTX had a significant influence on intensive care unit length of stay and respiratory therapy duration. Further-more, troponin I levels measured at day 0, day 2 and day 3 after HTX correlated with > 6-month survival (the higher the level of troponin I the higher the risk of death). Given the paucity of the relevant literature results it is not possi-ble to carry out comparative analyses. However, Amarelli et al. recently reported on a study in which the troponin I values at day 1 after HTX significantly affected the risk of primary graft failure [5].The small sample size does not allow any definitive conclusions. Nevertheless, the present study reveals stati-stically proven effects of troponin I levels measured over the first days after HTX on the clinical course and survival.The current study obtained approval from the Bio-ethics Committee KBET/224/B/2010 and is a part of the K/ZDS/002427 project.References 1. Task Force Members, McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Kardiochirurgia i Torakochirurgia Polska 2012; 9 (3)360Assessment of the influence of elevated troponin I levels measured in the perioperative period on the clinical course...Guidelines (CPG), Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fa-gard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Ten-dera M, Torbicki A, Vahanian A, Windecker S; Document Reviewers, Mc-Donagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiol-ogy. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33: 1787-847.2. www.ishlt.org3. Stehlik J, Edwards LB, Kucheryavaya AY, Aurora P, Christie JD, Kirk R, Dob-bels F, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: twenty­seventh official adult heart trans-plant report – 2010. J Heart Lung Transplant 2010; 29: 1089-1103.4. Young JB, Hauptman PJ, Naftel DC, Ewald G, Aaronson K, Dec GW, Taylor DO, Higgins R, Platt L, Kirklin J. Determinants of early graft failure following car-diac transplantation, a 10-year, multi-institutional, multivariable analysis. J Heart Lung Transplant 2001; 20: 212.5. Amarelli C, De Santo LS, Marra C, Maiello C, Bancone C, Della Corte A, Nappi G, Romano G. Early graft failure after heart transplant: risk factors and impli-cations for improved donor-recipient matching. Interact Cardiovasc Thorac Surg 2012; 15: 57-62.6. Stępień E, Śnieżek­Maciejewska M, Szajna­Zych M, Sadowski J. Biochemiczne markery niedokrwienia mięśnia sercowego w diagnostyce okołooperacyj-nego uszkodzenia serca. Forum Kardiologów 2002; 7: 135-142.7. Wierzbicki K, Sobczyk D, Milaniak I, Bochenek M, Kapelak B, Drwiła R, Wró-bel K, Bartuś K, Ciołczyk­Wierzbicka D, Przybyłowski P, Sadowski J. Influ-ence of the selected factors connected with heart donor on the troponin I levels in the perioperative period after heart transplantation in own mate-rial. Kardiochir Torakochir Pol 2011; 4: 516-520.8. Wierzbicki K, Sobczyk D, Milaniak I, Bochenek M, Piątek J, Drwiła R, Kapelak B, Krupa F, Przybyłowski P, Ciołczyk-Wierzbicka D, Sadowski J. Dynamics of the troponin I levels in the first days after heart transplantation (HTX) in the own material – a pilot study. Kardiochir Torakochir Pol 2011; 3: 379-382.9. Antoszkiewicz K, Czerwiński J. Pobieranie i przeszczepianie narządów w Pol-sce w 2011 r. Poltransplant Biuletyn Informacyjny 2012; 1: 20-33.10. Naftel CD, Brown RN. Survival after heart transplantation. In: Kirklin JK, Young JB, McGiffin DC (eds.). Heart Transplantation. Churchill Livingstone, New York 2002; 587-614. 11. Wróbel K, Przybyłowski P, Wierzbicki K, Sobczyk D, Płatek J, Kapelak B, Mi-laniak I, Sadowski J. Somatic and cardiac status of survivors more than 10 years after heart transplantation in the cyclosporine era. Transplant In-ternational 2005; 18: 81.12. Zimmermann R, Baki S, Dengler TJ, Ring GH, Remppis A, Lange R, Hagl S, Kübler W, Katus HA. Troponin T release after heart transplantation. Br Heart J 1993; 69: 395-398.13.  Guest TM, Ramanathan AV, Tuteur PG, Schechtman KB, Ladenson JH, Jaffe AS. Myocardial injury in critically ill patients. A frequently unreco­gnized complication. JAMA 1995; 273: 1945-1949.14. Kirklin JK, Young JB, McGiffin DC. The donor heart. In: Kirklin JK, Young JB, McGiffin DC (eds.). Heart transplantation. Churchill Livingstone, New York 2002; 193-338.15. Wierzbicki K, Sobczyk D, Milaniak I, Bochenek M, Ciołczyk-Wierzbicka D, Frasik W, Rudnicka-Sosin L, Kapelak B, Drwiła R, Bartuś K, Przybyłowski P, Sadowski J. Ocena zależności pomiędzy stężeniami troponiny I mierzonymi we wczesnym okresie po transplantacji serca a obrazem histopatologicz-nym przeszczepionego serca. Kardiochir Torakochir Pol 2012; 9: 226-230.16. Labarrere CA, Nelson DR, Cox CJ, Pitts D, Kirlin P, Halbrook H. Cardiac-spe-cific troponin I levels and risk of coronary artery disease and graft failure following heart transplantation. JAMA 2000; 284: 457-464.

Ocena wpływu zwiększonych stężeń troponiny I mierzonej w okresie okołooperacyjnym na przebieg kliniczny u chorych po transplantacji serca w materiale własnym

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Ocena wpływu zwiększonych stężeń troponiny I mierzonej w okresie okołooperacyjnym na przebieg kliniczny u chorych po transplantacji serca w materiale własnym

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