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5. Working group on epidemiology & prevention of the european society of cardiology: Proceedings of meeting held at Shannon May 14th–17th, 1998

Author

Sullivan, P. A., Murphy, D., Sullivan, P. A., Keogh, S., Sullivan, P. A., Nash, P., Kaarisalo, M. M., Marttila, J., Immonen-Raiha, P., Salomaa, V., Torppa, J., Tuomilehto, J., Siani, A., Racone, R., Ragone, E., Stinga, F., Strazzullol, P., Cappuccio, F. P., Trevisan, M., Farinaro, E., Mellone, C., Fox, K. F., Cowie, M. R., Wood, D. A., Coats, A. J., Poole Wilson, P. A., Sutton, G. C., Yarnell, J., Sweetnam, P., Thomas, H., Piwonski, J., Piotrowski, W., Pytlak, A., Wannamethee, S. G., Shaper, A. G., Walker, M., Sharpe, P. C., Young, I. S., Hasselwander, O., McMaster, D., Mercer, C., McGrath, L. T., Evans, A. E., Thomas, F., Guize, L., Ducimetiere, P., Benetos, A., Rosolova, H., Simon, J., Mayer, O., Sefrna, F., Mayer, O., Šimon, J., Rosolova, H., Racek, J., Trefil, L., Marin-Tarlea, M., Carp, C., Apetrei, E., Ginghina, C., Serban, I., Florica, N., Ceck, C., Patrascoiu, M., Ginghina, C., Carp, C., Apetrei, E., Tarlea, M., Cioranu, R., Florica, N., Ceck, C., Vaduva, M., Mihaescu, D., Lapadat, M., Ashton, W. D., Wood, D., Nanchahahal, K., Kelleher, C. C., Brennan, P. J., Howarth, D., Meade, T. W., Kelleher, C. C., Fallon, U. B., McCarthy, U., O’Donnell, M. M. K., Dineen, B., Jousilahti, P., Vartiainen, E., Tuomilehto, J., Puska, P., Kastarinen, M., Nissinen, A., Salomaa, V., Vartiainen, E., Jousilahti, P., Tuomilehto, J., Puska, P., Rosengren, A., Wedel, H., Wilhelmsen, L., Liese, A. D., Hense, H. W., Keil, U., Keil, U., Liese, A. D., Hense, H. W., Filipiak, B., Döring, A., Stieber, J., Lowel, H., De Laet, C., Brasseur, D., Kahn, A., Wautrecht, J. C., Decuyper, J., Boeynaems, J. M., Jousilahti, P., Vartiainen, E., Tuomilehto, J., Sundvall, J., Puska, P., Marques-Vidal, P., Ferrières, J., Haas, B., Evans, A., Amouyel, P., Luc, G., Ducimetiere, P., Marques-Vidal, P., Ferrieres, J., Arveiler, D., Montaye, M., Evans, A., Ducimetiere, P., Fuentes, R., Notkola, I. -L., Shemeikka, S., Tuomilehto, J., Nissinen, A., Mak, R., De BacquerBacquer, D., De Backer, G., Stam, M., Koyuncu, R., de Smet, P., Kornitzer, M., Braeckman, L., De Backer, G., De Bacquer, D., Claeys, L., Delanghe, J., De Bacquer, D., Kornitzer, M., De Backer, G., Cífkova, R., Pit’ha, J., Červenka, L., Šejda, T., Lanska, V., Škodová, Z., Stavek, P., Poledne, R., Cífková, R., Duskova, A., Hauserová, G., Hejl, Z., Lánská, V., Škodova, Z., Pistulková, H., Poledne, R., Hubáček, J., Pit’ha, J., Stávek, P., Lánská, V., Cífková, R., Faleiro, L. L., Rodrigues, D., Fonseca, A., Martins, M. C., Norris, R. M., Nyyssönen, K., Seppänen, K., Salonen, R., Kantola, M., Salonen, J. T., Parviainen, M. T., De Henauw, S., Myny, K., Doyen, Z., Van Oyen, H., Tafforeau, J., Kornitzer, M., De Backer, G., Benetos, A., Thomas, F., Guize, L., Immonen-Räihä, P., Kaarisalo, M., Marttila, R. J., Torppa, J., Tuomilehto, J., Houterman, S., Hofman, B., Witteman, J. C. M., Verschuren, W. M. M., van de Vijver, L. P. L., Kardinaal, A. F. M., Grobbee, D. E., van Poppel, G., Princen, H. M. G., Kornitzer, M., Doven, M., Koyuncu, R., De Bacquer, D., Myny, K., De Backer, G., Tafforeau, J., Van Oven, H., Doyen, M., Koyuncu, R., Kornitzer, M., De Bacquer, D., Myny, K., De Backer, G., Tafforeau, J., Van Oyen, H., de Bree, A., Verschuren, W. M. M., Blom, H. J., Mulder, I., Smit, H. A., Menotti, A., Kromhout, D., Van den Hoogen, P. C. W., Hofman, A., Witteman, J. C. M., Feskens, E. J. M., Štika, L., Bruthans, J., Wierzbicka, M., Bolinska, H., Voutilainen, S., Nyyssönen, K., Salonen, R., Lakka, T. A., Salonen, J. T., Lakka, H -M., Lakka, T. A., Salonen, J. T., Tuomainen, T-P., Nyyssonen, K., Salonen, J. T., Punnonen, K., Yarnell, J., Patterson, C., Thomas, H., Sweetnam, P., Smith, W. C. S., Campbell, S. E., Cardy, A., Phillips, D. O., Helms, P. J., Squair, J., Smith, W. C. S., Cardy, A., Phillips, D. O., Helms, P. J., Squair, J., Smith, W. C. S., Cardy, A., Phillips, D. O., Helms, P. J., Squair, J., Pytlak, A., Piotrowski, W., Rywik, S., Waskiewicz, A., Sygnowska, E., Szczesniewska, D., Sygnowska, E., Waskiewicz, A., Wagrowska, H., Polakowska, M., Rywik, S., Broda, G., Jasinski, B., Piotrowski, W., Elandt-Johnson, R. C., Wagrowska, H., Kupsé, W., Szczesniewska, D., Platonov, D. Y., Haapanen, N., Miilunpalo, S., Vuori, I., Pasanen, M., Oja, P., Urponen, H., Kopp, M. S., Skrabski, A., Szedmák, S., Boaz, M., Biro, A., Katzir, Z., Matas, T., Smetana, S., Green, M., Whincup, P. H., Morris, R., Walker, M., Lennon, L., Thomson, A., Ebrahim, S. J. B., Refsum, H., Ueland, P. M., Perry, I. J., Boer, J. M. A., Kuivenhoven, J. A., Feskens, E. J. M., Schouten, E. G., Havekes, L. M., Seidell, J. C., Kastelein, J. J. P., Kromhout, D., Oomen, C. M., Feskens, E. J. M., Rasanen, L., Nissinen, A., Fidanza, F., Menotti, A., Kok, F. J., Kromhout, D., Sileikiene, L., Klambienne, J., Milasauskiene, Z., Cappuccio, F. P., Siani, A., Barba, G., Russo, L., Ragone, E., Strazzullo, P., Farinaro, E., Trevisan, M., Schnohr, P., Parner, J., Lange, P., Meleady, R., Graham, I. M., Ueland, P. M., Refsum, H., Blom, H., Whitehead, A. S., Daly, L. E., Stefanovic, B., Boskovic, D., Mitrovic, P., Perunicic, J., Vukcevic, V., Radovanovic, N., Terzic, B., Mrdovic, I., Orilc, D., Matic, G., Vasiljevic, Z., Mitrovic, P., Boskovic, D., Stefanovic, B., Perunicic, J., Vukcevic, V., Mrdovic, I., Radovanovic, N., Orlic, D., Matic, G., Milentijevic, B., Rajic, D., Mitrovic, N., Boskovic, S., Vasiljevic, Z., Marin-Tarlea, M., Carp, C., Apetrei, E., Serban, I., Ceck, C., Patrascsoiu, M., Florica, N., Mihaescu, D., Murphy, C., Meleady, R., Ingram, S., Love, J., Graham, I., Graham, I. M., Meleady, R., van Berkel, T. F. M., Deckers, J. W., and De Bacquer, D.

Published
1998
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11. Cardiopoietic cell therapy for advanced ischemic heart failure : results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Author

Bartunek, Jozef, Terzic, Andre, Davison, Beth A, Filippatos, Gerasimos S, Radovanovic, Slavica, Beleslin, Branko, Merkely, Bela, Musialek, Piotr, Wojakowski, Wojciech, Andreka, Peter, Horvath, Ivan G, Katz, Amos, Dolatabadi, Dariouch, El Nakadi, Badih, Arandjelovic, Aleksandra, Edes, Istvan, Seferovic, Petar M, Obradovic, Slobodan, Vanderheyden, Marc, Jagic, Nikola, Petrov, Ivo, Atar, Shaul, Halabi, Majdi, Gelev, Valeri L, Shochat, Michael K, Kasprzak, Jaroslaw D, Sanz Ruiz, Ricardo, Heyndrickx, Guy R, Nyolczas, Noémi, Legrand, Victor, Guédès, Antoine, Heyse, Alex, Moccetti, Tiziano, Fernandez Aviles, Francisco, Jimenez Quevedo, Pilar, Bayes Genis, Antoni, Hernandez Garcia, Jose Maria, Ribichini, Flavio, Gruchala, Marcin, Waldman, Scott A, Teerlink, John R, Gersh, Bernard J, Povsic, Thomas J, Henry, Timothy D, Metra, Marco, Hajjar, Roger J, Tendera, Michal, Behfar, Atta, Alexandre, Bertrand, Seron, Aymeric, Stough, Wendy Gattis, Sherman, Warren, Cotter, Gad, Wijns, W. i. l. l. i. a. m. Collaborators Clinical investigators, Dens, sites Belgium: Ziekenhuis Oost Limburg: J., Dupont, M., Mullens, W., Janssens, M., Dolatabadi, Hoˆpital Civil de Charleroi: D., De Bruyne, Y., Lalmand, J., Dubois, P., El Nakadi, B., Aminian, A., De Vuyst, E., Gurnet, P., Gujic, M., Blankoff, I., Guedes, CHU Mont Godinne UCL: A., Gabriel, L., Seldrum, S., Doyen, C., Andre´, M., Heyse, AZ Glorieux: A., Van Durme, F., Verschuere, J., Legrand, Domaine Universitaire du Sart Tilman: V., Gach, O., D’Orio, V., Davin, L., Lancellotti, P., Baudoux, E., Ancion, A., Dulgheru, R., Vanderheyden, OLV Ziekenhuis Aalst – Cardiologie: M., Bartunek, J., Wijns, W., Verstreken, S., Penicka, . M., Gelev, P. Meeus Bulgaria: Tokuda Hospital Sofia: V., Zheleva Kichukova, I., Parapunova, R., Melamed, R., Sardovski, S., Radev, O., Yordanov, A., Radinov, A., Nenov, D., Amine, I., Petrov, City Hospital Clinic Cardiology Center: I., Kichukov, K., Nikitasov, L., Stankov, Z., Stoyanov, H., Tasheva Dimitrova, I., Angelova, M., Dimitrov, E., Minchev, M., Garvanski, I., Botev, C., Polomski, P., Alexandrovska University Hospital, Vassilev, Sofia: D., Karamfiloff, K., Tarnovska Kadreva, R., Vladimirova, L., Dimitrov, G., Hadzhiev, E., Tzvetkova, G., Andreka, . M. Atanasova Hungary: Gottsegen Gyo¨ rgy Orszagos Kardiologiai Inte´zet: P., Fontos, G., Fabian, J., Csepregi, A., Uzonyi, G., Gelei, A., Edes, Debreceni Egyetem Orvos e´s Ege´szse´gtudomanyi Centrum Altalanos Orvostudomanyi Kar Kardiologia Inte´zet: I., Balogh, L., Vajda, G., Darago, A., Gergely, S., Fulop, T., Jenei, C., Horvath, Pe´csi Tudomanyegyetem Klinikai Ko¨zpont Szıvgyogyaszati Klinika: I., Magyari, B., Nagy, A., Cziraki, A., Faludi, R., Kittka, B., Alizadeh, H., Merkely, Semmelweis Egyetem Varosmajori Szıv e´s Ergyogyaszati Klinika: B., Geller, L., Farkas, P., Szombath, G., Foldes, G., Skopal, J., Kovacs, A., Kosztin, A., Gara, E., Sydo, N., Nyolczas, MH Ege´szse´gu¨gyi Ko¨zpont Kardiologiai Osztaly: N., Kerecsen, G., Korda, A., Kiss, . M., Borsanyi, T., Polgar, B., Muk, B., Sharif, Z. Bari Ireland: HRB Clinical Research Facility: F., Atar, Y. M. Smyth Israel:Western Galilee Hospital: S., Shturman, A., Akria, L., Kilimnik, M., Brezins, M., Halabi, Ziv Medical Center: M., Dally, N., Goldberg, A., Aehab, K., Rosenfeld, I., Levinas, T., Saleem, D., Katz, Barzilai Medical Center: A., Plaev, T., Drogenikov, T., Nemetz, A., Barshay, Y., Jafari, J., Orlov, I., Nazareth Hospital EMMS: M. Omory, N. Kogan Nielsen, Shochat, Hillel Yaffe Medical Center: M., Shotan, A., Frimerman, A., Meisel, S., Asif, A., Sofer, O., Blondheim, D. S., Vazan, A., Metra, L. Arobov Italy: A. O. Spedali Civili di Brescia: M., Bonadei, I., Inama, L., Chiari, E., Lombardi, C., Magatelli, M., Russo, D., Lazzarini, V., Carubelli, V., Vassanelli, AOUI Verona – Borgo Trento Hospital: C., Ribichini, Flavio Luciano, Bergamini, C., Krampera, Mauro, Cicoria, M. A., Zanolla, L., Dalla Mura, D., Gambaro, A., Rossi, A., Pesarini Poland: Jagiellonian University Department of Cardiac, G., Musialek, Vascular Diseases at John Paul II Hospital in Krakow: P., Mazurek, A., Drabik, L., Ka˛dzielski, A., Walter, Z., Dzieciuch Rojek, M., Rubis, P., Plazak, . W., Tekieli, L., Podolec, J., Orczyk, W., Sutor, U., Zmudka, K., Olszowska, M., Podolec, P., Gruchala, Uniwersyteckie Centrum Kliniczne: M., Ciecwierz, D., Mielczarek, M., Burakowski, S., Chmielecki, M., Zielinska, M., Frankiewicz, A., Wdowczyk, J., Stopczynska, I., Bellwon, J., Mosakowska, K., Nadolna, R., Wroblewska, J., Rozmyslowska, M., Rynkiewicz, M., Marciniak, I., Raczak, G., Tarnawska, M., Taszner, M., Kasprzak, Bieganski Hospital: J., Plewka, M., Fiutowska, D., Rechcinski, T., Lipiec, P., Sobczak, M., Weijner Mik, P., Wraga, M., Krecki, R., Markiewicz, M., Haval Qawoq, D., Wojakowski, Gornosla˛skie Centrum Medyczne Sla˛skie j. Akademii Medycznej: W., Ciosek, J., Dworowy, S., Gaszewska Zurek, E., Ochala, A., Cybulski, W., Jadczyk, T., Wanha, W., Parma, Z., Kozlowski, M., Dzierzak, M., Markiewicz Serbia: Clinical Hospital Center Zvezdara, M., Arandjelovic, Cardiology Clinic: A., Sekularac, N., Boljevic, D., Bogdanovic, A., Zivkovic, S., Cvetinovic, N., Loncar, G., Clinical Centre of Serbia, Beleslin, Cardiology Clinic: B., Nedeljkovic, M., Trifunovic, D., Giga, V., Banovic, M., Nedeljkovic, I., Stepanovic, J., Vukcevic, V., Djordjevic Dikic, A., Dobric, M., Obrenovic Kircanski, B., Seferovic, Cardiology Clinic: P., Orlic, D., Tesic, M., Petrovic, O., Milinkovic, I., Simeunovic, D., Jagic, Clinical Center of Kragujevac: N., Tasic, M., Nikolic, D., Miloradovic, V., Djurdjevic, P., Sreckovic, M., Zornic, N., Clinical Hospital Center Bezanijska Kosa, Radovanovic, Cardiology Department: S., Saric, J., Hinic, S., Djokovic, A., Ðordevic, S., Bisenic, V., Markovic, O., Stamenkovic, S., Malenkovic, V., Tresnjak, J., Misic, G., Cotra, D., Tomovic, L., Vuckovic, V., Clinic of Emergency Internal Medicine, Obradovic, Military Medical Academy: S., Jovic, Z., Vukotic, S., Markovic, D., Djenic, N., Ristic Andjelkov, A., Bayes Genis, D. Ljubinka Spain: Hospital Universitario Germans Trias I. Pujol: A., Rodriguez Leor, O., Labata, C., Vallejo, N., Ferrer, E., Batlle, M., Fernandez Aviles, Hospital General Universitario Gregorio Mara~non: F., Sanz Ruiz, R., Casado, A., Loughlin, G., Zatarain, E., Anguita, J., Ferna ndez Santos, M. E., Pascual, C., Bermejo, J., Hernandez Garcia, Hospital Clinico Universitario Virgen de la Victoria: J. M., Jimenez Navarro, M., Dominguez, A., Carrasco, F., Mu~noz, A., Garcia Pinilla, J. M., Ruiz, J., Queipo de Llano, M. P., Hernandez, A., Fernandez, A., Jimenez Quevedo, Hospital Clinico San Carlos: P., Guerra, R., Biagioni, C., Gonzalez, R. A., Gomez deDiego, J. J., Mansson Broberg, L. Perez de Isla Sweden: Karolinska University Hospital: A., Sylve´n, C., Leblanc, K., Winter, R., Blomberg, P., Gunyeli, E., Ruck, A., Silva, C., Fo¨rstedt Switzerland: CardioCentro Ticino, J., Moccetti, Switzerland: T., Rossi, M., Pasotti, E., Petrova, I., Crljenica, C., Monti, C., Murzilli, R., Su¨rder, D., Moccetti, M., Turchetto, L., Locicero, V., Chiumiento, L., Maspoli, S., Mombelli, M., Anesini, A., Biggiogero, M., Ponti, G., Camporini, C., Polledri, S., Hill, G. Dolci United Kingdom: Kings College Hospital: J., Plymen, C., Amin Youssef, G., Mcdonagh, T., Drasar, E., Mijovic, A., Jouhra, F., Mcloman, D., Dworakowski, R., Webb, I., Byrne, J., and Potter, V.

Subjects
0301 basic medicine, Male, Cardiopoiesis, Cardiovascular disease, Disease severity, Marker, Precision medicine, Regenerative medicine, Stem cell, Target population, Adult, Aged, Double-Blind Method, Female, Heart Failure, Humans, Mesenchymal Stem Cell Transplantation, Middle Aged, Myocardial Ischemia, Prospective Studies, Treatment Outcome, Young Adult, Cardiology and Cardiovascular Medicine, Cell- and Tissue-Based Therapy, mesenchymal stem-cells, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, outcomes, Fast-Track Clinical Research, Sudden cardiac death, 0302 clinical medicine, Ischemia, cardiovascular disease, Clinical endpoint, target population, CHART Program, Ejection fraction, bone-marrow, Heart Failure/Cardiomyopathy, 3. Good health, Cohort, Cardiology, Fast Track, disease severity, delivery, medicine.medical_specialty, precision medicine, Clinical Sciences, regenerative medicine, 03 medical and health sciences, cardiopoiesis, Internal medicine, medicine, Adverse effect, marker, disease, business.industry, medicine.disease, mortality, Confidence interval, Clinical trial, stem cell, Editor's Choice, 030104 developmental biology, predictors, Cardiovascular System & Hematology, Heart failure, business
Abstract

Altres ajuts: This work was supported by Celyad, SA (Mont-Saint-Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding). Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

Published
2017

12. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study

Author

Patti G, B?rczi G, Orlic D, Mangiacapra F, Colonna G, Pasceri V, Merkely B, Edes I, Ostojic M, Wijns W, Di Sciascio G., BARBATO, EMANUELE, Patti, G, B?rczi, G, Orlic, D, Mangiacapra, F, Colonna, G, Pasceri, V, Barbato, Emanuele, Merkely, B, Edes, I, Ostojic, M, Wijns, W, and Di Sciascio, G.

Published
2011

18. Quantitative evaluation of collateral circulation in patients with previous myocardial infarction: relation to myocardial ischemia, angiographic appearance and functional improvement of myocardium.

Author

Vukcevic V, Beleslin B, Ostojic M, Stojkovic S, Stankovic G, Nedeljkovic M, Orlic D, Djordjevic-Dikic A, Stepanovic J, Giga V, Arandjelovic A, Dikic M, Kostic J, Nedeljkovic I, Nedeljkovic-Beleslin B, Saponjski J, Vukcevic, Vladan, Beleslin, Branko, Ostojic, Miodrag, and Stojkovic, Sinisa

Abstract

Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts (mean age 53 +/- 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty. Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P(w)) and aortic pressure (P(a)). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional improvement of myocardium in the follow-up period. Mean P(w)/P(a) was 0.24 +/- 0.10 (range of 0.07-0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients (35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed (r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P(w)/P(a) was significantly higher in comparison to patients with ECG changes (0.28 +/- 0.09 vs. 0.15 +/- 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P(w)/P(a) was significantly higher than in the patients without echo improvement (0.26 +/- 0.10 vs. 0.18 +/- 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals. Low values of P(w)/P(a) are associated with ECG changes during balloon occlusion. Higher P(w)/P(a) was associated with better functional improvement of myocardium. [ABSTRACT FROM AUTHOR]

Published
2009
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20. Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells.

Author

Bunnell, B A, Kluge, K A, Lee-Lin, S-Q, Byrne, E R, Orlic, D, Metzger, M E, Agricola, B A, Wersto, R P, Bodine, D M, Morgan, R A, and Donahue, R E

Subjects
CELL transplantation, GENETIC transduction, GIBBONS, LEUKEMIA
Abstract

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony- forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34+ cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50000/μl and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 × 107 or greater of cytokine-mobilized CD34+ PB cells/kg. Reverse transcriptase(RT)-PCR analysis of CD34+ subsets for both the GaLV and amphotropic receptor were performed. The expression of the GaLV receptor was determined to be restricted to CD34+ Thy-1+ cells, and both CD34+ CD38+ and CD34+ CD38dim cells, while the amphotropic receptor was present on all CD34+ cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34+ cells as only CD34+Thy-1+ cells express the GaLV receptor. [ABSTRACT FROM AUTHOR]

Published
1999
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21. The radiological appearance of appositional new bone on the medial part of the neck of the femur in coxarthrosis.

Author

Orlic, D. and Ruszkowski, I.

Subjects
BONE growth, FEMUR neck, HIP joint, LONGITUDINAL method, OSTEOARTHRITIS, RADIOGRAPHY
Abstract

Copyright of International Orthopaedics is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
1983
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24. Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Results From the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Randomized Study

Author

Patti, G, Barczi, G, Orlic, D, Mangiacapra, F, Colonna, G, Pasceri, V, Barbato, E, Merkely, B, Edes, I, Ostojic, M, Wijns, W, and Di Sciascio, G

Subjects
clopidogrel, percutaneous coronary intervention, outcome, acute myocardial infarction, infarct size, cardiovascular diseases
Abstract

ObjectivesThe purpose of this study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarction (STEMI).BackgroundGiven the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study.MethodsA total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n = 103) or 300-mg (n = 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers.ResultsInfarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p = 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p < 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade

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26. Presence of early endothelial cells in aspirated coronary thrombi from patients with ST-elevation myocardial infarction - their association with angiographic outcomes.

Author

Kostic, J., Orlic, D., Stankovic, G., Popovic, D., Bajcetic, M., Puka, N., Zaletel, I., Zlatic, N., and Labudovic-Borovic, M.

Subjects
*CORONARY disease, *CORONARY angiography, *ELECTROCARDIOGRAPHY, *ENDOTHELIAL cells, *HEALTH outcome assessment, MYOCARDIAL infarction diagnosis
Published
2015
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27. P520 Percutaneous coronary intervention for chronic total occlusions of coronary arteries: procedural characteristics and long-term clinical outcomes.

Author

Jeremic, V, Stojkovic, S, Dobric, M, Vukcevic, V, Orlic, D, Cvorovic, I, and Vasiljevic-Pokrajcic, Z

Subjects
ANGIOPLASTY, ARTERIAL occlusions, ANGINA pectoris, CHEST pain, HEALTH outcome assessment, MEDICAL statistics
Abstract

Purpose: Despite the fact that techniques for recanalization of chronic total occlusions (CTO) are improved, the benefit of successful recanalization of the artery remains unclear. The aim of our study is to determine the success rate of percutaneous procedures and to evaluate the event free long-term survival in patients with CTO who underwent percutaneous coronary intervention (PCI).Methods: Our study included 283 consecutive patients with chronic total occlusions who underwent percutaneous coronary intervention on CTO at Clinic for Cardiology, between Jan 1st 2009 and Dec 31st 2010. Data were obtained retrospectively from Cath lab database at Clinic for Cardiology. Follow up data were obtained by direct phone contact.Results: Overall procedural success was achieved in 62.3% interventions. Independent predictors for procedural failure were presence of vessel tortuosity (P=0.007), vessel wall calcifications (P=0.000), blunt stump (P=0.000) and unstable angina pectoris as negative predictor (P=0.009). Overall MACE rates were similar in the procedural success and procedural failure groups (10% vs. 12.8%, p=0.455). There was no significant difference in the event free survival rate between success and failure group (89.8% vs. 87.2%, Log-Rank =0.468, p=0.494).Conclusions: Our study demonstrated that success rate of PCI in patients with CTO is acceptable and safe. Nevertheless, successful recanalization of CTO was not associated with an improved event free survival. [ABSTRACT FROM AUTHOR]

Published
2014
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28. 221 Chronotropic incompetence vs. echocardiographic ischemia as a predictor of repeat revascularization after the first coronary intervention on left anterior descending coronary artery

Author

Orlic, D., Ostojic, M., Djordjevic-Dikic, A., Stepanovic, J., Beleslin, B., Stankovic, G., Saponjski, J., and Vukcevic, V.

Abstract

An abstract of the article "Chronotropic incompetence vs. echocardiographic ischemia as a predictor of repeat revascularization after the first coronary intervention on left anterior descending coronary artery," by D. Orlic and colleagues is presented.

Published
2006
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30. Antiplatelet effect of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an analysis of the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Study

Author

Emanuele Barbato, Fabio Mangiacapra, Dejan Orlic, Germano Di Sciascio, William Wijns, Miodrag Ostojic, Giuseppe Patti, Andrea D'Ambrosio, Aaron Peace, Mangiacapra, F, Patti, G, Barbato, Emanuele, Orlic, D, Peace, Aj, D'Ambrosio, A, Ostojic, M, Wijns, W, and Di Sciascio, G.

Subjects
medicine.medical_specialty, Internationality, Ticlopidine, medicine.medical_treatment, Myocardial Infarction, Infarction, Percutaneous Coronary Intervention, Postoperative Complications, Internal medicine, Angioplasty, medicine, Humans, ST segment, In patient, Prospective Studies, Myocardial infarction, Angioplasty, Balloon, Coronary, Dose-Response Relationship, Drug, business.industry, Medical school, Percutaneous coronary intervention, medicine.disease, Clopidogrel, humanities, Treatment Outcome, Cardiology, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract

undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an analysis of the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Study Fabio Mangiacapra ⁎, Giuseppe Patti , Emanuele Barbato , Dejan Orlic , Aaron J. Peace , Andrea D'Ambrosio , Miodrag Ostojic , William Wijns , Germano Di Sciascio a,⁎,1 a Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy b Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium c Department of Diagnostics and Catheterization Laboratories, Division of Cardiology, Clinical Center of Serbia, Medical School of Belgrade, Belgrade, Serbia

Published
2012

33. Successful Caesarean Section on Ticagrelor Treatment One Day after Primary Percutaneous Coronary Intervention.

Author

Antonijevic N, Mitrovic P, Gosnjic N, Orlic D, Kadija S, Ilic Mostic T, Savic N, Birovljev L, Lekovic Z, and Matic D

Abstract

Caesarean section is a challenging intervention in patients treated with dual antiplatelet therapy. We present a case of a 32-year-old pregnant woman experiencing large acute myocardial infarction (MI) of the anterolateral wall, complicated by cardiogenic shock in the 38th week of pregnancy, and treated with drug-eluting stent implantation and dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor. Less than 24 h after the MI delivery started, an urgent Caesarean section was indicated. As multiplate aggregometry testing showed a relatively insufficient level of ticagrelor platelet inhibition and a moderate level of aspirin platelet inhibition, a Caesarean section was performed without discontinuation of ticagrelor, which was decided due to the need for emergency surgery. Local hemostatic measures including administration of tranexamic acid were applied. The patient did not experience excessive bleeding. A healthy male baby was born. To the best of our knowledge, this is the first reported case of surgery in pregnant women treated with DAPT without ticagrelor discontinuation.

Published
2023
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34. Case report: Acute toxic myocardial damage caused by 5-fluorouracil-from enigma to success.

Author

Lasica R, Spasic J, Djukanovic L, Trifunovic-Zamaklar D, Orlic D, Nedeljkovic-Arsenovic O, and Asanin M

Abstract

Considering the pandemic of both cardiovascular diseases and oncological diseases, there is an increasing need for the use of chemotherapy, which through various pathophysiological mechanisms leads to damage to heart function. Cardio toxicity of chemotherapy drugs can manifest itself in a variety of clinical manifestations, which is why establishing a valid diagnosis is a real mystery for clinicians. Acute systolic heart failure (AHF) due to the use of 5-fluorouracil (5-FU) is a rare occurrence if it is not associated with myocardial infarction, myocarditis or Takotsubo cardiomyopathy. Therefore, we decided to present a case of an 52-year-old male who was diagnosed with stage IV RAS wild-type adenocarcinoma of the rectum and in whom the direct toxic effect 5-FU is the main reason for the appearance of toxic cardiomyopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lasica, Spasic, Djukanovic, Trifunovic-Zamaklar, Orlic, Nedeljkovic-Arsenovic and Asanin.)

Published
2022
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35. Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients With Asymmetric Hypertrophic Cardiomyopathy.

Author

Tesic M, Beleslin B, Giga V, Jovanovic I, Marinkovic J, Trifunovic D, Petrovic O, Dobric M, Aleksandric S, Juricic S, Boskovic N, Tomasevic M, Ristic A, Orlic D, Stojkovic S, Vukcevic V, Stankovic G, Ostojic M, and Djordjevic Dikic A

Subjects
Adult, Blood Flow Velocity, Female, Humans, Male, Middle Aged, Prognosis, Cardiomyopathy, Hypertrophic diagnostic imaging, Cardiomyopathy, Hypertrophic physiopathology, Echocardiography, Doppler
Abstract

Background Microvascular dysfunction might be a major determinant of clinical deterioration and outcome in patients with hypertrophic cardiomyopathy (HCM). However, long-term prognostic value of transthoracic Doppler echocardiography (TDE) coronary flow velocity reserve (CFVR) on clinical outcome is uncertain in HCM patients. Therefore, the aim of our study was to assess long-term prognostic value of CFVR on clinical outcome in HCM population. Methods and Results We prospectively included 150 HCM patients (82 women; mean age 48±15 years). Patients' clinical characteristics, echocardiographic and CFVR findings (both for left anterior descending [LAD] and posterior descending artery [PD]), were assessed in all patients. The primary outcome was a composite of: HCM related death, heart failure requiring hospitalization, sustained ventricular tachycardia and ischemic stroke. Patients were stratified into 2 subgroups depending on CFVR LAD value: Group 1 (CFVR LAD>2, [n=87]) and Group 2 (CFVR LAD≤2, [n=63]). During a median follow-up of 88 months, 41/150 (27.3%) patients had adverse cardiac events. In Group 1, there were 8/87 (9.2%), whereas in Group 2 there were 33/63 (52.4%, P <0.001 vs. Group 1) adverse cardiac events. By Kaplan-Meier analysis, patients with preserved CFVR LAD had significantly higher cumulative event-free survival rate compared to patients with impaired CFVR LAD (96.4% and 90.9% versus 66.9% and 40.0%, at 5 and 8 years, respectively: log-rank 37.2, P <0.001). Multivariable analysis identified only CFVR LAD≤2 as an independent predictor for adverse cardiac outcome (HR 6.54; 95% CI 2.83-16.30, P <0.001), while CFVR PD was not significantly associated with outcome. Conclusions In patients with HCM, impaired CFVR LAD (≤2) is a strong, independent predictor of adverse cardiac outcome. When the aim of testing is HCM risk stratification and CFVR LAD data are available, the evaluation of CFVR PD is redundant.

Published
2021
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36. Prompt and consistent improvement of coronary flow velocity reserve following successful recanalization of the coronary chronic total occlusion in patients with viable myocardium.

Author

Dobric M, Beleslin B, Tesic M, Djordjevic Dikic A, Stojkovic S, Giga V, Tomasevic M, Jovanovic I, Petrovic O, Rakocevic J, Boskovic N, Sobic Saranovic D, Stankovic G, Vukcevic V, Orlic D, Simic D, Nedeljkovic MA, Aleksandric S, Juricic S, and Ostojic M

Subjects
Chronic Disease, Coronary Occlusion diagnosis, Coronary Occlusion physiopathology, Coronary Vessels diagnostic imaging, Coronary Vessels surgery, Echocardiography, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Time Factors, Coronary Occlusion surgery, Coronary Vessels physiopathology, Fractional Flow Reserve, Myocardial physiology, Myocardial Contraction physiology, Percutaneous Coronary Intervention
Abstract

Background: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO., Methods: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO., Results: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS)., Conclusions: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months., Trial Registration: ClinicalTrials.gov (Number NCT04060615 ).

Published
2020
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37. Impairment of coronary flow velocity reserve and global longitudinal strain in women with cardiac syndrome X and slow coronary flow.

Author

Jovanovic I, Tesic M, Giga V, Dobric M, Boskovic N, Vratonjic J, Orlic D, Gudelj O, Tomasevic M, Dikic M, Nedeljkovic I, Trifunovic D, Nedeljkovic MA, Dedic S, Beleslin B, and Djordjevic-Dikic A

Subjects
Aged, Blood Flow Velocity, Coronary Circulation, Coronary Vessels physiopathology, Female, Humans, Middle Aged, Ventricular Function, Left, Microvascular Angina physiopathology
Abstract

Background: Microvascular dysfunction (MVD) is associated with adverse prognosis and may account for abnormal stress tests and angina symptoms in women with cardiac syndrome X (CSX). The aim of our study was to assess MVD by coronary flow velocity reserve (CFVR) and left ventricular (LV) contractile function by LV global longitudinal strain (LVGLS) in CSX patients with respect to presence of slow coronary flow (SCF). It was of additional importance to evaluate clinical status of CSX patients using Seattle Angina Questionnaire., Methods and Results: Study population included 70 women with CSX (mean age 61 ± 7 years) and 34 age-matched controls. CSX group was stratified into two subgroups depending on SCF presence: CSX-Thrombolysis In Myocardial Infarction (TIMI) 3- normal flow subgroup (n = 38) and CSX-TIMI 2- SCF subgroup (n = 32) as defined by coronary angiography. LVGLS measurements and CFVR of left anterior descending (LAD) and posterior descending (PD) artery were performed. CFVR-LAD and PD were markedly impaired in CSX group compared to controls (2.34 ± 0.25 vs 3.05 ± 0.21, p < 0.001; 2.32 ± 0.24 vs 3.01 ± 0.13, p < 0.001), and furthermore decreased in CSX-TIMI 2 patients. Resting, peak, and ΔLVGLS were all significantly impaired in CSX group compared to controls (for all p < 0.001), and furthermore reduced in CSX-TIMI 2 subgroup. Strongest correlation was found between peak LVGLS and CFVR LAD (r = -0.784, p < 0.001) and PD (r = -0.772, p < 0.001). CSX-TIMI 2 subgroup had more frequent angina symptoms and more impaired quality of life., Conclusions: MVD in CSX patients is demonstrated by reduction in CFVR and LVGLS values. SCF implies more profound impairment of microvascular and LV systolic function along with worse clinical presentation., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Published
2020
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38. Prognostic Value of Transthoracic Doppler Echocardiography Coronary Flow Velocity Reserve in Patients with Nonculprit Stenosis of Intermediate Severity Early after Primary Percutaneous Coronary Intervention.

Author

Tesic M, Djordjevic-Dikic A, Giga V, Stepanovic J, Dobric M, Jovanovic I, Petrovic M, Mehmedbegovic Z, Milasinovic D, Dedovic V, Zivkovic M, Juricic S, Orlic D, Stojkovic S, Vukcevic V, Stankovic G, Nedeljkovic M, Ostojic M, and Beleslin B

Subjects
Coronary Stenosis mortality, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Prospective Studies, ST Elevation Myocardial Infarction mortality, Severity of Illness Index, Survival Rate, Coronary Stenosis diagnostic imaging, Coronary Stenosis surgery, Echocardiography, Doppler, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction diagnostic imaging, ST Elevation Myocardial Infarction surgery
Abstract

Background: Treatment of nonculprit coronary stenosis during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction may be beneficial, but the mode and timing of the intervention are still controversial. The aim of this study was to examine the significance and prognostic value of preserved coronary flow velocity reserve (CFVR) in patients with nonculprit intermediate stenosis early after primary percutaneous coronary intervention., Methods: Two hundred thirty patients with remaining intermediate (50%-70%) stenosis of non-infarct-related arteries, in whom CFVR was performed within 7 days after primary percutaneous coronary intervention, were prospectively enrolled. Twenty patients with reduced CFVR and positive results on stress echocardiography or impaired fractional flow reserve underwent revascularization and were not included in further analysis. The final study population of 210 patients (mean age, 58 ± 10 years; 162 men) was divided into two groups on the basis of CFVR: group 1, CFVR > 2 (n = 174), and group 2, CFVR ≤ 2 (n = 36). Cardiac death, nonfatal myocardial infarction, and revascularization of the evaluated vessel were considered adverse events., Results: Mean follow-up duration was 47 ± 16 months. Mean CFVR for the whole group was 2.36 ± 0.40. There were six adverse events (3.4%) related to the nonculprit coronary artery in group 1, including one cardiac death, one ST-segment elevation myocardial infarction, and four revascularizations. In group 2, there were 30 adverse events (83.3%, P < .001 vs group 1), including two cardiac deaths, two ST-segment elevation myocardial infarctions, and 26 revascularizations., Conclusions: In patients with CFVR > 2 of the intermediate nonculprit coronary lesion, deferral of revascularization is safe and associated with excellent long-term clinical outcomes., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Published
2018
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39. Improved Propensity-Score Matched Long-Term Clinical Outcomes in Patients with Successful Percutaneous Coronary Interventions of Coronary Chronic Total Occlusion.

Author

Stojkovic S, Juricic S, Dobric M, Nedeljkovic MA, Vukcevic V, Orlic D, Stankovic G, Tomasevic M, Aleksandric S, Dikic M, Tesic M, Mehmedbegovic Z, Boskovic N, Zivkovic M, Dedovic V, Milasinovic D, Ostojic M, and Beleslin B

Subjects
Aged, Female, Humans, Incidence, Male, Middle Aged, Patient Outcome Assessment, Percutaneous Coronary Intervention methods, Propensity Score, Registries, Risk Factors, Serbia epidemiology, Coronary Occlusion diagnosis, Coronary Occlusion mortality, Coronary Occlusion surgery, Long Term Adverse Effects diagnosis, Long Term Adverse Effects epidemiology, Long Term Adverse Effects etiology, Percutaneous Coronary Intervention adverse effects
Abstract

The objective of the study was to evaluate major adverse cardiovascular events (MACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Limited data are available on long-term clinical follow-up in the treatment of chronic total occlusion (CTO).Between January 2009 and December 2010 PCI-CTO was attempted in 283 consecutive patients with 289 CTO lesions. Procedural success was 62.3% and clinical follow-up covered 83% (235/283) of the study population with a median follow-up of 66 months (range, 59-74).The total incidence of MACE was 57/235 (24.3%), and was significantly higher in the procedural failure group than in the procedural success group (33/87 (37.9%) versus 24/148 (16.2%), P < 0.001). All-cause mortality was significantly lower in patients with successful PCI-CTO compared to failed PCI-CTO (10.8% versus 20.7%, P < 0.05). Also, the rate of cardiovascular death in the procedural failure group (14.9%) was slightly higher than that in the procedural success group (7.4%, P = 0.066). The rate of TVR was statistically higher in the procedural failure group (P < 0.009). Propensity score-adjusted Cox regression showed that procedural success remained a significant predictor of MACE (adjusted HR 0.402; 95% CI 0.196-0.824; P = 0.013).Our study emphasizes the importance of CTO recanalization in improving long-term outcome including all-cause mortality with a borderline effect on cardiovascular mortality.

Published
2018
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40. Endothelial cell markers from clinician's perspective.

Author

Rakocevic J, Orlic D, Mitrovic-Ajtic O, Tomasevic M, Dobric M, Zlatic N, Milasinovic D, Stankovic G, Ostojić M, and Labudovic-Borovic M

Subjects
Antigens, CD34 genetics, Antigens, CD34 metabolism, Cardiovascular Diseases diagnosis, Endoglin genetics, Endoglin metabolism, Humans, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Randomized Controlled Trials as Topic, Receptors, Vascular Endothelial Growth Factor genetics, Receptors, Vascular Endothelial Growth Factor metabolism, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-3 genetics, Vascular Endothelial Growth Factor Receptor-3 metabolism, von Willebrand Factor genetics, von Willebrand Factor metabolism, Biomarkers, Cardiovascular Diseases genetics, Endothelial Cells metabolism
Abstract

Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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41. Co-expression of vascular and lymphatic endothelial cell markers on early endothelial cells present in aspirated coronary thrombi from patients with ST-elevation myocardial infarction.

Author

Rakocevic J, Kojic S, Orlic D, Stankovic G, Ostojic M, Petrovic O, Zaletel I, Puskas N, Todorovic V, and Labudovic-Borovic M

Subjects
Biomarkers analysis, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors blood, Myocardial Infarction pathology, Neovascularization, Pathologic metabolism, Thrombosis metabolism, Antigens, CD34 metabolism, Endothelial Cells metabolism, Myocardial Infarction metabolism, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Vascular Endothelial Growth Factor Receptor-3 metabolism, Vesicular Transport Proteins metabolism
Abstract

Introduction: Angiogenesis is the growth of both new vascular and lymphatic blood vessels from the existing vasculature. During this process, blood endothelial cells (BECs) and lymphatic endothelial cells (LECs) express specific markers, which help their discrimination and easier identification. Since the coronary thrombi material aspirated from patients with ST-elevation myocardial infarction (STEMI) proved as good angiogenesis model, we investigated the expression of CD34 and CD31 as BECs markers, and D2-40, LYVE-1 and VEGFR3 as LEC markers in this material., Materials and Methods: Aspirated thrombi were stained immunohistochemically for CD34, CD31, D2-40, LYVE-1 and VEGFR3. Organizational patterns of immunopositive cells were graded as single cells, clusters or microvessels. Double immunofluorescence for CD31, D2-40, LYVE-1 and VEGRF3 was done. Thrombi were also graded as fresh (<1day old), lytic (1-5days old) and organized (>5days old)., Results: Serial sections of aspirated thrombi showed concordant BEC and LEC markers immunopositivity. Double immunoflorescence proved co-expression of CD31 and LEC markers on the same cells. Cells expressing LEC markers organized in clusters and microvessels were mainly present in lytic and organized thrombi., Conclusion: Co-expression of BEC and LEC markers on the same non-tumorous cell during thrombus neovascularization indicates existing in vivo plasticity of endothelial cells under non-tumorous pathological conditions. It also points that CD34 and CD31 on one hand, and D2-40, LYVE-1 and VEGFR3 immunostaining on the other hand, cannot solely be a reliable indicators whether vessel is lymphatic or not., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2016
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42. B-type Natriuretic Peptide and RISK-PCI Score in the Risk Assessment in Patients with STEMI Treated by Primary Percutaneous Coronary Intervention.

Author

Asanin M, Mrdovic I, Savic L, Matic D, Krljanac G, Vukcevic V, Orlic D, Stankovic G, Marinkovic J, and Stankovic S

Subjects
Adult, Aged, Electrocardiography, Female, Humans, Male, Middle Aged, Myocardial Infarction therapy, ROC Curve, Myocardial Infarction mortality, Natriuretic Peptide, Brain blood, Percutaneous Coronary Intervention, Risk Assessment
Abstract

Background: RISK-PCI score is a novel score for risk stratification of patients with ST elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). The aim of this study was to evaluate the role of B-type natriuretic peptide (BNP) and the RISK-PCI score for early risk assessment in patients with STEMI treated by pPCI., Methods: In 120 patients with STEMI treated by pPCI, BNP was measured on admission before pPCI. The primary end point was 30-day mortality., Results: The ROC curve analysis revealed that the most powerful predictive factors of 30-day mortality were the plasma level of BNP ≥ 206.6 pg/mL with the sensitivity of 75% and specificity of 87.5% and the RISK-PCI score ≥ 5.25 with the sensitivity of 75% and specificity of 85.7%. Thirty-day mortality was 6.7%. After multivariate adjustment, admission BNP (≥ 206.6 pg/mL) (OR 2.952, 95% CI 1.072 - 8.133, p = 0.036) and the RISK-PCI score (≥ 5.25) (OR 2.284, 95% CI 1.140-4.578, p = 0.020) were independent predictors of 30-day mortality. The area under the ROC curve using the RISK-PCI score and BNP to detect mortality was 0.828 (p = 0.002) and 0.903 (p < 0.001), respectively. Addition of BNP to RISK-PCI score increased the area under the ROC to 0.949 (p < 0.001), but this increase measured by the c-statistic was not significant (p = 0.107). Furthermore, the significant improvement in risk reclassification (p < 0.001) and the integrated discrimination index (p = 0.042) were observed with the addition of BNP to RISK-PCI score for 30-day mortality., Conclusions: BNP on admission and the RISK-PCI score were the independent predictors of 30-day mortality in patients with the STEMI treated by pPCI. BNP in combination with the RISK-PCI score showed the way to more accurate risk assessment in patients with STEMI treated by pPCI.

Published
2016
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43. Epidemiology of musculoskeletal tumors in a national referral orthopedic department. A study of 3482 cases.

Author

Bergovec M, Kubat O, Smerdelj M, Seiwerth S, Bonevski A, and Orlic D

Subjects
Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Incidence, Infant, Male, Middle Aged, Retrospective Studies, Sex Distribution, Young Adult, Bone Neoplasms epidemiology, Neoplasms, Connective and Soft Tissue epidemiology
Abstract

Aim of the Study: Musculoskeletal tumors are relatively rare, and their geographic distribution varies greatly around the world. In this study, we present the incidence, age distribution and localization of musculoskeletal tumors diagnosed and/or treated at a tertiary referral orthopedic department, catering to an entire Southeastern European country., Methods: This was a retrospective study of prospectively collected data, in which all patients diagnosed and/or treated for musculoskeletal tumors at our Department in the period of 30 years (1981-2010) were included., Results: Data of a total of 3482 patients with musculoskeletal tumors were collected. Average age of patients was 33.5 years (range, 2 months-88 years), with even distribution according to sex. Malignant tumors were seen in 20.7% of patients, more often in men (56.9%). Most common malignant tumors were osteosarcoma (estimated incidence: 1.68/million/year), chondrosarcoma (0.79/million/year) and Ewing sarcoma (0.76/million/year). Benign tumors and tumor-like lesions were found in 79.3% of patients, with slight female predominance. Most common benign bone lesions were osteochondroma (5.81/million/year), simple bone cyst (2.13/million/year), and enchondroma (2.05/million/year)., Conclusion: This report represents a first of its kind in our region, and gives representative results to be compared to other middle and south European countries. Further nationwide studies are needed to improve strategies in bone tumor diagnosis and treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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44. Time-dependent changes of plasma adiponectin concentration in relation to coronary microcirculatory function in patients with acute myocardial infarction treated by primary percutaneous coronary intervention.

Author

Trifunovic D, Stankovic S, Marinkovic J, Beleslin B, Banovic M, Djukanovic N, Orlic D, Tesic M, Vujisic-Tesic B, Petrovic M, Nedeljkovic I, Stepanovic J, Djordjevic-Dikic A, Giga V, and Ostojic M

Subjects
Aged, Female, Humans, Male, Middle Aged, Myocardial Infarction blood, Odds Ratio, Time Factors, Adiponectin blood, Coronary Circulation, Microcirculation, Myocardial Infarction therapy, Percutaneous Coronary Intervention adverse effects
Abstract

Background and Purpose: To analyze plasma adiponectin kinetics in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) and its association with coronary flow reserve (CFR), an index of coronary microcirculatory function., Methods: A total of 96 consecutive patients with the first anterior STEMI treated by pPCI without heart failure were included. CFR was assessed on the 7th day after pPCI. Plasma adiponectin was measured on admission before pPCI, and on the 2nd and 7th day after pPCI., Results: Adiponectin concentration was the highest on admission, declined to the lowest level on the 2nd day, and rose on the 7th day remaining below admission values. Impaired coronary microcirculatory function (CFR<2) was observed in 41% of the patients. Adiponectin concentrations significantly positively correlated with CFR, and the strongest correlation was with the 2nd day adiponectin (r=0.489, p<0.001). In multivariate models, adiponectin concentrations were independent predictors of impaired CFR [on admission: odds ratio (OR) 0.175, confidence interval (CI): 0.047-0.654, p=0.010; 2nd day: OR 0.146, 95% CI: 0.044-0.485, p=0.002; 7th day: OR 0.198, CI: 0.064-0.611, p=0.005]. The best power to predict impaired CFR was the 2nd day adiponectin. Delta values of adiponectin (differences between adiponectin concentrations) did not correlate with CFR., Conclusions: In patients with the first anterior STEMI treated by pPCI plasma adiponectin concentrations before and after pPCI are strongly associated with CFR. Our results support the hypothesis that low adiponectin, especially during the early post-pPCI period, carries the risk for impaired coronary microcirculatory function in STEMI patients., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Published
2015
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45. Reduced sirolimus systemic exposure and improved bioresorbable polymer properties: new allies for the treatment of patients with coronary artery disease.

Author

Stojkovic S, Neskovic AN, Mehmedbegovic Z, Kafedzic S, Ostojic M, Nedeljkovic M, Orlic D, Ilisic B, Ilic I, Aleksic A, Cerovic M, Nikolajevic I, Vlahovic-Stipac A, Stajic Z, Putnikovic B, and Hamilos M

Subjects
Adult, Aged, Angioplasty, Balloon, Coronary methods, Coronary Angiography methods, Coronary Artery Disease blood, Drug-Eluting Stents adverse effects, Female, Humans, Male, Middle Aged, Polymers adverse effects, Prospective Studies, Sirolimus adverse effects, Sirolimus blood, Treatment Outcome, Coronary Artery Disease drug therapy, Polymers metabolism, Sirolimus pharmacokinetics
Abstract

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity., (© 2014 Société Française de Pharmacologie et de Thérapeutique.)

Published
2015
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46. Coronary flow of the infarct artery assessed by transthoracic Doppler after primary percutaneous coronary intervention predicts final infarct size.

Author

Trifunovic D, Sobic-Saranovic D, Beleslin B, Stankovic S, Marinkovic J, Orlic D, Vujisic-Tesic B, Petrovic M, Nedeljkovic I, Banovic M, Djukanovic N, Petrovic O, Petrovic M, Stepanovic J, Djordjevic-Dikic A, Tesic M, and Ostojic M

Subjects
Adenosine, Aged, Biomarkers blood, Blood Flow Velocity, Coronary Vessels physiopathology, Creatine Kinase, MB Form blood, Feasibility Studies, Female, Humans, Male, Microcirculation, Middle Aged, Multivariate Analysis, Myocardial Infarction blood, Myocardial Infarction diagnostic imaging, Myocardial Infarction physiopathology, Myocardial Perfusion Imaging methods, Predictive Value of Tests, Prospective Studies, Serbia, Time Factors, Tomography, Emission-Computed, Single-Photon, Treatment Outcome, Vasodilator Agents, Coronary Vessels diagnostic imaging, Echocardiography, Doppler, Fractional Flow Reserve, Myocardial, Myocardial Infarction therapy, Percutaneous Coronary Intervention
Abstract

Coronary microcirculatory function after primary percutaneous coronary intervention (pPCI) in patients with acute myocardial infarction is important determinant of infarct size (IS). Our aim was to investigate the utility of coronary flow reserve (CFR) and diastolic deceleration time (DDT) of the infarct artery (IRA) assessed by transthoracic Doppler echocardiography after pPCI for final IS prediction. In 59 patients, on the 2nd day after pPCI for acute anterior myocardial infarction, transthoracic Doppler analysis of IRA blood flow was done including measurements of CFR, baseline DDT and DDT during adenosine infusion (DDT adeno). Killip class, myocardial blush grade, resolution of ST segment elevation, peak creatine kinase-myocardial band and conventional echocardiographic parameters were determined. Single-photon emission computed tomography myocardial perfusion imaging was done 6 weeks later to define final IS (percentage of myocardium with fixed perfusion abnormality). IS significantly correlated with CFR (r = -0.686, p < 0.01), DDT (r = -0.727, p < 0.01), and DDT adeno (r = -0.780, p < 0.01). CFR and DDT adeno in multivariate analysis remained independent IS predictors after adjustment for other covariates and offered incremental prognostic value in models based on conventional clinical, angiographic, electrocardiographic and enzymatic variables. In predicting large infarction (IS > 20 %), the best cut-off for CFR was <1.73 (sensitivity 65 %, specificity 96 %) and for DDT adeno ≤720 ms (sensitivity 81 %, specificity 96 %). CFR and DDT during adenosine are independent and powerful early predictors of final IS offering incremental prognostic information over conventional parameters of myocardial and microvascular damage and tissue reperfusion.

Published
2014
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47. The randomized physiologic assessment of thrombus aspiration in patients with acute ST-segment elevation myocardial infarction trial (PATA STEMI): study rationale and design.

Author

Orlic D, Ostojic M, Beleslin B, Milasinovic D, Tesic M, Borovic M, Vukcevic V, Stojkovic S, Nedeljkovic M, and Stankovic G

Subjects
Coronary Circulation, Coronary Thrombosis complications, Humans, Microcirculation, Myocardial Infarction etiology, Percutaneous Coronary Intervention, Prospective Studies, Vascular Resistance, Coronary Thrombosis therapy, Myocardial Infarction therapy, Thrombectomy
Abstract

Introduction: Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI., Study Design: PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months., Conclusion: If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI., (© 2014, Wiley Periodicals, Inc.)

Published
2014
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48. Coronary vasomotion one year after drug-eluting stent implantation: comparison of everolimus-eluting and paclitaxel-eluting coronary stents.

Author

Hamilos M, Ribichini F, Ostojic MC, Ferrero V, Orlic D, Vassanelli C, Karanovic N, Sarno G, Cuisset T, Vardas PE, and Wijns W

Subjects
Aged, Coronary Angiography, Coronary Artery Disease diagnosis, Coronary Artery Disease physiopathology, Coronary Vessels diagnostic imaging, Coronary Vessels physiopathology, Endothelium, Vascular diagnostic imaging, Endothelium, Vascular physiopathology, Europe, Everolimus, Female, Humans, Male, Middle Aged, Percutaneous Coronary Intervention adverse effects, Prospective Studies, Prosthesis Design, Sirolimus administration & dosage, Time Factors, Treatment Outcome, Cardiovascular Agents administration & dosage, Coronary Artery Disease therapy, Coronary Vessels drug effects, Drug-Eluting Stents, Endothelium, Vascular drug effects, Hemodynamics drug effects, Paclitaxel administration & dosage, Percutaneous Coronary Intervention instrumentation, Sirolimus analogs & derivatives
Abstract

First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5 ± 3.6 vs -4.2 ± 6.9, p < 0.001) and distal (+4.6 ± 7.9 vs -4.8 ± 9.3, p = 0.003) segments. The reference segment did not show any significant difference in vasodilatation between the two groups (+9.8 ± 6.4 vs +7.2 ± 5.2, p = 0.17). Endothelium-dependent vasomotion at adjacent stent segments is relatively preserved after EES implantation while vasoconstriction was observed after PES implantation.

Published
2014
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49. Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function.

Author

Trifunovic D, Stankovic S, Sobic-Saranovic D, Marinkovic J, Petrovic M, Orlic D, Beleslin B, Banovic M, Vujisic-Tesic B, Petrovic M, Nedeljkovic I, Stepanovic J, Djordjevic-Dikic A, Tesic M, Djukanovic N, Petrovic O, Vasovic O, Nestorovic E, Kostic J, Ristic A, and Ostojic M

Subjects
Acute Disease, Aged, Female, Humans, Male, Middle Aged, Myocardial Infarction diagnosis, Prospective Studies, Coronary Circulation physiology, Insulin Resistance physiology, Microcirculation physiology, Myocardial Infarction physiopathology, Myocardial Infarction surgery, Percutaneous Coronary Intervention methods
Abstract

Background: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI)., Methods: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices., Results: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026)., Conclusion: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

Published
2014
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50. Shear stress-induced mechanotransduction protein deregulation and vasculopathy in a mouse model of progeria.

Author

Song M, San H, Anderson SA, Cannon RO 3rd, and Orlic D

Subjects
Animals, Disease Models, Animal, Gene Expression, Humans, Intermediate Filament Proteins metabolism, Lamin Type A, Mechanotransduction, Cellular, Mice, Muscle, Smooth, Vascular metabolism, Muscle, Smooth, Vascular pathology, Nuclear Proteins metabolism, Protein Precursors metabolism, Stress, Mechanical, Progeria metabolism, Progeria pathology, Vascular Diseases metabolism, Vascular Diseases pathology
Abstract

Introduction: A mouse model of progeria derived by insertion of the human mutant LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in the media of the ascending aorta. We hypothesized that high shear stress, in the presence of mutant lamin A, induces this vasculopathy and tried to define the molecular and cellular basis for aortic vasculopathy., Methods: Ascending and descending aortas from wild type (WT) and mLMNA+ mice were compared using proteomics, Western blots, PCR and immunostaining. To determine whether high fluidic shear stress, known to occur in the ascending aorta, contributed to the vasculopathy, we exposed descending aortas of mLMNA+ mice, with no apparent vasculopathy, to 75 dynes/cm2 shear stress for 30 minutes using a microfluidic system., Results: When the mice were one year of age, expression of several mechanotransduction proteins in the ascending aorta, including vimentin, decreased in mLMNA+ mice but no decrease occurred in the descending aorta. High fluidic shear stress produced a significant reduction in vimentin of mLMNA+ mice but not in similarly treated WT mice., Conclusions: The occurrence of mutant lamin A and high shear stress correlate with a reduction in the level of mechanotransduction proteins in smooth muscle cells of the media. Reduction of these proteins may contribute over time to development of vasculopathy in the ascending aorta in progeria syndrome.

Published
2014
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