Browsing by Author "Hazirolan, Tuncay"

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    Approach To Optimal Assessment Of Right Ventricular Remodelling In Heart Transplant Recipients: Insights From Myocardial Work Index, T1 Mapping, And Endomyocardial Biopsy
    (2023) Colak, Ayse; Duzgun, Selin Ardali; Hazirolan, Tuncay; Sezgin, Atilla; Donal, Erwan; Butcher, Steele C.; Ozdemir, Handan; Pirat, Bahar; Eroglu, Serpil; Muderrisoglu, Haldun; Sade, Leyla Elif; https://orcid.org/0000-0002-7528-3557; https://orcid.org/0000-0003-3737-8595; 35666833; X-8540-2019; AAQ-7583-2021
    Aims Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients. Methods and results Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 +/- 8.7%) and MWI (403.2 +/- 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage. Conclusion Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage.
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    Biochemical, Radiologic, Ultrastructural, and Genetic Evaluation of Iron Overload in Acute Leukemia and Iron-chelation Therapy
    (2014) Olcay, Lale; Hazirolan, Tuncay; Yildirmak, Yildiz; Erdemli, Esra; Terzi, Yunus Kasim; Arda, Kemal; Ozturkmen, Seda; Akyay, Arzu; Kaymak-Cihan, Meric; Bicakci, Zafer; Bal, Ceylan; https://orcid.org/0000-0001-5612-9696; https://orcid.org/0000-0002-4480-7784; 23887025; B-4372-2018; ABI-7551-2020
    Iron overload in hereditary hemochromatosis and hematologic malignancy has unfavorable effects on morbidity. Herein, 53 children (age 108.4 +/- 58.3 mo, 25 girls and 28 boys) with acute myeloblastic and lymphoblastic leukemia, who received 4 different chemotherapy protocols, were evaluated for iron overload throughout chemotherapy. Iron overload arose: (1) before chemotherapy, which was dependent on neither chemotherapy nor packed red blood cell transfusions and (2) after chemotherapy, which was dependent on the duration and nature of chemotherapy and partially on transfusion of packed red blood cells. Iron overload was documented in 75% of patients with a ferritin level >1000 ng/mL, by liver and heart magnetic resonance imaging, and they were administered iron-chelation therapy with success. Three of 10 radiologically iron-overloaded patients were heterozygous for H63D mutation. Aminolevulinic acid and porphobilinogen levels were normal. Light microscopic examination of the bone marrow revealed increased iron granules in erythroblasts, platelets, and megakaryocytes, iron-laden macrophages, free iron in the matrix, dyshematopoiesis, and apoptotic cells. Electron microscopic examination revealed iron-laden secondary lysosomes and autolysosomes in normoblasts and iron-laden primary granules in promyelocytes, irrelevant to the ferritin level, implying autophagia due to chemotherapy as a source of the excess iron. We think that iron overload, which is an important complication of acute leukemia, should be evaluated separately from transfusion overload, and the management principles specific to leukemia should be implemented.
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    The Impact of Iron Overload in Acute Leukemia: Chronic Inflammation, But Not the Presence of Nontransferrin Bound Iron is a Determinant of Oxidative Stress
    (2017) Olcay, Lale; Serteser, Mustafa; Kolay, Murat; Balci, Havva F.; Yildirim, Ulku M.; Tekgunduz, Sibel A.; Hazirolan, Tuncay; Terzi, Yunus K.; https://orcid.org/0000-0002-5684-0581; https://orcid.org/0000-0001-5612-9696; 28731917; AAK-3548-2021; B-4372-2018
    In the literature, studies on the oxidant effects of nontransferrin bound iron [NTBI (eLPI assay)] during chemotherapy of acute lymphoblastic leukemia and acute myeloblastic leukemia are lacking. We established NTBI and oxidative stress determinants (OSD), iron parameters, high-sensitive C-reactive protein (hs-CRP) levels, liver tests, cumulative chemotherapeutic doses, and transfused blood in 36 children with acute leukemia throughout chemotherapy. These parameters were determined at the beginning and end of chemotherapy blocks (11 time points) and in 20 healthy children using enzyme-linked immunosorbent assay, and colorimetric and fluorometric enzymatic methods. In acute lymphoblastic leukemia, NTBI, OSD, and hs-CRP were higher than controls at 4/11, 7/11, and 9/11 time points (P<0.05). At 3 time points, NTBI and OSD concurrently increased. Ferritin, soluble transferrin receptor, serum iron, and transferrin saturation were higher than in controls at 5 to 11/11 time points (P<0.05). Those with NTBI had higher iron parameters than those without NTBI (P<0.05), but showed similar OSD, hs-CRP, liver enzymes, cumulative chemotherapeutics, and transfused blood (P>0.05). OSD did not correlate with NTBI, but correlated with hs-CRP. In conclusion, NTBI is a poor predictor of OSD in acute leukemia possibly because of the heterogeneity of NTBI and chronic inflammation. Further studies are needed to delineate the pathophysiology of these diseases.
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    Multiparametric Assessment of Right Ventricular Function in Heart Transplant Recipients by Echocardiography and Relations with Pulmonary Hemodynamics
    (2023) Colak, Ayse; Erdemir, Ahmet Gurkan; Hazirolan, Tuncay; Pirat, Bahar; Eroglu, Serpil; Aydinalp, Alp; Muderrisoglu, Haldun; Sade, Leyla Elif; 0000-0002-1958-6158; 0000-0002-3761-8782; 37955614
    Objective: Right ventricular (RV) dilatation and dysfunction are usually present in heart transplant (HTx) patients and worsened with residual pulmonary hypertension (PH). We aimed to determine the ability of different echocardiographic modalities to evaluate RV function in comparison with cardiac magnetic resonance (CMR) and their relations with pulmonary hemodynamics in HTx patients.Methods: A total of 62 data sets [echocardiographic, hemodynamic, and CMR] were acquired from 35 HTx patients. Comprehensive echocardiography, including two-dimensional (2D) transthoracic echocardiography, speckle tracking echocardiography, and three-dimensional (3D) echocardiography, was performed. Mean pulmonary artery pressure (mPAP) was obtained invasively from right heart catheterization. The correlations between all echocardiographic parameters and CMR imaging data and the differences between patients with and without residual PH were evaluated.Results: Diastolic and systolic RV volumes and RV ejection fraction (RVEF) by 3D echocardiography correlated strongly with CMR-derived volumes and RVEF (r = .91, r = .79, r = .64; p < .0001 for each, respectively). Among other parameters, RV fractional area change (r = .439; p < .001) and RV free wall longitudinal strain (RVFW-LS) (r = -.34; p < .05) correlated moderately with CMR-RVEF, whereas tricuspid annulus S' velocity (r = .29; p < .05) and tricuspid annular systolic plane excursion (r = .27; p < .05) correlated weakly with CMR-RVEF. Additionally, 3D-RVEF and RVFW-LS were significantly decreased in studies with mPAP >= 20 mm Hg in comparison to those with mPAP < 20 mm Hg (47.7 +/- 3.7 vs. 50.9 +/- 5.3, p = .04 and -15.5 +/- 3.1 vs. -17.5 +/- 3, p = .03, respectively).Conclusion: The best method for the evaluation of RV function in HTx recipients is 3D echocardiography. Besides, the subclinical impact of residual PH on RV function can be best determined by RVFW-LS and 3D-RVEF in these patients.
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    T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients
    (2019) Sade, Leyla Elif; Hazirolan, Tuncay; Kozan, Hatice; Ozdemir, Handan; Hayran, Mutlu; Eroglu, Serpil; Pirat, Bahar; Sezgin, Atilla; Muderrisoglu, Haldun; 29680337; X-8540-2019
    OBJECTIVES The aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients. BACKGROUND Noninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection. METHODS Surveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h. RESULTS Median time to first rejection (16 grade 1 rejection, 15 grade >= 2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and >= 2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time >= 1,090 ms, extracellutar volume GLS >= 32%, GLS >-14%, and global circumferential strain >=-24% had 100% sensitivity and 100% negative predictive value to define grade >= 2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS > 16% and T1 time >= 1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly. CONCLUSIONS T1 mapping and echocardiographic GLS can serve to guide endomyocardial biopsy selectively. (C) 2019 by the American College of Cardiology Foundation.