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Papers by Miran Sebestjen

Research paper thumbnail of Coronary Allograft Vasculopathy is Associated with Decreased CD34+ Cell Count in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2021

Purpose The underlying mechanisms of coronary allograft vasculopathy (CAV) after heart transplant... more Purpose The underlying mechanisms of coronary allograft vasculopathy (CAV) after heart transplantation remain incompletely understood. Since CD34+ cells represent one of the key determinants of coronary vascular homeostasis we investigated the potential association between CAV and CD34+ cell count in heart transplant recipients. Methods In a single-center prospective pilot study we included 18 adult heart transplant recipients without history of congenital heart disease, multi-organ transplantation or oncologic therapy. All patients underwent coronary CT angiography and CAV was defined in accordance with the ISHT criteria. At the time of CT angiography we collected blood samples and measured CD34+ cell count using Beckman-Coulter Navios EX flow cytometry according to ISAGE protocol. Results CAV was present in 6 patients (33%; Group A) and absent in 12 patients (67%; Group B). The two groups did not differ in age (58±8 years in Group A vs. 53±14 years in Group B,P=0.46), gender (male: 100% vs. 83% in Group B,P=0.31), underlying disease etiology (ischemic: 67% vs. 33%,P=0.20), presence of hypertension (83% vs. 75%,P=0.70), diabetes (50% vs. 33%,P=0.52) or renal insufficiency (17% vs. 33%,P=0.48). Furthermore, donor age (45±9 years in Group A vs. 38±10 years in Group B,P=0.22), allograft ischemic time (205±68 min vs. 193±63 min,P=0.72), tacrolimus trough levels (6.9±1.3 μg/L vs. 6.8±1.2 μg/L,P=0.76), and NT-proBNP levels (478±288 pg/mL vs. 473±373 pg/mL,P=0.97) were comparable. Though total leukocyte count was similar (7.5±3.4 × 109/L in Group A vs. 6.8±2.1 × 109/L in Group B,P=0.60), we found significantly lower CD34+ cell count in Group A compared to Group B (1.37±0.36 × 106/L vs. 2.15±0.81 × 106/L,P=0.04). When stratifying patients according to CD34+ cell count, patients with cell count below the median displayed increased incidence of CAV compared to patients with cell count above the median (55% vs. 11%,P=0.04). Overall, patients with CAV ISHLT score>1 had lower CD34+ count when compared patients with ISHLT grade 1 CAV (0.91±0.06 × 106/L vs. 1.32±0.14 × 106/L,P=0.03). Conclusion Lower CD34+ cell count appears to be associated with CAV in heart transplant recipients. Further clinical trials are warranted to better define the underlying mechanisms and investigate the potential of CD34+ cells in the prevention and treatment of CAV in this patient cohort.

Research paper thumbnail of Abstract 12258: Angiotensin Receptor-neprilysin Inhibitor Therapy is Associated With Improved Echocardiographic Parameters in Chronic Heart Failure Patients With Reduced Ejection Fraction

Circulation, Nov 19, 2019

Research paper thumbnail of Prognostic Significance of Early Leukopenia in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2022

Research paper thumbnail of Abstract 17213: CD34+ Cell Therapy is Associated With Decreased Hospital Readmission in Patients With Chronic Heart Failure

Circulation, Nov 14, 2017

Introduction: Hospital readmissions due to worsening heart failure have been associated with adve... more Introduction: Hospital readmissions due to worsening heart failure have been associated with adverse prognosis in chronic heart failure patients. Hypothesis: We sought to investigate the effects of...

Research paper thumbnail of Safety and Efficacy of Extended Release Tacrolimus After Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2018

Purpose: Elevated pre-transplant red cell distribution width (RDW) is an established marker of bo... more Purpose: Elevated pre-transplant red cell distribution width (RDW) is an established marker of bone marrow dysfunction and poor survival in heart failure population. We sought to investigate a correlation between post-transplant RDW and long-term outcome after heart transplantation (HTX). Methods: We retrospectively reviewed demographic, biochemical, transplant and 3-year outcome data of patients undergoing HTX at our center between 2010 and 2013. Patients with iron deficiency, anemia or patients on LVAD support prior HTX were excluded. All recipients underwent scheduled myocardial biopsies. Late rejection was defined when occurring ˃ 12 months post HTX. RDW was measured at 1, 3, 6, 9 and 12 months after HTX and was considered normal if< 14.5%. All recipients received standard immunoinduction (basiliximab) and maintenance (CNI/MMF/steroids) immunosupression therapy. Results: In all recipients RDW values decreased in first 9 months and reached steady-state by 12 months post HTX. At 12 months post HTX 48 (52%) recipients reached normal RDW (Group A) and 44 (48%) recipients had elevated RDW (Group B). The two groups did not differ in age (54±12 years in Group A vs. 53±12 years in Group B;P= 0.70), gender (male: 81% vs. 80%;P= 0.84), serum creatinine (103±34 µmol/L vs. 90±36 µmol/L;P= 0.12), hypertension (62% vs. 59%;P= 0.74), diabetes (25% vs. 34%;P= 0.34), donor age (43±13 years vs. 42±12 years;P= 0.94) or graft ischemic time (186±77 min vs. 179±64 min;P= 0.65). Both groups had similar left ventricular EF (66±9% in Group A vs. 62±8%;P= 0.20), mean tacrolimus C0 levels (7.3±2.7 ng/mL in Group A vs. 7.1±2.3 ng/mL in Group B;P= 0.33), dose of MMF (2318±472 mg vs. 2124±312 mg;P= 0.44) and metylprednisolone (4 mg qd in both groups) at 12 months post-HTX. However significantly less late rejection episodes were found in Group A than in Group B (16% vs. 39%;P= 0.01) with similar median time to late rejection episode (403 days in Group A and 478 days in Group B,P= 0.11). One patient in Group A and 2 patients in Group B had rejection˃1R. Conclusion: Elevated RDW at 12 months post-HTX appears to be associated with increased incidence of late allograft rejection. Although the underlying mechanisms remain to be defined, they may be related to diminished graft adaptation in the presence of persistently decreased bone marrow reserve, reflected by elevated RDW.

Research paper thumbnail of Preemptive Tuberculosis Prophylaxis vs. Watchful Waiting After Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2018

Methods: Single center, retrospective analysis of 113 HTx recipients at intermediate risk for CMV... more Methods: Single center, retrospective analysis of 113 HTx recipients at intermediate risk for CMV (R+) from 1/2011-4/2017 at Emory University. Patients were divided into preemptive prophylaxis vs. upfront prophylaxis. The primary endpoint studied was time to first NCHVI. Results: Of 113 intermediate risk patients, 76 (67%) underwent a preemptive approach, and 37 (33%) received upfront prophylaxis. Overall 16/76 (21%) patients in the preemptive group were treated for NCHVI compared to 2/37 (5%) in the upfront prophylaxis group (p = 0.033). Kaplan Meier analysis showed significantly worse freedom from NCHVI in the preemptive group (Figure 1, log rank p = 0.031). Univariate Cox Regression analysis showed a 4-fold higher risk of NCHVI with the preemptive strategy (p = 0.049). Multivariable analysis showed similar results with borderline statistical significance (p = 0.061) (Table 1). Conclusion: A preemptive prophylaxis strategy for CMV in intermediate risk patients is associated with higher risk for NCHVI.

Research paper thumbnail of Myocardial Scar Burden Correlates with NT-proBNP Levels and Changes in Left Ventricular Filling Pressures in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2021

Research paper thumbnail of Clinical Effects of CD34+ Cell Therapy in Advanced Chronic Heart Failure Patients Listed for Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2021

Research paper thumbnail of QuantiFERON-CMV guided virostatic prophylaxis after heart transplantation

Journal of Heart and Lung Transplantation, Mar 1, 2020

gather data. We started to use isavuconazole as Aspergillus prophylaxis in place of voriconazole ... more gather data. We started to use isavuconazole as Aspergillus prophylaxis in place of voriconazole in December 2016. Results: Sixteen patients in 2015 and 11 patients in 2016 underwent single or double lung transplantation. Nine patients were newly diagnosed with invasive aspergillosis in 2015. After switching to isavuconazole as Aspergillus prophylaxis in 2016, only 3 patients of the 11 that were transplanted were newly diagnosed with invasive aspergillosis. Conclusion: Our pilot study reveals that isavuconazole is an effective Aspergillus prophylaxis agent in lung transplant recipients. Isavuconazole has good bioavailability of the oral formulation, predictable pharmacokinetics in adults, few serious adverse effects, and less drug-drug interactions than those noted with voriconazole. Further investigation on use of isavuconazole as Aspergillus prophylaxis is warranted.

Research paper thumbnail of Abstract 15678: The Introduction of Novel Heart Failure Therapy in Patients With Non-Compaction Cardiomyopathy Leads to an Improvement of Heart Failure

Circulation

Introduction: In patients with noncompaction cardiomyopathy (NCC) no heart failure (HF) therapy h... more Introduction: In patients with noncompaction cardiomyopathy (NCC) no heart failure (HF) therapy has been shown to improve the left ventricle ejection fraction (LVEF). Sudden cardiac death (SCD) or need for heart transplantation (HTx) or left ventricle assist device (LVAD) implantation have been described. The effect of novel HF therapy, such as angiotensin receptor and neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2i) remains unclear. Hypothesis: We sought to analyze a potential recovery of cardiac function in patients with NCC after introducing the novel HF therapy. Methods: We have prospectively enrolled 41 (33 male, 8 female) patients with NCC, confirmed by cardiac MRI from 2018 to 2021. The average age was 49±16.3 years. At inclusion, echocardiography was performed to determine the left ventricle end-diastolic diameter and volume (EDD and EDV) and LVEF; serum levels of NT-proBNP have also been obtained. ARNI and SGLT2i have been introduced into ...

Research paper thumbnail of Short-Term Outcome after Heart Transplantation is Comparable When Using Extended-Criteria Donors

Journal of Heart and Lung Transplantation, Apr 1, 2019

Purpose: The lack of donor organs limits the availability of heart transplantation as an optimal ... more Purpose: The lack of donor organs limits the availability of heart transplantation as an optimal treatment option for advanced heart failure patients. In an effort to expand a pool of acceptable donor organs we explored a correlation between donor age and 1-year outcome in patients undergoing heart transplantation. Methods: A retrospective cohort study was performed of all heart transplant reciepients at our center between 2006 and 2013. We reviewed the demographic, biochemical, transplant, donor and 1-year outcome data. An age threshold for extended criteria organs was set at 50 years. All patients received standard immunoinduction (basiliximab and steroids) and maintenance (CNI/MMF/steroids) immunosupression therapy. Results: Of 133 patients 96 (72%) recieved non-extended criteria organ (Group A) and 34 (28%) recieved extended criteria organ (Group B). The two groups did not differ significantly regarding age (49.1 §11.3 years in Group A vs. 51.9 §6.4 years in Group B; P=0.1), male gender (72% vs. 82%;P=0.31), the presence of kidney dysfunction (31% vs. 18%; P=0.18), arterial hypertension (58% vs. 50%; P=0.44), diabetes (21% vs. 25%; P=0.69) and hyperlipidemia (40% vs. 50%; P=0.38). Also no differences were observed considering graft ischemic time (167 §69 min vs. 195 §64 min; P=0.07), donor norepinephrine vasoactive support (0,13 §0,14 mcg/ kg/min vs. 0,21 §0,29 mcg/kg/min;P=0,07) and the nubmer of donor risk factors for coronary artery disease (0,8 §0,9 vs. 1,0 §1,1;P=0,18). Also the incidence of coronary vasculopathy (4% vs. 7%; P=0.63) and allograft rejection within first posttransplant year (10% vs. 7%;P=0.58) was not different between the two groups. Pre-explantation echocardiography was available in 100% in both groups. However, coronary angiography was used significantly more fequently in extened criteria organs (59 §5% Group B vs. 11 §3% Group A;P<0,001). One year mortality did not differ between the two groups (16% in Group A vs. 14% in Group B; P=0,75). Conclusion: Detailed evaluation of extended criteria donor organs may aid expand a pool of organs, available for transplantation without compromising short-term outcome of heart transplant receipients.

Research paper thumbnail of Smoking and Diabetes Attenuate Number of CD34+ Haematopoietic Stem Cells in Peripheral Blood of Patients with Advanced Peripheral Artery Disease

International Journal of Molecular Sciences

Peripheral artery disease (PAD) is a globally prevalent problem with limited treatment options, l... more Peripheral artery disease (PAD) is a globally prevalent problem with limited treatment options, leaving up to a fifth of patients remediless. The emergence of new studies on cell therapy in recent years offers a new promising option for their treatment. Our aim was to explore how the number of CD34+ hematopoietic cells in the peripheral blood of PAD patients is associated with patients’ functional as well as atherogenic factors. We selected 30 patients with advanced PAD, recorded their performance in a walking test in standard conditions and sampled their blood for further analysis with an emphasis on CD34+ cell selection and counting. No correlation of the CD34+ cell number was confirmed with any of the observed laboratory parameters. There was an association between the claudication distance and the number of CD34+ cells (r = −0.403, p = 0.046). The number of CD34+ cells differed between patients with and without type II diabetes (p = 0.071) and between active smokers, past smoker...

Research paper thumbnail of Improvement of Endothelial Function with Spironolactone Treatment in Non-Obese Women with Polycystic Ovary Syndrome

Research paper thumbnail of The influence of atorvastatin on walking performance in peripheral arterial disease

VASA, May 1, 2009

Einfl uss von atorvastatin auf die Gehstrecke bei peripherer arterieller Verschlusskrankheit Hint... more Einfl uss von atorvastatin auf die Gehstrecke bei peripherer arterieller Verschlusskrankheit Hintergrund. Es ist kürzlich gezeigt worden, dass mit Statinen (in hohen Dosen) die freie Gehstrecke bei Patienten mit peripherer arterieller Verschlusskrankheit verlängert werden kann. Wir haben untersucht, ob Statine in einer moderaten Dosierung, die noch für eine wirksame Senkung der Hypercholesterinämie ausreichend ist, die freie Gehstrecke bei Patienten mit peripherer arterieller Verschlusskrankheit verbessern können. Patienten und Methoden: 37 Patienten mit Hypercholesterinämie (LDL Cholesterin = 3.46 ± 0.13 mmol/l), die nicht mit Statinen vorbehandelt waren, wurden in einer Doppelblindstudie in zwei Gruppen randomisiert: die eine erhielt 20 mg Atorvastatin täglich, die andere Placebo (N = 17). Alle Patienten hatten eine stabile Claudicatio intermittens (Fontaine Stadium IIa oder IIb). Als Grundlage wurde bei allen Patienten die schmerzfreie Gehdistanz nach einem und drei Monaten gemessen. Ergebnisse: Nach 3 Monaten hatten die Patienten in der mit Atorvastatin behandelten Gruppe die Zielwerte für Cholesterin erreicht (LDL Cholesterin = 2.34 ± 0.9 mmol/l), während in der Kontrollgruppe keine signifi kante Veränderung der Lipidwerte zu verzeichnen war. Der ankle-brachial pressure index (ABPI) blieb in beiden Gruppen unverändert. Nach 3 Monaten war die schmerzfreie Gehstrecke signifikant verlängert (p < 0.001), dies allerdings in beiden Gruppen (bei Studienbeginn: 56 (53-108) Meter vs. 53 (53-106) Meter; nach 3 Monaten: 79 (53-108) Meter vs. 106 (66-159) Meter, für die Atorvastatin Gruppe respektive die Placebo Gruppe. Dementsprechend muss dieser Effekt der geregelten physischen Aktivität zugeschrieben werden, nicht der Anwendung von Statinen. Schlussfolgerungen: Unsere Ergebnise zeigen, dass die routinemässige Behandlung mit Statinen (Atorvastatin 20 mg/ Tag) wohl eine wirksame Senkung des Cholesterins erzielt, nicht jedoch eine Verbesserung der freien Gehstrecke bei Patienten mit chonischer arterieller Verschlusskrankheit verursacht.

Research paper thumbnail of Abstract 14057: Both Trimetizidine and Ranolazine Improve Arterial Vasoreactivity in Patients With Ischemic Heart Disease

Introduction: Endothelium-dependent and independent vasodilator dysfunction are independent predi... more Introduction: Endothelium-dependent and independent vasodilator dysfunction are independent predictors of disease progression of atherosclerosis and rates of cardiovascular events in patients with ischemic heart disease. Ranolazine and trimetazidine are novel drugs that reduce angina symptoms in patients with ischemic heart disease. The aim of this study was to compare the effects of ranolazine and trimetazidine on endothelium dependent and independent arterial dilation. Design: In a prospective, double blind study, 52 males aged between 18 to 65 years with chronic ischemic heart disease were randomised and submitted to 12 weeks treatment with either trimetazidine (35 mg twice daily) or ranolazine. Ranolazine was given in a dose of 375 mg twice daily for 4 weeks and was increased to 500 mg twice daily. Flow-mediated (endothelium-dependent) dilation (FMD) and nitroglycerin-induced (endothelium-independent) (GTN) dilation of brachial artery were measured using high resolution ultrasound. Results: FMD increased from 3.5±7.4 to 13.8±9.4% (p Conclusions: Both trimetizedine and ranolazine lead to an improvement of endothelium-dependent and endothelium-independent dilation of brachial artery in the patients with ischemic heart disease. Due to greater increase of FMD/GTN ratio, we can assume that trimetazidine has more benefical effect on endothelium than ranolazine.

Research paper thumbnail of Haplotypes of two common polymorphisms in LPA gene are associated with Lp(a) concentration in coronary disease patients with extremely high Lp(a) levels

Atherosclerosis, Aug 1, 2021

Research paper thumbnail of Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors

Research Square (Research Square), Apr 26, 2023

Background In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-in amma... more Background In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-in ammatory, anti brinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. Methods Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of ow-mediated dilation of brachial artery (FMD), carotid intima-media

Research paper thumbnail of Atherosclerotic Cardiovascular Disease: Risk Assessment, Prevention and Treatment Strategies

Journal of Cardiovascular Development and Disease, Dec 14, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Ranolazine, But not Trimetazidine, Influences Markers of Inflammation in Patients with Stable Coronary Artery Disease

Biomedical Journal of Scientific and Technical Research, Mar 24, 2021

Inflammation has a critical role in the initiation and progression of the atherosclerotic process... more Inflammation has a critical role in the initiation and progression of the atherosclerotic process [1], with both pro-inflammatory and anti-inflammatory cytokines involved. The fate of atherosclerotic plaques and the clinical complications that can arise result from the balance between the pro-inflammatory and anti-inflammatory mediators that regulate the magnitude of the inflammatory response within plaques [2,3]. Among the inflammatory parameters, C-reactive protein (CRP) has been shown to be the most important factor in the prediction of future coronary artery events [4]. CRP is mainly synthesised in the liver, although extrahepatic transcription of CRP upon inflammatory stimuli with interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α has been described [5,6]. TNF-α is a multifunctional circulating cytokine that is the principal mediator of the acute inflammatory response.

Research paper thumbnail of Both, simvastatin and pravastatin improve flow-mediated dilation in males with hypercholesterolemia

Atherosclerosis Supplements, May 1, 2001

Research paper thumbnail of Coronary Allograft Vasculopathy is Associated with Decreased CD34+ Cell Count in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2021

Purpose The underlying mechanisms of coronary allograft vasculopathy (CAV) after heart transplant... more Purpose The underlying mechanisms of coronary allograft vasculopathy (CAV) after heart transplantation remain incompletely understood. Since CD34+ cells represent one of the key determinants of coronary vascular homeostasis we investigated the potential association between CAV and CD34+ cell count in heart transplant recipients. Methods In a single-center prospective pilot study we included 18 adult heart transplant recipients without history of congenital heart disease, multi-organ transplantation or oncologic therapy. All patients underwent coronary CT angiography and CAV was defined in accordance with the ISHT criteria. At the time of CT angiography we collected blood samples and measured CD34+ cell count using Beckman-Coulter Navios EX flow cytometry according to ISAGE protocol. Results CAV was present in 6 patients (33%; Group A) and absent in 12 patients (67%; Group B). The two groups did not differ in age (58±8 years in Group A vs. 53±14 years in Group B,P=0.46), gender (male: 100% vs. 83% in Group B,P=0.31), underlying disease etiology (ischemic: 67% vs. 33%,P=0.20), presence of hypertension (83% vs. 75%,P=0.70), diabetes (50% vs. 33%,P=0.52) or renal insufficiency (17% vs. 33%,P=0.48). Furthermore, donor age (45±9 years in Group A vs. 38±10 years in Group B,P=0.22), allograft ischemic time (205±68 min vs. 193±63 min,P=0.72), tacrolimus trough levels (6.9±1.3 μg/L vs. 6.8±1.2 μg/L,P=0.76), and NT-proBNP levels (478±288 pg/mL vs. 473±373 pg/mL,P=0.97) were comparable. Though total leukocyte count was similar (7.5±3.4 × 109/L in Group A vs. 6.8±2.1 × 109/L in Group B,P=0.60), we found significantly lower CD34+ cell count in Group A compared to Group B (1.37±0.36 × 106/L vs. 2.15±0.81 × 106/L,P=0.04). When stratifying patients according to CD34+ cell count, patients with cell count below the median displayed increased incidence of CAV compared to patients with cell count above the median (55% vs. 11%,P=0.04). Overall, patients with CAV ISHLT score>1 had lower CD34+ count when compared patients with ISHLT grade 1 CAV (0.91±0.06 × 106/L vs. 1.32±0.14 × 106/L,P=0.03). Conclusion Lower CD34+ cell count appears to be associated with CAV in heart transplant recipients. Further clinical trials are warranted to better define the underlying mechanisms and investigate the potential of CD34+ cells in the prevention and treatment of CAV in this patient cohort.

Research paper thumbnail of Abstract 12258: Angiotensin Receptor-neprilysin Inhibitor Therapy is Associated With Improved Echocardiographic Parameters in Chronic Heart Failure Patients With Reduced Ejection Fraction

Circulation, Nov 19, 2019

Research paper thumbnail of Prognostic Significance of Early Leukopenia in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2022

Research paper thumbnail of Abstract 17213: CD34+ Cell Therapy is Associated With Decreased Hospital Readmission in Patients With Chronic Heart Failure

Circulation, Nov 14, 2017

Introduction: Hospital readmissions due to worsening heart failure have been associated with adve... more Introduction: Hospital readmissions due to worsening heart failure have been associated with adverse prognosis in chronic heart failure patients. Hypothesis: We sought to investigate the effects of...

Research paper thumbnail of Safety and Efficacy of Extended Release Tacrolimus After Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2018

Purpose: Elevated pre-transplant red cell distribution width (RDW) is an established marker of bo... more Purpose: Elevated pre-transplant red cell distribution width (RDW) is an established marker of bone marrow dysfunction and poor survival in heart failure population. We sought to investigate a correlation between post-transplant RDW and long-term outcome after heart transplantation (HTX). Methods: We retrospectively reviewed demographic, biochemical, transplant and 3-year outcome data of patients undergoing HTX at our center between 2010 and 2013. Patients with iron deficiency, anemia or patients on LVAD support prior HTX were excluded. All recipients underwent scheduled myocardial biopsies. Late rejection was defined when occurring ˃ 12 months post HTX. RDW was measured at 1, 3, 6, 9 and 12 months after HTX and was considered normal if< 14.5%. All recipients received standard immunoinduction (basiliximab) and maintenance (CNI/MMF/steroids) immunosupression therapy. Results: In all recipients RDW values decreased in first 9 months and reached steady-state by 12 months post HTX. At 12 months post HTX 48 (52%) recipients reached normal RDW (Group A) and 44 (48%) recipients had elevated RDW (Group B). The two groups did not differ in age (54±12 years in Group A vs. 53±12 years in Group B;P= 0.70), gender (male: 81% vs. 80%;P= 0.84), serum creatinine (103±34 µmol/L vs. 90±36 µmol/L;P= 0.12), hypertension (62% vs. 59%;P= 0.74), diabetes (25% vs. 34%;P= 0.34), donor age (43±13 years vs. 42±12 years;P= 0.94) or graft ischemic time (186±77 min vs. 179±64 min;P= 0.65). Both groups had similar left ventricular EF (66±9% in Group A vs. 62±8%;P= 0.20), mean tacrolimus C0 levels (7.3±2.7 ng/mL in Group A vs. 7.1±2.3 ng/mL in Group B;P= 0.33), dose of MMF (2318±472 mg vs. 2124±312 mg;P= 0.44) and metylprednisolone (4 mg qd in both groups) at 12 months post-HTX. However significantly less late rejection episodes were found in Group A than in Group B (16% vs. 39%;P= 0.01) with similar median time to late rejection episode (403 days in Group A and 478 days in Group B,P= 0.11). One patient in Group A and 2 patients in Group B had rejection˃1R. Conclusion: Elevated RDW at 12 months post-HTX appears to be associated with increased incidence of late allograft rejection. Although the underlying mechanisms remain to be defined, they may be related to diminished graft adaptation in the presence of persistently decreased bone marrow reserve, reflected by elevated RDW.

Research paper thumbnail of Preemptive Tuberculosis Prophylaxis vs. Watchful Waiting After Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2018

Methods: Single center, retrospective analysis of 113 HTx recipients at intermediate risk for CMV... more Methods: Single center, retrospective analysis of 113 HTx recipients at intermediate risk for CMV (R+) from 1/2011-4/2017 at Emory University. Patients were divided into preemptive prophylaxis vs. upfront prophylaxis. The primary endpoint studied was time to first NCHVI. Results: Of 113 intermediate risk patients, 76 (67%) underwent a preemptive approach, and 37 (33%) received upfront prophylaxis. Overall 16/76 (21%) patients in the preemptive group were treated for NCHVI compared to 2/37 (5%) in the upfront prophylaxis group (p = 0.033). Kaplan Meier analysis showed significantly worse freedom from NCHVI in the preemptive group (Figure 1, log rank p = 0.031). Univariate Cox Regression analysis showed a 4-fold higher risk of NCHVI with the preemptive strategy (p = 0.049). Multivariable analysis showed similar results with borderline statistical significance (p = 0.061) (Table 1). Conclusion: A preemptive prophylaxis strategy for CMV in intermediate risk patients is associated with higher risk for NCHVI.

Research paper thumbnail of Myocardial Scar Burden Correlates with NT-proBNP Levels and Changes in Left Ventricular Filling Pressures in Heart Transplant Recipients

Journal of Heart and Lung Transplantation, Apr 1, 2021

Research paper thumbnail of Clinical Effects of CD34+ Cell Therapy in Advanced Chronic Heart Failure Patients Listed for Heart Transplantation

Journal of Heart and Lung Transplantation, Apr 1, 2021

Research paper thumbnail of QuantiFERON-CMV guided virostatic prophylaxis after heart transplantation

Journal of Heart and Lung Transplantation, Mar 1, 2020

gather data. We started to use isavuconazole as Aspergillus prophylaxis in place of voriconazole ... more gather data. We started to use isavuconazole as Aspergillus prophylaxis in place of voriconazole in December 2016. Results: Sixteen patients in 2015 and 11 patients in 2016 underwent single or double lung transplantation. Nine patients were newly diagnosed with invasive aspergillosis in 2015. After switching to isavuconazole as Aspergillus prophylaxis in 2016, only 3 patients of the 11 that were transplanted were newly diagnosed with invasive aspergillosis. Conclusion: Our pilot study reveals that isavuconazole is an effective Aspergillus prophylaxis agent in lung transplant recipients. Isavuconazole has good bioavailability of the oral formulation, predictable pharmacokinetics in adults, few serious adverse effects, and less drug-drug interactions than those noted with voriconazole. Further investigation on use of isavuconazole as Aspergillus prophylaxis is warranted.

Research paper thumbnail of Abstract 15678: The Introduction of Novel Heart Failure Therapy in Patients With Non-Compaction Cardiomyopathy Leads to an Improvement of Heart Failure

Circulation

Introduction: In patients with noncompaction cardiomyopathy (NCC) no heart failure (HF) therapy h... more Introduction: In patients with noncompaction cardiomyopathy (NCC) no heart failure (HF) therapy has been shown to improve the left ventricle ejection fraction (LVEF). Sudden cardiac death (SCD) or need for heart transplantation (HTx) or left ventricle assist device (LVAD) implantation have been described. The effect of novel HF therapy, such as angiotensin receptor and neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2i) remains unclear. Hypothesis: We sought to analyze a potential recovery of cardiac function in patients with NCC after introducing the novel HF therapy. Methods: We have prospectively enrolled 41 (33 male, 8 female) patients with NCC, confirmed by cardiac MRI from 2018 to 2021. The average age was 49±16.3 years. At inclusion, echocardiography was performed to determine the left ventricle end-diastolic diameter and volume (EDD and EDV) and LVEF; serum levels of NT-proBNP have also been obtained. ARNI and SGLT2i have been introduced into ...

Research paper thumbnail of Short-Term Outcome after Heart Transplantation is Comparable When Using Extended-Criteria Donors

Journal of Heart and Lung Transplantation, Apr 1, 2019

Purpose: The lack of donor organs limits the availability of heart transplantation as an optimal ... more Purpose: The lack of donor organs limits the availability of heart transplantation as an optimal treatment option for advanced heart failure patients. In an effort to expand a pool of acceptable donor organs we explored a correlation between donor age and 1-year outcome in patients undergoing heart transplantation. Methods: A retrospective cohort study was performed of all heart transplant reciepients at our center between 2006 and 2013. We reviewed the demographic, biochemical, transplant, donor and 1-year outcome data. An age threshold for extended criteria organs was set at 50 years. All patients received standard immunoinduction (basiliximab and steroids) and maintenance (CNI/MMF/steroids) immunosupression therapy. Results: Of 133 patients 96 (72%) recieved non-extended criteria organ (Group A) and 34 (28%) recieved extended criteria organ (Group B). The two groups did not differ significantly regarding age (49.1 §11.3 years in Group A vs. 51.9 §6.4 years in Group B; P=0.1), male gender (72% vs. 82%;P=0.31), the presence of kidney dysfunction (31% vs. 18%; P=0.18), arterial hypertension (58% vs. 50%; P=0.44), diabetes (21% vs. 25%; P=0.69) and hyperlipidemia (40% vs. 50%; P=0.38). Also no differences were observed considering graft ischemic time (167 §69 min vs. 195 §64 min; P=0.07), donor norepinephrine vasoactive support (0,13 §0,14 mcg/ kg/min vs. 0,21 §0,29 mcg/kg/min;P=0,07) and the nubmer of donor risk factors for coronary artery disease (0,8 §0,9 vs. 1,0 §1,1;P=0,18). Also the incidence of coronary vasculopathy (4% vs. 7%; P=0.63) and allograft rejection within first posttransplant year (10% vs. 7%;P=0.58) was not different between the two groups. Pre-explantation echocardiography was available in 100% in both groups. However, coronary angiography was used significantly more fequently in extened criteria organs (59 §5% Group B vs. 11 §3% Group A;P<0,001). One year mortality did not differ between the two groups (16% in Group A vs. 14% in Group B; P=0,75). Conclusion: Detailed evaluation of extended criteria donor organs may aid expand a pool of organs, available for transplantation without compromising short-term outcome of heart transplant receipients.

Research paper thumbnail of Smoking and Diabetes Attenuate Number of CD34+ Haematopoietic Stem Cells in Peripheral Blood of Patients with Advanced Peripheral Artery Disease

International Journal of Molecular Sciences

Peripheral artery disease (PAD) is a globally prevalent problem with limited treatment options, l... more Peripheral artery disease (PAD) is a globally prevalent problem with limited treatment options, leaving up to a fifth of patients remediless. The emergence of new studies on cell therapy in recent years offers a new promising option for their treatment. Our aim was to explore how the number of CD34+ hematopoietic cells in the peripheral blood of PAD patients is associated with patients’ functional as well as atherogenic factors. We selected 30 patients with advanced PAD, recorded their performance in a walking test in standard conditions and sampled their blood for further analysis with an emphasis on CD34+ cell selection and counting. No correlation of the CD34+ cell number was confirmed with any of the observed laboratory parameters. There was an association between the claudication distance and the number of CD34+ cells (r = −0.403, p = 0.046). The number of CD34+ cells differed between patients with and without type II diabetes (p = 0.071) and between active smokers, past smoker...

Research paper thumbnail of Improvement of Endothelial Function with Spironolactone Treatment in Non-Obese Women with Polycystic Ovary Syndrome

Research paper thumbnail of The influence of atorvastatin on walking performance in peripheral arterial disease

VASA, May 1, 2009

Einfl uss von atorvastatin auf die Gehstrecke bei peripherer arterieller Verschlusskrankheit Hint... more Einfl uss von atorvastatin auf die Gehstrecke bei peripherer arterieller Verschlusskrankheit Hintergrund. Es ist kürzlich gezeigt worden, dass mit Statinen (in hohen Dosen) die freie Gehstrecke bei Patienten mit peripherer arterieller Verschlusskrankheit verlängert werden kann. Wir haben untersucht, ob Statine in einer moderaten Dosierung, die noch für eine wirksame Senkung der Hypercholesterinämie ausreichend ist, die freie Gehstrecke bei Patienten mit peripherer arterieller Verschlusskrankheit verbessern können. Patienten und Methoden: 37 Patienten mit Hypercholesterinämie (LDL Cholesterin = 3.46 ± 0.13 mmol/l), die nicht mit Statinen vorbehandelt waren, wurden in einer Doppelblindstudie in zwei Gruppen randomisiert: die eine erhielt 20 mg Atorvastatin täglich, die andere Placebo (N = 17). Alle Patienten hatten eine stabile Claudicatio intermittens (Fontaine Stadium IIa oder IIb). Als Grundlage wurde bei allen Patienten die schmerzfreie Gehdistanz nach einem und drei Monaten gemessen. Ergebnisse: Nach 3 Monaten hatten die Patienten in der mit Atorvastatin behandelten Gruppe die Zielwerte für Cholesterin erreicht (LDL Cholesterin = 2.34 ± 0.9 mmol/l), während in der Kontrollgruppe keine signifi kante Veränderung der Lipidwerte zu verzeichnen war. Der ankle-brachial pressure index (ABPI) blieb in beiden Gruppen unverändert. Nach 3 Monaten war die schmerzfreie Gehstrecke signifikant verlängert (p < 0.001), dies allerdings in beiden Gruppen (bei Studienbeginn: 56 (53-108) Meter vs. 53 (53-106) Meter; nach 3 Monaten: 79 (53-108) Meter vs. 106 (66-159) Meter, für die Atorvastatin Gruppe respektive die Placebo Gruppe. Dementsprechend muss dieser Effekt der geregelten physischen Aktivität zugeschrieben werden, nicht der Anwendung von Statinen. Schlussfolgerungen: Unsere Ergebnise zeigen, dass die routinemässige Behandlung mit Statinen (Atorvastatin 20 mg/ Tag) wohl eine wirksame Senkung des Cholesterins erzielt, nicht jedoch eine Verbesserung der freien Gehstrecke bei Patienten mit chonischer arterieller Verschlusskrankheit verursacht.

Research paper thumbnail of Abstract 14057: Both Trimetizidine and Ranolazine Improve Arterial Vasoreactivity in Patients With Ischemic Heart Disease

Introduction: Endothelium-dependent and independent vasodilator dysfunction are independent predi... more Introduction: Endothelium-dependent and independent vasodilator dysfunction are independent predictors of disease progression of atherosclerosis and rates of cardiovascular events in patients with ischemic heart disease. Ranolazine and trimetazidine are novel drugs that reduce angina symptoms in patients with ischemic heart disease. The aim of this study was to compare the effects of ranolazine and trimetazidine on endothelium dependent and independent arterial dilation. Design: In a prospective, double blind study, 52 males aged between 18 to 65 years with chronic ischemic heart disease were randomised and submitted to 12 weeks treatment with either trimetazidine (35 mg twice daily) or ranolazine. Ranolazine was given in a dose of 375 mg twice daily for 4 weeks and was increased to 500 mg twice daily. Flow-mediated (endothelium-dependent) dilation (FMD) and nitroglycerin-induced (endothelium-independent) (GTN) dilation of brachial artery were measured using high resolution ultrasound. Results: FMD increased from 3.5±7.4 to 13.8±9.4% (p Conclusions: Both trimetizedine and ranolazine lead to an improvement of endothelium-dependent and endothelium-independent dilation of brachial artery in the patients with ischemic heart disease. Due to greater increase of FMD/GTN ratio, we can assume that trimetazidine has more benefical effect on endothelium than ranolazine.

Research paper thumbnail of Haplotypes of two common polymorphisms in LPA gene are associated with Lp(a) concentration in coronary disease patients with extremely high Lp(a) levels

Atherosclerosis, Aug 1, 2021

Research paper thumbnail of Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors

Research Square (Research Square), Apr 26, 2023

Background In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-in amma... more Background In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-in ammatory, anti brinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. Methods Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of ow-mediated dilation of brachial artery (FMD), carotid intima-media

Research paper thumbnail of Atherosclerotic Cardiovascular Disease: Risk Assessment, Prevention and Treatment Strategies

Journal of Cardiovascular Development and Disease, Dec 14, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Ranolazine, But not Trimetazidine, Influences Markers of Inflammation in Patients with Stable Coronary Artery Disease

Biomedical Journal of Scientific and Technical Research, Mar 24, 2021

Inflammation has a critical role in the initiation and progression of the atherosclerotic process... more Inflammation has a critical role in the initiation and progression of the atherosclerotic process [1], with both pro-inflammatory and anti-inflammatory cytokines involved. The fate of atherosclerotic plaques and the clinical complications that can arise result from the balance between the pro-inflammatory and anti-inflammatory mediators that regulate the magnitude of the inflammatory response within plaques [2,3]. Among the inflammatory parameters, C-reactive protein (CRP) has been shown to be the most important factor in the prediction of future coronary artery events [4]. CRP is mainly synthesised in the liver, although extrahepatic transcription of CRP upon inflammatory stimuli with interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α has been described [5,6]. TNF-α is a multifunctional circulating cytokine that is the principal mediator of the acute inflammatory response.

Research paper thumbnail of Both, simvastatin and pravastatin improve flow-mediated dilation in males with hypercholesterolemia

Atherosclerosis Supplements, May 1, 2001