|
1
|
Schuster L, Zaradzki M, Janssen H, Gallenstein N, Etheredge M, Hofmann I, Weigand MA, Immenschuh S, Larmann J. Heme oxygenase-1 modulates CD62E-dependent endothelial cell-monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice. Front Immunol 2025; 16:1447319. [PMID: 40124367 PMCID: PMC11925954 DOI: 10.3389/fimmu.2025.1447319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 02/11/2025] [Indexed: 03/25/2025] Open
Abstract
The main risk factor for developing transplant vasculopathy (TV) after solid organ transplantation is de-novo production of donor-specific antibodies (DSAs) binding to endothelial cells (ECs) within the graft's vasculature. Diverse leukocyte populations recruited into the vessel wall via activated ECs contribute to vascular inflammation. Subsequent smooth muscle cell proliferation results in intima hyperplasia, the pathophysiological correlate of TV. We demonstrated that incubating aortic EC with anti-HLA-I antibodies led to increased monocyte adhesion to and transmigration across an EC monolayer. Both occurred in a CD62E-dependent fashion and were sensitive toward the anti-inflammatory enzyme heme oxygenase (HO)-1 modulation. Using a murine heterotopic aortic transplantation model, we demonstrated that anti-MHC I antibody-induced TV is ameliorated by pharmacologically induced HO-1 and the application of anti-CD62E antibodies results in a deceleration of developing TV. HO-1 modulation is a promising therapeutic approach to prevent leukocyte recruitment and subsequent intima hyperplasia in TV and thus precludes organ failure.
Collapse
Affiliation(s)
- Laura Schuster
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
- Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
| | - Marcin Zaradzki
- Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Henrike Janssen
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Nadia Gallenstein
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Melanie Etheredge
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of Anesthesiology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany
| | - Ilse Hofmann
- Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Markus A. Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Stephan Immenschuh
- Department of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Jan Larmann
- Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany
- Department of Anesthesiology, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany
| |
Collapse
|
|
2
|
Quinn S, Catania R, Appadurai V, Wilcox JE, Weinberg RL, Lee DC, Carr JC, Markl M, Allen BD, Avery R. Cardiac MRI in Heart Transplantation: Approaches and Clinical Insights. Radiographics 2025; 45:e240142. [PMID: 39883577 DOI: 10.1148/rg.240142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2025]
Abstract
Orthotopic heart transplant (OHT) is a well-established therapy for end-stage heart failure that leads to improved long-term survival rates, with careful allograft surveillance essential for optimizing clinical outcomes after OHT. Unfortunately, complications can arise after OHT that can compromise the success of the OHT. Cardiac MRI is continually evolving, with a range of advanced techniques that can be applied to evaluate allograft structure and function. Understanding the unique features of cardiac MRI in OHT recipients, identifying findings suggestive of acute or chronic complications, and recognizing the limitations of this imaging modality are essential for accurate interpretation of cardiac MRI findings and subsequent clinical reporting. The authors address the anticipated postsurgical anatomy and functionality of the OHT. Emphasis is placed on the advanced functional and tissue characterization features that can be seen in the stable OHT recipient, including global longitudinal strain, late gadolinium enhancement, native T1 and T2 mapping, and extracellular volume fraction. Subsequently, the evidence for detection of acute cardiac allograft rejection with cardiac MRI comprehensive tissue characterization techniques and the role of quantitative myocardial perfusion for cardiac allograft vasculopathy screening are discussed, with reference to their comparative standard of reference screening tests, including endomyocardial biopsy, invasive coronary angiography, and myocardial rest and stress perfusion PET/CT. Cardiac MRI has been included in contemporary OHT management guidelines and therefore can be considered a complementary tool for allograft evaluation. The authors demonstrate the complementary role cardiac MRI can play in cardiac allograft surveillance, with clinical examples. ©RSNA, 2025 Supplemental material is available for this article. See the invited commentary by Agarwal in this issue.
Collapse
Affiliation(s)
- Sandra Quinn
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Roberta Catania
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Vinesh Appadurai
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Jane E Wilcox
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Richard L Weinberg
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Daniel C Lee
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - James C Carr
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Michael Markl
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Bradley D Allen
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| | - Ryan Avery
- From the Department of Radiology (S.Q., R.C., J.C.C., M.M., B.D.A., R.A.) and the Division of Cardiology, Department of Medicine (V.A., J.E.W., R.L.W., D.C.L.), Northwestern University Feinberg School of Medicine, 737 N Michigan Ave, Ste 1600, Chicago, IL 60611; Prince Charles Hospital, Chermside, Queensland, Australia (V.A.); and the Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, Ill (M.M.)
| |
Collapse
|
|
3
|
Belmonte M, Paolisso P, Viscusi MM, Beles M, Bergamaschi L, Sansonetti A, Ohashi H, Seki R, Gallinoro E, Esposito G, Shumkova M, Leone A, Masetti M, Barbato E, Verstreken S, Dierckx R, Heggermont W, Van Keer J, Potena L, Pizzi C, Bartunek J, Vanderheyden M. Comprehensive Non-invasive Versus Invasive Approach to Evaluate Cardiac Allograft Vasculopathy in Heart Transplantation: The CCTA-HTx Study. Circ Cardiovasc Imaging 2025; 18:e017197. [PMID: 39764680 DOI: 10.1161/circimaging.124.017197] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 10/28/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND Coronary computed tomography angiography (CCTA) is emerging as a valuable tool for noninvasive surveillance of cardiac allograft vasculopathy (CAV) in patients with heart transplant (HTx). We assessed the diagnostic performance of a comprehensive CCTA-based approach compared with the invasive reference, which includes invasive coronary angiography, intravascular ultrasound, and fractional flow reserve, for detecting CAV. METHODS This was a multicenter prospective study including 37 patients with HTx who underwent CCTA, invasive coronary angiography, intravascular ultrasound, and fractional flow reserve. The comprehensive CCTA-based approach included quantitative and qualitative plaque analysis and functional assessment by fractional flow reserve derived from coronary computed tomography. CAV was diagnosed based on invasive coronary angiography (International Society for Heart and Lung Transplantation criteria) and intravascular ultrasound. Univariable logistic regression analysis was performed to test CCTA-derived predictors of CAV. The area under the curve and accuracy indicators were calculated to evaluate the performance and best cutoffs of CCTA predictors of CAV. RESULTS The median interval between CCTA and HTx was 5 years. Among the 37 recipients, 23 (62.2%) were diagnosed with CAV. The integration of diameter stenosis and plaque morphology (including plaque burden at minimum lumen area >42% and percent atheroma volume >23%) at CCTA yielded the highest diagnostic performance (accuracy, 84%; sensitivity, 83%; specificity, 86%). The integration of ∆fractional flow reserve derived from coronary computed tomography trans-vessel gradient led to increased sensitivity, albeit with decreased specificity and overall accuracy. The noninvasive approach was associated with a lower contrast and radiation dose, compared with the invasive approach. CONCLUSIONS A noninvasive strategy based on CCTA is accurate for managing patients with HTx. CCTA might be considered the preferred imaging modality for annual CAV surveillance after the first year post-HTx.
Collapse
Affiliation(s)
- Marta Belmonte
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
- Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (M. Belmonte, M.M.V., G.E., A.L.)
| | - Pasquale Paolisso
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Galeazzi Sant'Ambrogio, Department of Biomedical and Clinical Sciences, University of Milan, Italy (P.P., E.G.)
| | - Michele Mattia Viscusi
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
- Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (M. Belmonte, M.M.V., G.E., A.L.)
| | - Monika Beles
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Luca Bergamaschi
- Cardiology Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
- Department of Medical and Surgical Sciences, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, University of Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
| | - Angelo Sansonetti
- Cardiology Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
- Department of Medical and Surgical Sciences, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, University of Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
| | - Hirofumi Ohashi
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Ruiko Seki
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Emanuele Gallinoro
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Galeazzi Sant'Ambrogio, Department of Biomedical and Clinical Sciences, University of Milan, Italy (P.P., E.G.)
| | - Giuseppe Esposito
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
- Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (M. Belmonte, M.M.V., G.E., A.L.)
| | - Monika Shumkova
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Attilio Leone
- Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy (M. Belmonte, M.M.V., G.E., A.L.)
| | - Marco Masetti
- Cardiology Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
- Department of Medical and Surgical Sciences, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, University of Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
| | - Emanuele Barbato
- Department of Clinical and Molecular Medicine, Sapienza University of Rome. Cardiology Unit, Sant'Andrea University Hospital, Rome, Italy (E.B.)
| | | | - Riet Dierckx
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Ward Heggermont
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Jan Van Keer
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Luciano Potena
- Cardiology Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
- Department of Medical and Surgical Sciences, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, University of Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
| | - Carmine Pizzi
- Cardiology Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
- Department of Medical and Surgical Sciences, Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, University of Bologna, Italy (L.B., A.S., M.M., L.P., C.P.)
| | - Jozeph Bartunek
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| | - Marc Vanderheyden
- Cardiovascular Center Aalst, Onze-Lieve-Vrouwziekenhuis (OLV) Clinic, Aalst, Belgium (M. Belmonte, P.P., M.M.V., M. Beles, H.O., R.S., G.E., M.S., R.D., W.H., J.V.K., J.B., M.V.)
| |
Collapse
|
|
4
|
Orban M, Kuehl A, Pechmajou L, Müller C, Sfeir M, Brunner S, Braun D, Hausleiter J, Bories MC, Martin AC, Ulrich S, Dalla Pozza R, Mehilli J, Jouven X, Hagl C, Karam N, Massberg S. Reduction of Cardiac Allograft Vasculopathy by PCI: Quantification and Correlation With Outcome After Heart Transplantation. J Card Fail 2024; 30:1222-1230. [PMID: 39389730 DOI: 10.1016/j.cardfail.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Percutaneous coronary intervention (PCI) might improve outcome at severe stages of cardiac allograft vasculopathy (CAV) among patients after heart transplantation (HTx). Yet, risk stratification of HTx patients after PCI remains challenging. AIMS To assess whether the International Society for Heart and Lung Transplantation (ISHLT) CAV classification remains prognostic after PCI and whether risk-stratification models of non-transplanted patients extend to HTx patients with CAV. METHODS At 2 European academic centers, 203 patients were stratified in cohort 1 (ISHLT CAV1, without PCI, n = 126) or cohort 2 (ISHLT CAV2 and 3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I, SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). RSXS-I > 0 defined incomplete revascularization (IR). RESULTS SXS-II predicted mortality in cohort 1 (P = 0.004), whereas SXS-I (P = 0.009) and SXS-II (P = 0.002) predicted mortality in cohort 2. Post-PCI, IR (P = 0.004), high rISHLT (P = 0.02) and highest tertile of rSXS-II (P = 0.006) were associated with higher 5-year mortality. In bivariable Cox analysis, baseline SXS-II, IR and rSXS-II remained predictors of 5-year mortality post-PCI. There was a strong inverse relationship between baseline and rSXS-I (r = -0.55; P < 0.001 and r = -0.50; P = 0.003, respectively) regarding the interval to first reintervention. CONCLUSION People with ISHLT CAV classification could apply for risk stratification after PCI. SYNTAX scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV.
Collapse
Affiliation(s)
- Madeleine Orban
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany.
| | - Anne Kuehl
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Louis Pechmajou
- Department of Cardiology, European Hospital Georges Pompidou, Paris, France; Université Paris Cité, INSERM UMRS-970, Paris Cardiovascular Research Center, Paris, France
| | - Christoph Müller
- Department of Heart Surgery, University Hospital, LMU Munich, Germany
| | - Maroun Sfeir
- Department of Cardiology, European Hospital Georges Pompidou, Paris, France
| | - Stefan Brunner
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Daniel Braun
- Department of Medicine I, University Hospital, LMU Munich, Germany
| | - Joerg Hausleiter
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Marie-Cécile Bories
- Department of Cardiology, European Hospital Georges Pompidou, Paris, France; Université Paris Cité, INSERM UMRS-970, Paris Cardiovascular Research Center, Paris, France
| | - Anne-Céline Martin
- Department of Cardiology, European Hospital Georges Pompidou, Paris, France; Université Paris Cité, INSERM UMRS-1140, Innovative Therapies in Hemostasis, Paris, France
| | - Sarah Ulrich
- Department of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Germany
| | - Robert Dalla Pozza
- Department of Pediatric Cardiology and Intensive Care Medicine, University Hospital, LMU Munich, Germany
| | - Julinda Mehilli
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Xavier Jouven
- Université Paris Cité, INSERM UMRS-970, Paris Cardiovascular Research Center, Paris, France
| | - Christian Hagl
- Department of Heart Surgery, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| | - Nicole Karam
- Department of Cardiology, European Hospital Georges Pompidou, Paris, France; Université Paris Cité, INSERM UMRS-970, Paris Cardiovascular Research Center, Paris, France
| | - Steffen Massberg
- Department of Medicine I, University Hospital, LMU Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Berlin, Germany
| |
Collapse
|
|
5
|
Alcici-Moreira AM, Vitarelli MO, Velloso TA, Carvalho-Ribeiro IA, Dario DM, Polese JC, Guimarães HP, Pena JLB, Tuesta M, de Rezende BA, Rodrigues-Machado MDG. Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study. Sci Rep 2024; 14:10504. [PMID: 38714788 PMCID: PMC11076511 DOI: 10.1038/s41598-024-61152-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 05/02/2024] [Indexed: 05/10/2024] Open
Abstract
We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.
Collapse
Affiliation(s)
- Adriana Marques Alcici-Moreira
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Marcela Oliveira Vitarelli
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Tiago Abreu Velloso
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Igor Antônio Carvalho-Ribeiro
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Daniella Moura Dario
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | | | | | - José Luiz Barros Pena
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Marcelo Tuesta
- Exercise and Rehabilitation Sciences Laboratory, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, Santiago, Chile
| | - Bruno Almeida de Rezende
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil
| | - Maria da Glória Rodrigues-Machado
- Post-Graduate Program in Health Sciences of Medical Sciences Faculty of Minas Gerais (FCM-MG), Alameda Ezequiel Dias, 275, Belo Horizonte, MG, 30130-110, Brazil.
| |
Collapse
|
|
6
|
Shahandeh N, Parikh RV. Invasive Intracoronary Imaging of Cardiac Allograft Vasculopathy: Established Modalities and Emerging Technologies. Interv Cardiol Clin 2023; 12:269-280. [PMID: 36922067 DOI: 10.1016/j.iccl.2022.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Despite advances in the care of heart transplant recipients during the past 5 decades, cardiac allograft vasculopathy (CAV) continues to be a major barrier to long-term survival. The early diagnosis and treatment of CAV is crucial for improving long-term outcomes. Coronary angiography, the current gold standard for CAV screening, has low sensitivity for detecting early CAV. Increasingly, invasive intracoronary imaging modalities that provide a more detailed analysis of vessel anatomy and allow for plaque characterization are being used to detect CAV earlier after transplant and uncover mechanistic insights. Studies validating these emerging imaging platforms are needed before their widespread adoption.
Collapse
Affiliation(s)
- Negeen Shahandeh
- Division of Cardiology, University of California, 100 Medical Plaza, Suite 630 East, Los Angeles, CA 90095, USA
| | - Rushi V Parikh
- Division of Cardiology, University of California, Los Angeles, 100 Medical Plaza, Suite 630 West, Los Angeles, CA 90095, USA.
| |
Collapse
|
|
7
|
Research Highlights. Transplantation 2022. [DOI: 10.1097/tp.0000000000004272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
8
|
Shahandeh N, Kashiyama K, Honda Y, Nsair A, Ali ZA, Tobis JM, Fearon WF, Parikh RV. Invasive Coronary Imaging Assessment for Cardiac Allograft Vasculopathy: State-of-the-Art Review. JOURNAL OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY & INTERVENTIONS 2022; 1:100344. [PMID: 39131933 PMCID: PMC11307976 DOI: 10.1016/j.jscai.2022.100344] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/07/2022] [Accepted: 04/17/2022] [Indexed: 08/13/2024]
Abstract
Heart transplantation is the standard of care treatment for end-stage heart failure. Therapeutic advances including enhanced immunosuppression and aggressive infectious prophylaxis have led to increased life-expectancy following transplantation; however, cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality. Although coronary angiography is the current guideline-recommended diagnostic modality for invasive CAV screening, it is limited in its ability to detect early and/or diffuse disease. Efforts to improve outcomes for heart transplant recipients with CAV have focused on developing diagnostic tools with greater sensitivity to capture early CAV in order to better understand the pathobiology and implement treatment to slow disease progression sooner after transplant. The contemporary invasive imaging armamentarium for CAV surveillance includes coronary angiography, intravascular ultrasound, and newer technologies including optical coherence tomography and near-infrared spectroscopy. The present review outlines the use of and data in support of these imaging platforms in the CAV arena and highlights the potential advantages and limitations of each of these modalities.
Collapse
Affiliation(s)
- Negeen Shahandeh
- Division of Cardiology, University of California Los Angeles, Los Angeles, California
| | - Kuninobu Kashiyama
- Division of Cardiovascular Medicine, Stanford University, Stanford, California
| | - Yasuhiro Honda
- Division of Cardiovascular Medicine, Stanford University, Stanford, California
| | - Ali Nsair
- Division of Cardiology, University of California Los Angeles, Los Angeles, California
| | - Ziad A. Ali
- DeMatteis Cardiovascular Institute, St Francis Hospital & Heart Center, Roslyn, New York
- Cardiovascular Research Foundation, New York, New York
| | - Jonathan M. Tobis
- Division of Cardiology, University of California Los Angeles, Los Angeles, California
| | - William F. Fearon
- Division of Cardiovascular Medicine, Stanford University and VA Palo Alto Health Care Systems, Stanford, California
| | - Rushi V. Parikh
- Division of Cardiology, University of California Los Angeles, Los Angeles, California
| |
Collapse
|
|
9
|
Shiraki T, Ichibori Y, Ohtani T, Mizote I, Kioka H, Tsukamoto Y, Nakamura D, Yokoi K, Ide S, Nakamoto K, Takeda Y, Kotani JI, Hikoso S, Sawa Y, Sakata Y. Pathophysiological Evaluations of Initial Plaque Development After Heart Transplantation via Serial Multimodality Imaging and Cytokine Assessments. J Heart Lung Transplant 2022; 41:877-885. [DOI: 10.1016/j.healun.2022.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 02/14/2022] [Accepted: 03/08/2022] [Indexed: 10/18/2022] Open
|
|
10
|
Analysis of Fibrotic Plaques in Angiographic Manifest Cardiac Allograft Vasculopathy in Long-term Heart Transplanted Patients Using Optical Coherence Tomography. Transplant Direct 2021; 8:e1266. [PMID: 34966839 PMCID: PMC8710340 DOI: 10.1097/txd.0000000000001266] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 12/02/2022] Open
Abstract
Supplemental Digital Content is available in the text. Background. The development and progression of cardiac allograft vasculopathy documented by coronary angiography (CAVangio) after heart transplantation (HTx) has prognostic relevance. Yet there are limited data regarding the role of concomitant intracoronary imaging in the presence CAVangio. In particular, atherosclerotic plaques might represent a potential target for prevention, but their impact on stenosis is understudied. Methods. We used high-resolution intracoronary optical coherence tomography (OCT) to quantify and compare findings of intimal hyperplasia (IH) and plaque morphologies in HTx patients (fibrotic plaque, lipid plaque, and calcified plaque). OCT findings were related to the presence of CAVangio as well as to the severity of stenosis. Results. We included 65 consecutive patients into analysis (66% with CAVangio, posttransplant interval 9.9 ± 7.6 y). Fibrotic, lipid, and calcified plaques were present in 41 (63.1%), 39 (60%), and 18 (27.7%) patients, respectively. In addition to IH, the presence of fibrotic, lipid, and calcified plaques was found to be associated with CAVangio. The prevalence of lipid plaque and quantitative measurements of fibrotic plaque increased with stenosis severity (lipid plaque, P < 0.001, maximal and mean fibrotic arc, P = 0.05 and P = 0.001, respectively). Receiver operating characteristic analysis showed that area under the curve of the fibrotic plaque parameter mean fibrotic arc (0.87, 95% confidence interval [0.76-0.99]; P = 0.002) was superior to area under the curve of intima parameters regarding CAVangio. The effect of mean fibrotic arc (r = 0.52, P < 0.001) was relevant regarding stenosis severity. Conclusions. After a longer posttransplant interval, CAV findings in OCT included a combination of IH and atherosclerotic plaques. In addition to IH, the presence of fibrotic, lipid, and calcified plaques is associated with CAVangio. Further studies are warranted to evaluate if the in vivo screening for plaque progress, particularly of fibrotic plaque, could improve individual secondary prevention and outcome in HTx patients.
Collapse
|
|
11
|
Just IA, Guelfirat M, Leser L, Uecertas A, Kopp Fernandes L, Godde M, Merke N, Stawowy P, Hennig F, Knosalla C, Falk V, Knierim J, Schoenrath F. Diagnostic and Prognostic Value of a TDI-Derived Systolic Wall Motion Analysis as a Screening Modality for Allograft Rejection after Heart Transplantation. Life (Basel) 2021; 11:life11111206. [PMID: 34833082 PMCID: PMC8622239 DOI: 10.3390/life11111206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/04/2021] [Accepted: 11/07/2021] [Indexed: 12/05/2022] Open
Abstract
Background: Despite the risk for complications, allograft surveillance after orthotopic heart transplantation (OHT) is performed by cardiac catheterization and biopsies. We investigated the diagnostic and prognostic value of a TDI-derived systolic wall motion analysis of the posterobasal wall of the left ventricle (Sm) as a screening modality in OHT aftercare. Methods: We examined data of 210 eligible patients who underwent OHT between 2010 and 2020. Forty-four patients who had died within the initial hospital stay were excluded. For 166 patients, baseline and follow-up data were analyzed. The mean age at OHT was 46.2 (±11.4) years; 76.5% were male. Results: Within the observational period, 22 (13.3%) patients died. In total, 170 episodes of acute cellular or humoral rejections occurred (84 ISHLT1R; 13 ISHLT2R; 8 ISHLT3R; 65 AMR), and 29 catheterizations revealed cardiac allograft vasculopathy (5 CAV1; 4 CAV2; 20 CAV3). Individual Sm radial/longitudinal remained stable within the follow-up period (11.5 ± 2.2 cm/s; 10.9 ± 2.1 cm/s). Patients with acute rejections and CAV3 showed significant Sm radial/longitudinal reductions (AMR1: 1.6 ± 1.9 cm/s, confidence interval (CI) 0.77–0.243, p < 0.001; 1.8 ± 2.0 cm/s, CI 0.92–0.267, p < 0.001. ISHLT1R: 1.7 ± 1.8 cm/s, CI 1.32–2.08, p < 0.001; 2.0 ± 1.6 cm/s, CI 1.66–2.34, p < 0.001. CAV3: 1.3 ± 2.5 cm/s, CI 0.23–2.43, p < 0.017; 1.4 ± 2.8 cm/s, CI 0.21–2.66, p < 0.021). Lower Sm was associated with a threefold increase in all-cause mortality (hazard ratio (HR) 3.24, CI 1.2–8.76, p = 0.020; HR 2.92, CI 1.19–7.18, p = 0.019). Overall, Sm-triggered surveillance led to 0.75 invasive diagnostics per patient post-OHT year. Conclusions: Sm remained stable in the post-OHT course. Reductions indicated ISHLT1R, AMR1 and CAV3 and were associated with higher all-cause mortality. Sm-triggered surveillance may be referred to as a safe, high-yield screening modality in OHT aftercare.
Collapse
Affiliation(s)
- Isabell A. Just
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
- Correspondence:
| | - Meryem Guelfirat
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Laura Leser
- Department of Anesthesiology, German Heart Center Berlin, 13353 Berlin, Germany;
| | - Ata Uecertas
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Laurenz Kopp Fernandes
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Maren Godde
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Nicolas Merke
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Philipp Stawowy
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
- Department of Cardiology and Internal Medicine, German Heart Center Berlin, 13353 Berlin, Germany
| | - Felix Hennig
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
| | - Christoph Knosalla
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
| | - Volkmar Falk
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
- Department of Cardiothorarcic Surgery, Charité, Corpoate Member of Freie Universität Berlin, Humboldt-Universitüt Berlin and Berlin Institute of Health, 13353 Berlin, Germany
- Translational Cardiovascular Technologies, Department of Health Sciences, Eidgenoessische Technische Hochschule (ETH) Zurich, 8092 Zurich, Switzerland
| | - Jan Knierim
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
| | - Felix Schoenrath
- Department of Cardiothoracic and Vascular Surgery, German Heart Center Berlin, 13353 Berlin, Germany; (M.G.); (A.U.); (L.K.F.); (M.G.); (N.M.); (F.H.); (C.K.); (V.F.); (J.K.); (F.S.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany;
| |
Collapse
|
|
12
|
Ortega-Legaspi JM, Bravo PE. Diagnosis and management of cardiac allograft vasculopathy. Heart 2021; 108:586-592. [PMID: 34340994 DOI: 10.1136/heartjnl-2020-318063] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 07/07/2021] [Indexed: 11/04/2022] Open
Abstract
One of the main causes of death beyond the first year after heart transplantation is cardiac allograft vasculopathy (CAV). This review summarises the current understanding of its complex pathophysiology, detection and treatment, including the available data on non-invasive imaging modalities used for screening and diagnosis. A better understanding of this entity is crucial to improving the long-term outcomes of the growing population of patients with a heart transplant.
Collapse
Affiliation(s)
- Juan M Ortega-Legaspi
- Department of Medicine, Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Paco E Bravo
- Department of Medicine, Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.,Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
13
|
(Cardiac allograft vasculopathy nowadays). COR ET VASA 2021. [DOI: 10.33678/cor.2020.105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
14
|
Fluschnik N, Geelhoed B, Becher PM, Schrage B, Brunner FJ, Knappe D, Bernhardt AM, Blankenberg S, Kobashigawa J, Reichenspurner H, Schnabel RB, Magnussen C. Non-immune risk predictors of cardiac allograft vasculopathy: Results from the U.S. organ procurement and transplantation network. Int J Cardiol 2021; 331:57-62. [PMID: 33571561 DOI: 10.1016/j.ijcard.2021.02.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 12/31/2020] [Accepted: 02/04/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients. METHODS 40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients' CAV risk. Analyses were based on OPTN data (June 30, 2019). RESULTS Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p < 0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%. CONCLUSIONS In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk.
Collapse
Affiliation(s)
- Nina Fluschnik
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany
| | - Bastiaan Geelhoed
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany
| | - Peter Moritz Becher
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Benedikt Schrage
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany
| | - Fabian J Brunner
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Dorit Knappe
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Alexander M Bernhardt
- Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Stefan Blankenberg
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany
| | - Jon Kobashigawa
- Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Hermann Reichenspurner
- Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Renate B Schnabel
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany
| | - Christina Magnussen
- Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Germany.
| |
Collapse
|
|
15
|
Long B, Brady WJ, Gragossian A, Koyfman A, Gottlieb M. A primer for managing cardiac transplant patients in the emergency department setting. Am J Emerg Med 2021; 41:130-138. [PMID: 33440325 DOI: 10.1016/j.ajem.2020.12.071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/26/2020] [Accepted: 12/27/2020] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Cardiac transplant is an effective long-term management option for several severe cardiac diseases. These cardiac transplant patients may present to the emergency department with a range of issues involving the cardiac transplantation, including complications due to their transplant as well as altered presentations of disease resulting from their transplant. OBJECTIVE This narrative review provides a focused guide to the evaluation and management of patients with cardiac transplantation and its complications. DISCUSSION Cardiac transplant is an effective therapy for end-stage heart failure. A transplanted heart varies both anatomically and physiologically from a native heart. Several significant complications may occur. Graft failure, rejection, and infection are common causes of morbidity and mortality within the first year of transplant. As these patients are on significant immunosuppressive medication regimens, they are at risk of infection, but inadequate immunosuppression increases the risk of acute rejection. A variety of dysrhythmias such as atrial fibrillation and ventricular dysrhythmias may occur. These patients are also at risk of acute coronary syndrome, cardiac allograft vasculopathy, and medication adverse events. Importantly, patients with acute coronary syndrome can have an altered presentation with the so-called "painless" myocardial infarction. Consultation with the transplant physician is recommended, if available, for these patients to assist in evaluation and management. CONCLUSIONS An understanding of the presentations and various complications that may affect patients with cardiac transplant will assist emergency clinicians in the care of these patients.
Collapse
Affiliation(s)
- Brit Long
- Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, TX, United States of America.
| | - William J Brady
- Department of Emergency Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
| | - Alin Gragossian
- The Mt Sinai Hospital, Institute for Critical Care Medicine, New York, NY, United States of America
| | - Alex Koyfman
- Department of Emergency Medicine, UT Southwestern, Dallas, TX, United States of America
| | - Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL, United States of America
| |
Collapse
|
|
16
|
Donor specific anti-HLA antibodies and cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis. Transpl Immunol 2020; 65:101340. [PMID: 33069814 DOI: 10.1016/j.trim.2020.101340] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 10/12/2020] [Accepted: 10/12/2020] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Recent studies suggested potential positive correlations between HLA-specific antibodies and development of cardiac allograft vasculopathy (CAV). METHODS This prospective two-center study investigated early progression of CAV by coronary optical coherence tomography in 1 month and 12 months after heart transplantation (HTx) in 104 patients. Detection and characterization of donor specific (DSA) and MHC class-I polypeptide-related sequence A (MICA) antibodies were performed before, 1, 6 and 12 months after transplantation. RESULTS During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area (P < .001), and progression in mean intimal thickness (IT) (P < .001). DSA and anti-MICA occurred in 17% of all patients, but no significant relationship was observed between presence of DSA/anti-MICA and IT progression within 12 months after HTx. In contrast, we observed significant association between presence of DSA (p=0.031), de-novo DSA (p=0.031), HLA Class II DSA (p=0.017) and media thickness (MT) progression. CONCLUSION Results of our study did not identify a direct association between presence of DSA/anti-MICA and intimal thickness progression in an early period after HTx. However, we found significant relationships between DSA and media thickness progression that may identify a newly recognized immune-pathological aspect of CAV.
Collapse
|
|
17
|
Bobi J, Garabito M, Solanes NÚ, Cidad P, Ramos-Pérez V, Ponce A, Rigol M, Freixa X, Pérez-Martínez C, Pérez de Prado A, Fernández-Vázquez F, Sabaté M, Borrós S, López-López JR, Pérez-García MT, Roqué M. Kv1.3 blockade inhibits proliferation of vascular smooth muscle cells in vitro and intimal hyperplasia in vivo. Transl Res 2020; 224:40-54. [PMID: 32522668 DOI: 10.1016/j.trsl.2020.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/29/2020] [Accepted: 06/01/2020] [Indexed: 11/16/2022]
Abstract
The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in 2 porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. The therapeutic potential of PAP-1 was then evaluated in vivo in swine models of ISR and AV. At 15-days follow-up, morphometric analysis demonstrated a substantial reduction of luminal stenosis in the allografts treated with PAP-1 (autograft 2.72 ± 1.79 vs allograft 10.32 ± 1.92 vs allograft + polymer 13.54 ± 8.59 vs allograft + polymer + PAP-1 3.06 ± 1.08 % of luminal stenosis; P = 0.006) in the swine model of femoral artery transplant. In the pig model of coronary ISR, using a prototype of PAP-1-eluting stent, no differences were observed regarding % of stenosis compared to control stents (31 ± 13 % vs 37 ± 18%, respectively; P = 0.372) at 28-days follow-up. PAP-1 treatment was safe and did not impair vascular healing in terms of delayed endothelialization, inflammation or thrombosis. However, an incomplete release of PAP-1 from stents was documented. We conclude that the use of selective Kv1.3 blockers represents a promising therapeutic approach for the prevention of intimal hyperplasia in AV, although further studies to improve their delivery method are needed to elucidate its potential in ISR.
Collapse
Affiliation(s)
- Joaquim Bobi
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Manel Garabito
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - NÚria Solanes
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Pilar Cidad
- Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and CSIC, Valladolid, Spain
| | - Víctor Ramos-Pérez
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Barcelona, Spain
| | - Alberto Ponce
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Barcelona, Spain
| | - Montserrat Rigol
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Xavier Freixa
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Claudia Pérez-Martínez
- Grupo Cardiovascular (HemoLeon), Fundación Investigación Sanitaria en León y del Instituto de Biomedicina (IBIOMED), Universidad de León, Hospital Universitario de León, León, Spain
| | - Armando Pérez de Prado
- Grupo Cardiovascular (HemoLeon), Fundación Investigación Sanitaria en León y del Instituto de Biomedicina (IBIOMED), Universidad de León, Hospital Universitario de León, León, Spain
| | - Felipe Fernández-Vázquez
- Grupo Cardiovascular (HemoLeon), Fundación Investigación Sanitaria en León y del Instituto de Biomedicina (IBIOMED), Universidad de León, Hospital Universitario de León, León, Spain
| | - Manel Sabaté
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Salvador Borrós
- Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Barcelona, Spain; CIBER of Biomaterials Bioengineering and Nanomedicine (CIBER-BBN), Barcelona, Spain
| | - José Ramón López-López
- Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and CSIC, Valladolid, Spain
| | - Mª Teresa Pérez-García
- Departamento de Bioquímica y Biología Molecular y Fisiología and Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and CSIC, Valladolid, Spain
| | - MercÈ Roqué
- Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS) and Cardiology Department, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
| |
Collapse
|
|
18
|
Habibi S, Ghaffarpasand E, Shojaei F, Alihashemi M, Kahe F, Zahedi Tajrishi F, Chi G. Prognostic Value of Biomarkers in Cardiac Allograft Vasculopathy following Heart Transplantation: A Literature Review. Cardiology 2020; 145:693-702. [PMID: 32892195 DOI: 10.1159/000509630] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 06/23/2020] [Indexed: 11/19/2022]
Abstract
Cardiac allograft vasculopathy (CAV), also known as cardiac transplant vasculopathy, is a major determinant of long-term survival among cardiac transplantation recipients. Histologically, CAV is featured by diffuse, concentric thickening of the vascular wall, and primarily affects large and small epicardial coronary arteries, intramyocardial arteries, and veins. Owing to graft denervation, CAV typically follows an insidious course, and patients may not experience classic angina symptoms but instead present with progressive heart failure or ventricular arrhythmias. Recent studies on biomarkers have furthered the knowledge concerning the prediction and prognosis of CAV. Given its association with metabolic, thrombotic, inflammatory, and immunologic markers, CAV is likely to represent a complex multifactorial process that involves both immune-mediated and non-immune-mediated pathways. In order to identify the high-risk patients that would benefit from early intervention, future research is warranted to examine the usefulness of a biomarker panel in CAV risk stratification.
Collapse
Affiliation(s)
- Shaghayegh Habibi
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Eiman Ghaffarpasand
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Fahimehalsadat Shojaei
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Mahda Alihashemi
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Farima Kahe
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Gerald Chi
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA,
| |
Collapse
|
|
19
|
Vessel Fractional Flow Reserve and Graft Vasculopathy in Heart Transplant Recipients. J Interv Cardiol 2020; 2020:9835151. [PMID: 32733172 PMCID: PMC7376430 DOI: 10.1155/2020/9835151] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/12/2020] [Indexed: 11/18/2022] Open
Abstract
Background Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. Purpose The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. Methods In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. Results In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p = 0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). Conclusion The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.
Collapse
|
|
20
|
Garekar S, Meeran T, Patel V, Patil S, Dhake S, Mali S, Mhatre A, Bind D, Gaur A, Sinha S, Shetty V, Sabnis K, Soni B, Malankar D, Mulay A. Early experience with pediatric cardiac transplantation in a limited resource setting. Ann Pediatr Cardiol 2020; 13:220-226. [PMID: 32863657 PMCID: PMC7437633 DOI: 10.4103/apc.apc_105_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 03/23/2020] [Accepted: 05/21/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Pediatric heart transplantation is a now a well-established and standard treatment option for end stage heart failure for various conditions in children. Due to logistic issues, it is not an option for in most pediatric cardiac centres in the third world. AIM We sought to describe our early experience in the current era in India. METHODS This is a short term retrospective chart review of pediatric patients who underwent heart transplantation at our centre. Mean/Median with standard deviation /range was used to present data. RESULTS Twenty patients underwent orthotopic heart transplant between January 2016 and June 2019. The median age at transplant was 12.4years (range 3.3 to 17.3 years). The median weight was 23.2kg (range 10-80kg). The mean donor/recipient weight ratio was 1.62± 0.84. The mean ICU stay was 12.1days. The mean follow up post transplant was 2.03± 0.97years (range 10 days-3.57years). The 1 month and the 1 year survival was 100%. Biopsies were positive for significant rejection in 7 patients (35%). At the time of last follow-up, 3 patients (15%) had expired. The major post transplant morbidities were mechanical circulatory support (n=3), hypertension with seizure complex (n=3), post transplant lympho-proliferative disorder (n=1), pseudocyst of pancreas (n=1), coronary allograft vasculopathy (n=3) and systemic hypertension (n=7). All surviving patients (n=17) were asymptomatic at last follow up. CONCLUSION The results suggest acceptable short term outcomes in Indian pediatric patients can be achieved after heart transplantation in the current era. Significant rejection episodes and coronary allograft vasculopathy need careful follow up.
Collapse
Affiliation(s)
- Swati Garekar
- Division of Pediatric Cardiology, Fortis Hospital, Mumbai, Maharashtra, India
| | - Talha Meeran
- Division of Advanced Heart Failure, Cardiac Transplant and Pulmonary Hypertension, Fortis Hospital, Mumbai, Maharashtra, India
| | - Vinay Patel
- Division of Pediatric Cardiology, Fortis Hospital, Mumbai, Maharashtra, India
| | - Sachin Patil
- Division of Pediatric Anesthesiology and Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Shyam Dhake
- Division of Pediatric Anesthesiology and Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Shivaji Mali
- Division of Pediatric Anesthesiology and Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Amit Mhatre
- Division of Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Dilip Bind
- Division of Intensive Care, Fortis Hospital, Mumbai, Maharashtra, India
| | - Ashish Gaur
- Division of Cardiothoracic Surgery, Fortis Hospital, Mumbai, Maharashtra, India
| | - Sandeep Sinha
- Division of Cardiothoracic Surgery, Fortis Hospital, Mumbai, Maharashtra, India
| | - Vijay Shetty
- Division of Anesthesiology, Fortis Hospita, Mumbai, Maharashtra, India
| | - Kirtis Sabnis
- Division of Infectious Diseases, Fortis Hospital, Mumbai, Maharashtra, India
| | - Bharat Soni
- Division of Pediatric Cardiothoracic Surgery, Fortis Hospital, Mumbai, Maharashtra, India
| | - Dhananjay Malankar
- Division of Pediatric Cardiothoracic Surgery, Fortis Hospital, Mumbai, Maharashtra, India
| | - Anvay Mulay
- Division of Cardiothoracic Surgery, Fortis Hospital, Mumbai, Maharashtra, India
| |
Collapse
|
|
21
|
The role of optical coherence tomography and other intravascular imaging modalities in cardiac allograft vasculopathy. ADVANCES IN INTERVENTIONAL CARDIOLOGY 2020; 16:19-29. [PMID: 32368233 PMCID: PMC7189132 DOI: 10.5114/aic.2020.93909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/13/2020] [Indexed: 11/17/2022] Open
Abstract
Orthotopic heart transplantation (OHT) is the standard-of-care for end-stage heart disease. Although a significant improvement in the prognosis of patients after OHT has been observed in recent years, their overall mortality remains relatively high, with a median survival of approximately 10 years after transplantation. One of the primary causes of death in patients after OHT is cardiac allograft vasculopathy (CAV), the condition developing specifically in the coronary vasculature after OHT, the pathophysiology of which is still inadequately known. It is estimated that CAV development and progression is responsible for approximately 30% of deaths within five years post-OHT. According to the International Society for Heart and Lung Transplantation (ISHLT) Nomenclature for CAV, its presence should be assessed primarily by the coronary angiography performed routinely after OHT, mostly due to its wide availability, reproducibility, and low complication rate. However, the analysis of CAV in coronary angiography has limitations, mostly concerning its - sometimes inadequate - sensitivity and specificity. Hence, there is a growing need for the introduction of more accurate methods of CAV assessment, such as intravascular imaging, which through a thorough evaluation of the arterial wall structure and thickness allows the drawbacks of routine angiography to be minimised. The aim of the article was to critically summarise the current findings derived from the analysis of CAV by optical coherence tomography, the other intravascular imaging modalities, such as intravascular ultrasound (IVUS) and IVUS-derived virtual histology, along with physiological assessment with the use of the fractional flow reserve.
Collapse
|
|
22
|
Miller RJH, Kwiecinski J, Shah KS, Eisenberg E, Patel J, Kobashigawa JA, Azarbal B, Tamarappoo B, Berman DS, Slomka PJ, Kransdorf E, Dey D. Coronary computed tomography-angiography quantitative plaque analysis improves detection of early cardiac allograft vasculopathy: A pilot study. Am J Transplant 2020; 20:1375-1383. [PMID: 31758640 DOI: 10.1111/ajt.15721] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 10/30/2019] [Accepted: 11/15/2019] [Indexed: 01/25/2023]
Abstract
Cardiac allograft vasculopathy (CAV) is an increasingly important complication after cardiac transplant. We assessed the additive diagnostic benefit of quantitative plaque analysis in patients undergoing coronary computed tomography-angiography (CCTA). Consecutive patients undergoing CCTA for CAV surveillance were identified. Scans were visually interpreted for coronary stenosis. Semiautomated software was used to quantify noncalcified plaque (NCP), as well as its components. Optimal diagnostic cut-offs for CAV, with coronary angiography as gold standard, were defined using receiver operating characteristic curves. In total, 36 scans were identified in 17 patients. CAV was present in 17 (46.0%) reference coronary angiograms, at a median of 1.9 years before CCTA. Median NCP (147 vs 58, P < .001), low-density NCP (median 4.5 vs 0.9, P = .003), fibrous plaque (median 76.1 vs 31.1, P = .003), and fibrofatty plaque (median 63.6 vs 27.6, P < .001) volumes were higher in patients with CAV, whereas calcified plaque was not (median 0.0 vs 0.0, P = .510). Visual assessment of CCTA alone was 70.6% sensitive and 100% specific for CAV. The addition of total NCP volume increased sensitivity to 82.4% while maintaining 100% specificity. NCP volume is significantly higher in patients with CAV. The addition of quantitative analysis to visual interpretation improves the sensitivity for detecting CAV without reducing specificity.
Collapse
Affiliation(s)
- Robert J H Miller
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.,Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jacek Kwiecinski
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.,Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Kevin S Shah
- Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Evann Eisenberg
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jignesh Patel
- Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Jon A Kobashigawa
- Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Babak Azarbal
- Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Balaji Tamarappoo
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Daniel S Berman
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Piotr J Slomka
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Evan Kransdorf
- Smidt Heart Institute, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Damini Dey
- Department of Imaging, Medicine, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| |
Collapse
|
|
23
|
Pyka Ł, Hawranek M, Szyguła-Jurkiewicz B, Desperak P, Szczurek W, Lekston A, Gąsior M, Zembala MO, Pawlak S, Zembala M, Przybyłowski P. Everolimus-Eluting Second-Generation Stents for Treatment of De Novo Lesions in Patients with Cardiac Allograft Vasculopathy. Ann Transplant 2020; 25:e921266. [PMID: 32253369 PMCID: PMC7163333 DOI: 10.12659/aot.921266] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Background Cardiac allograft vasculopathy is a major cause of cardiac allograft rejection. Percutaneous coronary intervention has become the main form of treatment of significant focal lesions. Despite the significance of the problem, data remain scarce. With a large population of transplant recipients undergoing coronary angiography at our center, we decided to analyze the implications of the use of everolimus-eluting second-generation stents by performing 6-month clinical and angiographic follow-up. Material/Methods From December 2012 and August 2019, 319 patients after heart transplantation undergoing coronary angiography at our institution were analyzed. Subsequently, 22 patients underwent de novo angioplasty with second-generation everolimus-eluting stents. The primary study endpoint was angiographic restenosis as evaluated by quantitative coronary angiography. Secondary outcomes included binary restenosis, target lesion revascularization, and cardiac death during the follow-up period (6 months). Results Patient comorbidities included hypertension (77.3%), type 2 diabetes mellitus (68.2%), dyslipidemia (68.2%), and obesity (31.8%). Primary success was obtained in all of the treated lesions. The analysis of quantitative coronary angiography after 6-month follow-up revealed low late lumen loss (0.22±0.40). Significant restenosis was observed in 1 of the cases. There were no deaths in the 6-month observation period. Conclusions In the analyzed population, invasive strategy with second-generation everolimus-eluting stents for de novo lesions in cardiac allograft vasculopathy resulted in a low rate of binary restenosis, low late lumen loss, and no deaths during the 6-month follow-up.
Collapse
Affiliation(s)
- Łukasz Pyka
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Michał Hawranek
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Bożena Szyguła-Jurkiewicz
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Piotr Desperak
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Wioletta Szczurek
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Andrzej Lekston
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Mariusz Gąsior
- Third Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Michał O Zembala
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Szymon Pawlak
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Marian Zembala
- Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Piotr Przybyłowski
- Silesian Center for Heart Diseases, Zabrze, Poland.,First Department of General Surgery, Jagiellonian University, Medical College, Cracow, Poland
| |
Collapse
|
|
24
|
Foldyna B, Sandri M, Luecke C, Garbade J, Gohmann R, Hahn J, Fischer J, Gutberlet M, Lehmkuhl L. Quantitative coronary computed tomography angiography for the detection of cardiac allograft vasculopathy. Eur Radiol 2020; 30:4317-4326. [PMID: 32179995 PMCID: PMC7338811 DOI: 10.1007/s00330-019-06653-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 11/20/2019] [Accepted: 12/19/2019] [Indexed: 12/21/2022]
Abstract
Objectives To associate coronary wall volume and composition, derived from coronary computed tomography angiography (CTA), with cardiac allograft vasculopathy (CAV) detected on invasive coronary angiography (ICA) in heart-transplanted (HTX) patients. Methods We included consecutive adults who received ICA and coronary CTA for evaluation of CAV ≥ 10 months after HTX. In all coronary segments, we assessed lumen and wall volumes and segmental length, calculated volume-length ratio (VLR) (volumes indexed by segmental length; mm3/mm), wall burden (WB) (wall/wall + lumen volumes; %), and assessed proportions of calcified, fibrotic, fibro-fatty, and low-attenuation tissue (%) in coronary wall. We rendered independent CTA measures associated with CAV by ICA, tested their discriminatory capacity, and assessed concordance between CTA and ICA. Results Among 50 patients (84% men; 53.6 ± 11.9 years), we analyzed 632 coronary segments. Mean interval between HTX and CTA was 6.7 ± 4.7 years and between ICA and CTA 1 (0–1) day. Segmental VLR, WB, and proportion of fibrotic tissue were independently associated with CAV (OR = 1.06–1.27; p ≤ 0.002), reaching a high discriminatory capacity (combination of all three: AUC = 0.84; 95%CI, 0.75–0.90). Concordance between CTA and ICA was higher in advanced CAV (88%) compared with that in none (37%) and mild (19%) CAV. Discordance was primarily driven by a large number of segments with coronary wall changes on CTA but without luminal stenoses on ICA (177/591; 25%). Conclusion CTA-derived coronary wall VLR, WB, and the proportion of fibrotic tissue are independent markers of CAV. Combination of these three parameters may aid the detection of early CAV not detected by ICA, the current standard of care. Key Points • Coronary CTA detects CAV in HTX patients. • Coronary wall volume-length ratio, wall burden, and proportion of fibrotic tissue are independently associated with CAV. • In contrast to ICA, coronary CTA may identify the early stages of CAV. Electronic supplementary material The online version of this article (10.1007/s00330-019-06653-3) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Borek Foldyna
- Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany. .,Cardiovascular Imaging Research Center, Massachusetts General Hospital - Harvard Medical School, Boston, MA, USA. .,Clinic for Radiology, Cardiovascular Center Bad Neustadt, Bad Neustadt, Germany.
| | - Marcus Sandri
- Department of Cardiology, University of Leipzig - Heart Center, Leipzig, Germany
| | - Christian Luecke
- Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany
| | - Jens Garbade
- University Department for Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany
| | - Robin Gohmann
- Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany
| | - Jochen Hahn
- University Department for Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany
| | - Julia Fischer
- Department of Cardiology, University of Leipzig - Heart Center, Leipzig, Germany
| | - Matthias Gutberlet
- Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany
| | - Lukas Lehmkuhl
- Department of Interventional and Diagnostic Radiology, University of Leipzig - Heart Center, Struempellstrasse 39, 04289, Leipzig, Germany.,Clinic for Radiology, Cardiovascular Center Bad Neustadt, Bad Neustadt, Germany
| |
Collapse
|
|
25
|
Intravascular Imaging for Assessment of Cardiac Allograft Vasculopathy Following Heart Transplantation. CURRENT CARDIOVASCULAR IMAGING REPORTS 2020. [DOI: 10.1007/s12410-020-9525-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
26
|
Pazdernik M, Wichterle D, Chen Z, Bedanova H, Kautzner J, Melenovsky V, Karmazin V, Malek I, Stiavnicky P, Tomasek A, Ozabalova E, Krejci J, Wahle A, Zhang H, Kovarnik T, Sonka M. Heart rate and early progression of cardiac allograft vasculopathy: A prospective study using highly automated 3-D optical coherence tomography analysis. Clin Transplant 2019; 34:e13773. [PMID: 31859379 DOI: 10.1111/ctr.13773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 12/11/2019] [Accepted: 12/16/2019] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Heart rate slowing agents are frequently prescribed to manage heart transplant (HTx) patients with the assumption that higher heart rate is a risk factor in cardiovascular disease. PATIENTS AND METHODS This prospective two-center study investigated early progression of cardiac allograft vasculopathy (CAV) in 116 HTx patients. Examinations by coronary optical coherence tomography and 24-hour ambulatory ECG monitoring were performed both at baseline (1 month after HTx) and during follow-up (12 months after HTx). RESULTS During the first post-HTx year, we observed a significant reduction in the mean coronary luminal area from 9.0 ± 2.5 to 8.0 ± 2.4 mm2 (P < .001), and progression in mean intimal thickness (IT) from 106.5 ± 40.4 to 130.1 ± 53.0 µm (P < .001). No significant relationship was observed between baseline and follow-up mean heart rates and IT progression (R = .02, P = .83; R = -.13, P = .18). We found a mild inverse association between beta-blocker dosage at 12 months and IT progression (R = -.20, P = .035). CONCLUSION Our study did not confirm a direct association between mean heart rate and progression of CAV. The role of beta blockers warrants further investigation, with our results indicating that they may play a protective role in early CAV development.
Collapse
Affiliation(s)
- Michal Pazdernik
- Department of Cardiology, IKEM, Prague, Czech Republic.,Department of Cardiology, 2nd Medical School, Charles University, University Hospital Motol, Prague, Czech Republic
| | - Dan Wichterle
- Department of Cardiology, IKEM, Prague, Czech Republic.,2nd Department of Internal Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Zhi Chen
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA, USA
| | - Helena Bedanova
- Cardiovascular and Transplantation Surgery, Brno, Czech Republic
| | | | | | | | - Ivan Malek
- Department of Cardiology, IKEM, Prague, Czech Republic
| | | | - Ales Tomasek
- Cardiovascular and Transplantation Surgery, Brno, Czech Republic
| | - Eva Ozabalova
- Department of Cardiovascular Diseases, St. Anne's University Hospital and Masaryk University Brno, Brno, Czech Republic
| | - Jan Krejci
- Department of Cardiovascular Diseases, St. Anne's University Hospital and Masaryk University Brno, Brno, Czech Republic
| | - Andreas Wahle
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA, USA
| | - Honghai Zhang
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA, USA
| | - Tomas Kovarnik
- Department of Cardiology, IKEM, Prague, Czech Republic.,2nd Department of Internal Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Milan Sonka
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA, USA
| |
Collapse
|
|
27
|
Transplant arteriosclerosis in humanized mice reflects chronic lung allograft dysfunction and is controlled by regulatory T cells. J Thorac Cardiovasc Surg 2019; 157:2528-2537. [PMID: 30955963 DOI: 10.1016/j.jtcvs.2019.01.134] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 01/04/2019] [Accepted: 01/06/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n = 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice. METHODS Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4+CD25high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 ± 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 ± 5 months. RESULTS In the PBMC CLAD+ group of mouse experiments, TA was significantly more severe than in the PBMC CLAD- group (39.9% ± 13% vs 14.9% ± 4% intimal thickening; P = .0081). Then, intimal thickening was significantly inhibited in the PBMC+ regulatory T cells CLAD+ group compared with the PBMC CLAD+ group (0.4% ± 4% vs 39.9% ± 13%; P = .003). In the experiments using PBMCs from lung recipients without CLAD, enriching regulatory T cells also suppressed the development of TA (0.9% ± 3% PBMC CLAD- vs 14.9% ± 4% PBMC+ regulatory T cells CLAD-; P = .001). CONCLUSIONS Lung transplant recipients who later develop CLAD have peripheral leukocytes already at the time of transplant that transfer proinflammatory properties leading to TA in a humanized mouse model. TA remains sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention of CLAD after lung transplantation.
Collapse
|
|
28
|
Chen Z, Pazdernik M, Zhang H, Wahle A, Guo Z, Bedanova H, Kautzner J, Melenovsky V, Kovarnik T, Sonka M. Quantitative 3D Analysis of Coronary Wall Morphology in Heart Transplant Patients: OCT-Assessed Cardiac Allograft Vasculopathy Progression. Med Image Anal 2018; 50:95-105. [PMID: 30253306 PMCID: PMC6237624 DOI: 10.1016/j.media.2018.09.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 07/26/2018] [Accepted: 09/05/2018] [Indexed: 01/25/2023]
Abstract
Cardiac allograft vasculopathy (CAV) accounts for about 30% of all heart-transplant (HTx) patient deaths. For patients at high risk for CAV complications after HTx, therapy must be initiated early to be effective. Therefore, new phenotyping approaches are needed to identify such HTx patients at the earliest possible time. Coronary optical coherence tomography (OCT) images were acquired from 50 HTx patients 1 and 12 months after HTx. Quantitative analysis of coronary wall morphology used LOGISMOS segmentation strategy to simultaneously identify three wall-layer surfaces for the entire pullback length in 3D: luminal, outer intimal, and outer medial surfaces. To quantify changes of coronary wall morphology between 1 and 12 months after HTx, the two pullbacks were mutually co-registered. Validation of layer thickness measurements showed high accuracy of performed layer analyses with layer thickness measures correlating well with manually-defined independent standard (Rautomated2 = 0.93, y=1.0x-6.2μm), average intimal+medial thickness errors were 4.98 ± 31.24 µm, comparable with inter-observer variability. Quantitative indices of coronary wall morphology 1 month and 12 months after HTx showed significant local as well as regional changes associated with CAV progression. Some of the newly available fully-3D baseline indices (intimal layer brightness, medial layer brightness, medial thickness, and intimal+medial thickness) were associated with CAV-related progression of intimal thickness showing promise of identifying patients subjected to rapid intimal thickening at 12 months after HTx from OCT-image data obtained just 1 month after HTx. Our approach allows quantification of location-specific alterations of coronary wall morphology over time and is sensitive even to very small changes of wall layer thicknesses that occur in patients following heart transplant.
Collapse
Affiliation(s)
- Zhi Chen
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA 52242, USA
| | - Michal Pazdernik
- Institute of Clinical and Experimental Medicine (IKEM) in Prague, Czech Republic
| | - Honghai Zhang
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA 52242, USA
| | - Andreas Wahle
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA 52242, USA
| | - Zhihui Guo
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA 52242, USA
| | - Helena Bedanova
- Cardiovascular and Transplantation Surgery Center, Department of Cardiovascular Diseases, St. Annes University Hospital and Masaryk University Brno, Czech Republic
| | - Josef Kautzner
- Institute of Clinical and Experimental Medicine (IKEM) in Prague, Czech Republic
| | - Vojtech Melenovsky
- Institute of Clinical and Experimental Medicine (IKEM) in Prague, Czech Republic
| | - Tomas Kovarnik
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague & General University Hospital in Prague, Czech Republic
| | - Milan Sonka
- Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA 52242, USA.
| |
Collapse
|
|
29
|
Pazdernik M, Chen Z, Bedanova H, Kautzner J, Melenovsky V, Karmazin V, Malek I, Tomasek A, Ozabalova E, Krejci J, Franekova J, Wahle A, Zhang H, Kovarnik T, Sonka M. Early detection of cardiac allograft vasculopathy using highly automated 3-dimensional optical coherence tomography analysis. J Heart Lung Transplant 2018; 37:992-1000. [DOI: 10.1016/j.healun.2018.04.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 03/08/2018] [Accepted: 04/03/2018] [Indexed: 11/29/2022] Open
|
|
30
|
Comprehensive morphologic and functional imaging of heart transplant patients: first experience with dynamic perfusion CT. Eur Radiol 2018; 28:4111-4121. [PMID: 29713770 DOI: 10.1007/s00330-018-5436-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/05/2018] [Accepted: 03/16/2018] [Indexed: 12/26/2022]
Abstract
OBJECTIVES We aimed to assess the diagnostic performance of a combined protocol with coronary computed tomography angiography (CCTA) and stress CT perfusion imaging (CTP) in heart transplant patients for comprehensive morphological and functional imaging. METHODS In this prospective study, 13 patients undergoing routine follow-up 8±6 years after heart transplantation underwent CCTA and dynamic adenosine stress CTP using a third-generation dual-source CT scanner, cardiac magnetic resonance (MR) adenosine stress perfusion imaging at 1.5 T, and catheter coronary angiography. In CCTA stenoses >50% luminal diameter narrowing were noted. Myocardial perfusion deficits were documented in CTP and MR. Quantitative myocardial blood flow (MBF) was calculated with CTP. Left ventricular ejection fraction was determined on cardiac MR cine images. Radiation doses of CT were determined. RESULTS One of the 13 patients had to be excluded because of severe motion artifacts. CCTA identified three patients with stenosis >50%, which were confirmed with catheter coronary angiography. CTP showed four patients with stress-induced myocardial hypoperfusion, which were confirmed by MR stress perfusion imaging. Quantitative analysis of global MBF showed lower mean values as compared to known reference values (MBF under stress 125.5 ± 34.5 ml/100 ml/min). Average left ventricular ejection fraction was preserved (56 ± 5%). CONCLUSIONS In heart transplant patients, a comprehensive CT protocol for the assessment of morphology and function including CCTA and CTP showed good concordance to results from MR perfusion imaging and catheter coronary angiography. KEY POINTS • Stress CT perfusion imaging enables the detection of myocardial ischemia • CT myocardial perfusion imaging can be combined with coronary computed tomography angiography • Combining perfusion and coronary CT imaging is accurate in heart transplant patients • CT myocardial perfusion imaging can be performed at a reasonable radiation dose.
Collapse
|
|
31
|
Fearon WF, Felix R, Hirohata A, Sakurai R, Jose PO, Yamasaki M, Nakamura M, Fitzgerald PJ, Valantine HA, Yock PG, Yeung AC. The effect of negative remodeling on fractional flow reserve after cardiac transplantation. Int J Cardiol 2017; 241:283-287. [PMID: 28413112 DOI: 10.1016/j.ijcard.2017.04.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 04/01/2017] [Accepted: 04/07/2017] [Indexed: 11/27/2022]
Abstract
BACKGROUND Negative remodeling is a common occurrence early after cardiac transplantation. Its impact on the development of myocardial ischemia is not well documented. The aim of this study is to investigate the impact of negative remodeling on fractional flow reserve after cardiac transplantation. METHODS Thirty-four cardiac transplant recipients underwent intravascular ultrasound (IVUS) and fractional flow reserve (FFR) assessment soon after transplantation and one year later. Patients were divided into those with and without negative remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients with negative remodeling, there was no significant change in plaque volume (119.3±82.0 to 131.3±91.2mm3, p=0.21), but vessel volume (775.6±212.0 to 621.9±144.1mm3, p<0.0001) and lumen volume (656.3±169.1 to 490.7±132.0mm3, p<0.0001) decreased significantly and FFR likewise decreased significantly (0.88±0.06 to 0.84±0.07, p=0.04). In the 15 patients without negative remodeling, vessel volume did not change (711.7±217.6 to 745.7±198.5, p=0.28), but there was a significant increase in plaque volume (126.8±88.3 to 194.4±92.7, p<0.001) and a resultant significant decrease in FFR (0.89±0.05 to 0.85±0.05, p=0.01). CONCLUSION Negative remodeling itself, without any change in plaque volume can cause a significant decrease in fractional flow reserve after cardiac transplantation and appears to be another possible mechanism for myocardial ischemia.
Collapse
Affiliation(s)
- William F Fearon
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States.
| | - Robert Felix
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Atsushi Hirohata
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Ryota Sakurai
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Powell O Jose
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Masao Yamasaki
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Mamoo Nakamura
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Peter J Fitzgerald
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Hannah A Valantine
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Paul G Yock
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| | - Alan C Yeung
- Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, United States
| |
Collapse
|
|
32
|
Watanabe T, Seguchi O, Yanase M, Fujita T, Murata Y, Sato T, Sunami H, Nakajima S, Kataoka Y, Nishimura K, Hisamatsu E, Kuroda K, Okada N, Hori Y, Wada K, Hata H, Ishibashi-Ueda H, Miyamoto Y, Fukushima N, Kobayashi J, Nakatani T. Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis. Transplantation 2017; 101:1310-1319. [PMID: 27472091 PMCID: PMC5441888 DOI: 10.1097/tp.0000000000001322] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 05/02/2016] [Indexed: 11/26/2022]
Abstract
BACKGROUND The influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear. METHODS We performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx. RESULTS Donor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002). CONCLUSIONS This volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.
Collapse
Affiliation(s)
- Takuya Watanabe
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Osamu Seguchi
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Masanobu Yanase
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Tomoyuki Fujita
- Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Yoshihiro Murata
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
- Department of Cardiology, Kumiai Kosei Hospital, Takayama, Gifu, Japan
| | - Takuma Sato
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Haruki Sunami
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Seiko Nakajima
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Yu Kataoka
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Kunihiro Nishimura
- Department of Preventive Medicine and Epidemiologic Informatics, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Eriko Hisamatsu
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Kensuke Kuroda
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Norihiro Okada
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Yumiko Hori
- Department of Nursing, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Kyoichi Wada
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Hiroki Hata
- Department of Cardiology, Kumiai Kosei Hospital, Takayama, Gifu, Japan
| | - Hatsue Ishibashi-Ueda
- Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Yoshihiro Miyamoto
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Norihide Fukushima
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Junjiro Kobayashi
- Department of Cardiology, Kumiai Kosei Hospital, Takayama, Gifu, Japan
| | - Takeshi Nakatani
- Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| |
Collapse
|
|
33
|
Abstract
PURPOSE OF REVIEW Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Innovative new techniques to diagnose CAV have been applied to detect disease. This review will examine the current diagnostic and treatment options available to clinicians for CAV. RECENT FINDINGS Diagnostic modalities addressing the pathophysiology underlying CAV (arterial wall thickening and decreased coronary blood flow) improve diagnostic sensitivity when compared to traditional (angiography and dobutamine stress echocardiography) techniques. SUMMARY Limited options are available to prevent and treat CAV; however, progress has been made in making an earlier and more accurate diagnosis. Future research is needed to identify the optimal time to modify immunosuppression and investigate novel treatments for CAV.
Collapse
|
|
34
|
Kuehnel M, Maegel L, Vogel-Claussen J, Robertus JL, Jonigk D. Airway remodelling in the transplanted lung. Cell Tissue Res 2016; 367:663-675. [PMID: 27837271 DOI: 10.1007/s00441-016-2529-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 10/12/2016] [Indexed: 12/22/2022]
Abstract
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.
Collapse
Affiliation(s)
- Mark Kuehnel
- Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany.,Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hanover, Germany
| | - Lavinia Maegel
- Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany.,Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), The German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Hanover, Germany
| | | | - Jan Lukas Robertus
- Royal Brompton & Harefield NHS Foundation Trust, Department of Histopathology, Hanover, Germany
| | - Danny Jonigk
- Institute of Pathology, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625, Hanover, Germany.
| |
Collapse
|
|
35
|
|
|
36
|
Comparison Between Cardiac Allograft Vasculopathy and Native Coronary Atherosclerosis by Optical Coherence Tomography. Am J Cardiol 2016; 117:1361-8. [PMID: 26920081 DOI: 10.1016/j.amjcard.2016.01.036] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 01/20/2016] [Accepted: 01/20/2016] [Indexed: 12/20/2022]
Abstract
We sought to explore differences in distribution and morphology of coronary lesions comparing cardiac allograft vasculopathy and native coronary atherosclerosis (NCA) using intravascular imaging with optical coherence tomography (OCT). At the time of routine surveillance angiography, 17 heart transplant (HT) recipients with a history of high-grade cellular rejection (HGR) and 43 HT recipients with none/mild (low)-grade rejection underwent OCT imaging of the left anterior descending and were compared to 60 patients with NCA without HT. Compared with patients with NCA, patients with HGR had similar intima areas but smaller external elastic lamina areas (7.9 mm(2) [6.3, 11.2] versus 6.6 mm(2) [4.8, 7.5], p = 0.02) resulting in smaller lumen areas (4.5 mm(2) [3.4, 6.6] versus 3.3 mm(2) [2.8, 4.7], p = 0.04) in distal segments and smaller lumen diameters in side branches (1.28 mm [1.19, 1.37] versus 1.09 mm [0.94, 1.24], p = 0.04). Compared with patients with NCA, lesions in patients with HT were more homogeneous, involving the entire coronary vascular tree. Patients with HGR had a higher prevalence of macrophages involving ≥1 quadrant in all 3 segments compared with patients with NCA. The number of microvessels was greater in patients with both HGR and LGR HT versus NCA. In conclusion, distinct findings in the distribution and morphology of coronary lesions between HT recipients and patients with NCA are evident by OCT imaging, suggesting that OCT might be useful to help differentiate cardiac allograft vasculopathy from NCA in vivo.
Collapse
|
|
37
|
Abstract
BACKGROUND Chronic rejection leading to allograft loss remains a significant concern after facial allotransplantation. Chronic rejection may occur without clinical signs or symptoms. The current means of monitoring is histologic analyses of allograft biopsy specimens, which is both invasive and impractical. Prior data suggest that chronic rejection is associated with changes in intima and media thickness of vessels in arms and solid organ allografts; such data have not been published for face transplant recipients. METHODS The authors used a 48-MHz transducer to acquire images of the bilateral facial, radial, dorsalis pedis and, if applicable, sentinel flap arteries in five face transplant recipients (8 months to 4.5 years after transplantation) and five control subjects. The authors assessed the intima, media, and adventitia thickness plus lumen and the total vessel diameter and area. RESULTS Face transplant recipients had thicker intima in all sites compared with controls, but the ratio of the intimal thickness of facial and radial arteries was similar in face transplant recipients compared with controls (1.00 versus 0.95; p = 0.742). Intraobserver correlation showed reliable reproducibility of the measurements (r = 0.935, p ≤ 0.001). Interobserver correlation demonstrated reproducibility of intima measurements (r = 0.422, p ≤ 0.001). CONCLUSION The authors demonstrate that ultrasound biomicroscopy is feasible for postsurgical monitoring, and have developed a new benchmark parameter, the facial artery-to-radial artery intimal thickness ratio, to be used in future testing in the setting of chronic rejection. CLINICAL QUESTION/LEVEL OF EVIDENCE Diagnostic, IV.
Collapse
|
|
38
|
Bedanova H, Orban M, Tretina M, Fila P, Horvath V, Krejci J, Nemec P. Monitoring of allograft vasculopathy by intravascular ultrasound one month and one year after heart transplantation: A single center study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016. [DOI: 10.5507/bp.2015.034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
|
|
39
|
Abstract
The prevalence of heart failure continues to rise due to the aging population and longer survival of people with conditions that lead to heart failure, eg, hypertension, diabetes, and coronary artery disease. Although medical therapy has had an important impact on survival of patients and improving quality of life, heart transplantation remains the definitive therapy for patients that eventually deteriorate. Since the first successful heart transplantation in 1967, significant improvements have been made regarding donor and recipient selection, surgical techniques, and postoperative care. However, the number of potential organ donors has not changed and the growing number of patients in need for transplantation has resulted an increase in waiting list time, and the need for mechanical support. To overcome this issue, the United Network for Organ Sharing implemented an allocation system to prioritize the sickest patients on the list to receive organs. Despite the careful selection of patients, pretransplant immunological screening, and multidrug immunosuppressive regimens, acute and chronic rejections occur and potentially limit graft and patient survival. Treatment for rejection largely depends on the type of rejection, the presence of hemodynamic compromise, and time after transplantation. The limiting factor for long-term graft survival is allograft vasculopathy, an immune-mediated process causing diffuse narrowing of the coronary arteries. Percutaneous coronary intervention and coronary artery bypass surgery are often not an option for this vasculopathy due to the lack of focal lesions, and retransplantation is the only option in appropriate patients.
Collapse
|
|
40
|
Alfonso F, De la Torre Hernández JM. Vasa vasorumand coronary artery disease progression: optical coherence tomography findings. Eur Heart J Cardiovasc Imaging 2016; 17:280-2. [DOI: 10.1093/ehjci/jev318] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
|
|
41
|
Watanabe T, Seguchi O, Nishimura K, Fujita T, Murata Y, Yanase M, Sato T, Sunami H, Nakajima S, Hisamatsu E, Sato T, Kuroda K, Hieda M, Wada K, Hata H, Ishibashi-Ueda H, Miyamoto Y, Fukushima N, Kobayashi J, Nakatani T. Suppressive effects of conversion from mycophenolate mofetil to everolimus for the development of cardiac allograft vasculopathy in maintenance of heart transplant recipients. Int J Cardiol 2016; 203:307-14. [DOI: 10.1016/j.ijcard.2015.10.082] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 09/26/2015] [Accepted: 10/12/2015] [Indexed: 01/08/2023]
|
|
42
|
Tomai F, De Luca L, Petrolini A, Di Vito L, Ghini AS, Corvo P, De Persio G, Parisi F, Pongiglione G, Giulia Gagliardi M, Prati F. Optical coherence tomography for characterization of cardiac allograft vasculopathy in late survivors of pediatric heart transplantation. J Heart Lung Transplant 2016; 35:74-79. [DOI: 10.1016/j.healun.2015.08.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2015] [Revised: 07/14/2015] [Accepted: 08/27/2015] [Indexed: 01/25/2023] Open
|
|
43
|
Park KH, Kwon TG, Matsuzawa Y, Sun T, Liu Z, Lennon RJ, Lerman LO, Kushwaha SS, Lerman A. Association between the vasa vasorum and the atherosclerotic changes in cardiac allograft vasculopathy: volumetric analysis. Eur Heart J Cardiovasc Imaging 2015; 17:272-9. [PMID: 26657475 DOI: 10.1093/ehjci/jev285] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 10/04/2015] [Indexed: 12/14/2022] Open
Abstract
AIMS The current study was designed to test that vasa vasorum (VV) plays a role in the progression of cardiac allograft vasculopathy (CAV) in patients with heart transplantation (HTX). METHODS AND RESULTS Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed in the left anterior descending artery in 19 segments of 19 HTX patients (median 2.1 years from HTX). Each segment is composed of both the continuous lesions: (i) CAV area: intimal thickness >0.5 mm with 5 mm length and (ii) VV area: intimal thickness ≤0.5 mm with 5 mm length. The per cent VV volume (VV volume/vessel volume × 100, %VV) was evaluated in the VV area with OCT (in CAV area VV cannot be assessed because of limited penetration power of OCT). A year later, the association between the baseline %VV and the change in per cent plaque volume (plaque volume/vessel volume × 100, %PV) was evaluated with IVUS. To a normal distribution, Δ%PV (follow-up %PV-initial %PV) was undergone square root transformation. The correlations between the %VV at baseline study and square root-Δ%PV were significant both in the CAV area and in the VV area (r = 0.787, P < 0.001 and r = 0.701, P < 0.001, respectively). In multivariable analysis, only the %VV was significantly correlated with square root-Δ%PV in both areas. CONCLUSION The current study demonstrated a significant association between the VV volume and the progression of plaque volume in both the CAV area and the VV area. Thus, VV may be a potential predictor and possible therapeutic target to attenuate CAV.
Collapse
Affiliation(s)
- Kyoung-Ha Park
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA Division of Cardiovascular Disease, Hallym University Medical Center, Anyang, Korea
| | - Taek-Geun Kwon
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Yasushi Matsuzawa
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Tao Sun
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Zhi Liu
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Ryan J Lennon
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Lilach O Lerman
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Sudhir S Kushwaha
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| | - Amir Lerman
- Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA
| |
Collapse
|
|
44
|
Kueckelhaus M, Fischer S, Seyda M, Bueno EM, Aycart MA, Alhefzi M, ElKhal A, Pomahac B, Tullius SG. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl Int 2015; 29:655-62. [PMID: 26265179 DOI: 10.1111/tri.12652] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/10/2015] [Accepted: 07/30/2015] [Indexed: 12/18/2022]
Abstract
The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes.
Collapse
Affiliation(s)
- Maximilian Kueckelhaus
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany
| | - Sebastian Fischer
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.,Department of Plastic Surgery, BG University Hospital Ludwigshafen, Heidelberg University, Ludwigshafen, Germany
| | - Midas Seyda
- Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Ericka M Bueno
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Mario A Aycart
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Muayyad Alhefzi
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Abdallah ElKhal
- Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Bohdan Pomahac
- Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Stefan G Tullius
- Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
45
|
Goto K, Iakovou I, Gkouziouta A, Maehara A, Mintz GS, Karavolias G, Leontiadis V, Voudris V, Pavlides G, Adamopoulos S. Intravascular Ultrasonic Imaging of Coronary Arterial Remodeling in Heart Transplant Recipients. Am J Cardiol 2015; 116:785-90. [PMID: 26100587 DOI: 10.1016/j.amjcard.2015.05.051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 05/20/2015] [Accepted: 05/20/2015] [Indexed: 11/30/2022]
Abstract
The purpose of this study was to evaluate long-term changes of transplant coronary arteries, including vessel, plaque, and lumen areas. There are limited long-term data on vessel remodeling after heart transplantation. We analyzed serial intravascular ultrasound images of the left anterior descending coronary artery (LAD) in 54 heart transplantation recipients. Nine patients (16.7%) had a history of rejection. Proximal left anterior descending artery segments were matched among time points, a ≥20-mm long segment was analyzed every 1 mm, and results were normalized for analysis length and reported as mm(3)/mm. During follow-up, vessel area decreased (-0.48 ± 1.3 mm(3)/mm/year), and plaque area did not change (-0.01 ± 0.47 mm(3)/mm/year). As a result, lumen area decreased (-0.52 ± 1.34 mm(3)/mm/year). The change in mean lumen area was well correlated to the change in mean vessel area (r = 0.94, p <0.01) but not to the change in mean plaque area (r = -0.27, p = 0.05). In conclusion, lumen loss occurred during long-term follow-up of patients who underwent heart transplantation, primarily secondary to negative remodeling (decrease in vessel dimensions).
Collapse
Affiliation(s)
- Kosaku Goto
- Cardiovascular Research Foundation, New York, New York; Columbia University Medical Center, New York, New York
| | | | | | - Akiko Maehara
- Cardiovascular Research Foundation, New York, New York; Columbia University Medical Center, New York, New York.
| | - Gary S Mintz
- Cardiovascular Research Foundation, New York, New York
| | | | | | | | | | | |
Collapse
|
|
46
|
Badano LP, Miglioranza MH, Edvardsen T, Colafranceschi AS, Muraru D, Bacal F, Nieman K, Zoppellaro G, Marcondes Braga FG, Binder T, Habib G, Lancellotti P, Sicari R, Cosyns B, Donal E, Lombardi M, Sarvari S. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. ACTA ACUST UNITED AC 2015; 16:919-48. [DOI: 10.1093/ehjci/jev139] [Citation(s) in RCA: 141] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 05/02/2015] [Indexed: 01/10/2023]
Affiliation(s)
- Luigi P. Badano
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy
| | | | - Thor Edvardsen
- Department of Cardiology, Oslo University Hospital and University of Oslo, Oslo, Norway
| | | | - Denisa Muraru
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy
| | - Fernando Bacal
- Heart Transplant Department, Heart Institute, University of São Paulo, São Paulo, Brazil
| | - Koen Nieman
- Intensive Cardiac Care Unit and Cardiac CT Research, Erasmus MC, Rotterdam, The Netherlands
| | - Giacomo Zoppellaro
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy
| | | | - Thomas Binder
- Department of Cardiology, University of Vienna, Wien, Austria
| | - Gilbert Habib
- Service de Cardiologie, Hôpital La Timone, Marseille, France
| | - Patrizio Lancellotti
- Department of Cardiology, Heart Valve Clinic, University of Liège, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Wang R, Moura LAZ, Lopes SV, Costa FDAD, Souza Filho NFS, Fernandes TL, Salvatti NB, Faria-Neto JR. Reduced progression of cardiac allograft vasculopathy with routine use of induction therapy with basiliximab. Arq Bras Cardiol 2015; 105:176-83. [PMID: 26107815 PMCID: PMC4559127 DOI: 10.5935/abc.20150063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background Cardiac allograft vasculopathy (CAV) is a major limitation for long-term survival
of patients undergoing heart transplantation (HT). Some immunosuppressants can
reduce the risk of CAV. Objectives The primary objective was to evaluate the variation in the volumetric growth of
the intimal layer measured by intracoronary ultrasound (IVUS) after 1 year in
patients who received basiliximab compared with that in a control group. Methods Thirteen patients treated at a single center between 2007 and 2009 were analyzed
retrospectively. Evaluations were performed with IVUS, measuring the volume of a
coronary segment within the first 30 days and 1 year after HT. Vasculopathy was
characterized by the volume of the intima of the vessel. Results Thirteen patients included (7 in the basiliximab group and 6 in the control
group). On IVUS assessment, the control group was found to have greater vessel
volume (120–185.43 mm3 vs. 127.77–131.32 mm3; p = 0.051). Intimal layer
growth (i.e., CAV) was also higher in the control group (27.30–49.15
mm3 [∆80%] vs. 20.23–26.69 mm3 [∆33%]; p = 0.015).
Univariate regression analysis revealed that plaque volume and prior
atherosclerosis of the donor were not related to intima growth (r = 0.15, p =
0.96), whereas positive remodeling was directly proportional to the volumetric
growth of the intima (r = 0.85, p < 0.001). Conclusion Routine induction therapy with basiliximab was associated with reduced growth of
the intima of the vessel during the first year after HT.
Collapse
|
|
48
|
Enns W, von Rossum A, Choy J. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis. J Vis Exp 2015:e52800. [PMID: 26066300 DOI: 10.3791/52800] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA.
Collapse
Affiliation(s)
- Winnie Enns
- Department of Molecular Biology and Biochemistry, Simon Fraser University
| | - Anna von Rossum
- Department of Molecular Biology and Biochemistry, Simon Fraser University
| | - Jonathan Choy
- Department of Molecular Biology and Biochemistry, Simon Fraser University;
| |
Collapse
|
|
49
|
Ichibori Y, Ohtani T, Nakatani D, Tachibana K, Yamaguchi O, Toda K, Akasaka T, Fukushima N, Sawa Y, Komuro I, Kotani JI, Sakata Y. Optical coherence tomography and intravascular ultrasound evaluation of cardiac allograft vasculopathy with and without intimal neovascularization. Eur Heart J Cardiovasc Imaging 2015; 17:51-8. [PMID: 25976347 DOI: 10.1093/ehjci/jev110] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 04/08/2015] [Indexed: 11/14/2022] Open
Abstract
AIMS Neovascularization is closely associated with plaque progression in non-heart transplantation subjects; on the other hand, cardiac allograft vasculopathy causes unfavourable outcomes. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can provide microscopic assessment in vivo. The aim of this study was to investigate the impact of neovascularization on intimal proliferation. METHODS AND RESULTS Both IVUS and OCT were attempted in 45 consecutive patients during annual catheterization after heart transplantation. There were 115 vessels [28 vessels were catheterized within 8 weeks of heart transplantation (baseline)]. IVUS analysis assessed vessel, luminal, and intimal (vessel-lumen) volume using Simpson's method. Qualitative parameters including microchannel were assessed by OCT. A microchannel was defined as a no-signal tubuloluminal structure with a sharply delineated border considered to represent neovascularization. Microchannel was observed more often in patient who had their heart transplant more than a year prior to the imaging, compared with shorter periods (39.1 vs. 10.7%, P = 0.023). All microchannels were seen in thickness >0.5 mm, and intimal volume index (mm(3)/mm) correlated with frequency of microchannel (r = 0.54, P = 0.04). The risks for microchannels were donor age [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.22; P = 0.007], cytomegalovirus infection (OR 16.21; 95% CI 1.79-220.09; P = 0.012), diabetes (OR 9.5; 95% CI 1.21-116.10; P = 0.032), LDL-cholesterol (OR 1.07; 95% CI 1.01-1.13; P = 0.010), and intimal volume (OR 2.47; 95% CI 1.13-6.36; P = 0.023). CONCLUSION OCT-identified microchannels increased sharply within the first year and were correlated with intimal volume and coronary risks. This suggests that neovascularization may play an important role in the progression of cardiac allograft vasculopathy.
Collapse
Affiliation(s)
- Yasuhiro Ichibori
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Tomohito Ohtani
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Daisaku Nakatani
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Kouichi Tachibana
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Osamu Yamaguchi
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Koichi Toda
- Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takashi Akasaka
- Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan
| | - Norihide Fukushima
- Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoshiki Sawa
- Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Issei Komuro
- Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Jun-ichi Kotani
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| | - Yasushi Sakata
- Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
| |
Collapse
|
|
50
|
Skorić B, Čikeš M, Ljubas Maček J, Baričević Ž, Škorak I, Gašparović H, Biočina B, Miličić D. Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis. Croat Med J 2015; 55:562-76. [PMID: 25559827 PMCID: PMC4295072 DOI: 10.3325/cmj.2014.55.562] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.
Collapse
Affiliation(s)
- Boško Skorić
- Bosko Skoric, University of Zagreb School of Medicine, Department of Cardiovascular Diseases, University Hospital Center Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia,
| | | | | | | | | | | | | | | |
Collapse
|