Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.09.020
Nowell M. Fine MD, SM
{"title":"Performing Heart Transplants for Adult Congenital Heart Disease Patients at High Volume Centres","authors":"Nowell M. Fine MD, SM","doi":"10.1016/j.cjca.2025.09.020","DOIUrl":"10.1016/j.cjca.2025.09.020","url":null,"abstract":"","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 403-405"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.11.012
Ilan Richter MD, MPH , Jayant Raikhelkar MD , Kevin Clerkin MD , Ersilia M. DeFilippis MD , Deborah Estrin PhD , Dor Lotan MD , Boaz Elad MD , Gabriel Sayer MD , Nir Uriel MD, MSc
The advent of AI in medicine has allowed for transformative advances across clinical domains. In the field of heart transplantation, existing paradigms for patient identification, transplant outcomes optimization, post-transplant surveillance, and more are amenable to improved performance by machine learning and other models. Studies published thus far have largely relied on retrospective designs and focused on clinical outcomes; nevertheless, emerging evidence is tackling organ allocation considerations, optimal donor-recipient matching schemes, predictors of primary graft dysfunction, and reduced survival. In this review we survey current and future applications of AI in heart transplantation, and identify focus areas for clinicians and researchers.
{"title":"Novel Artificial Intelligence Applications in Heart Transplantation","authors":"Ilan Richter MD, MPH , Jayant Raikhelkar MD , Kevin Clerkin MD , Ersilia M. DeFilippis MD , Deborah Estrin PhD , Dor Lotan MD , Boaz Elad MD , Gabriel Sayer MD , Nir Uriel MD, MSc","doi":"10.1016/j.cjca.2025.11.012","DOIUrl":"10.1016/j.cjca.2025.11.012","url":null,"abstract":"<div><div>The advent of AI in medicine has allowed for transformative advances across clinical domains. In the field of heart transplantation, existing paradigms for patient identification, transplant outcomes optimization, post-transplant surveillance, and more are amenable to improved performance by machine learning and other models. Studies published thus far have largely relied on retrospective designs and focused on clinical outcomes; nevertheless, emerging evidence is tackling organ allocation considerations, optimal donor-recipient matching schemes, predictors of primary graft dysfunction, and reduced survival. In this review we survey current and future applications of AI in heart transplantation, and identify focus areas for clinicians and researchers.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 255-264"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.11.050
Parham Hassanzadeh BSc , Adrien Lam BSc , Mitchell J. Wagner MSc , Jennifer Conway MD, MSc , Darren H. Freed MD, PhD
Heart transplantation remains the gold standard for end-stage heart failure, yet access is limited by geography, organ shortages, and preservation technology. In Canada, long wait times and organ underutilization persist due to the use of static cold storage (SCS), the current standard. Although SCS is cost-effective and technically simple, its short ischemic window and the inability to monitor heart function restrict donor heart viability. This review examines the evolution of preservation methods, with a focus on SCS and novel machine perfusion systems that aim to address the limitations of SCS. Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) both provide extended preservation times and metabolic support. HMP delivers cold, oxygenated or non-oxygenated perfusate to minimize ischemia, while NMP maintains the donor heart at body temperature in a semi-physiological state, allowing for functional monitoring and therapeutic reconditioning. Various technologies have already demonstrated success in large animal models and select clinical trials, with promising results for extended preservation intervals and DCC heart use. Normothermic regional perfusion (NRP) is a method for initial resuscitation of the DCC heart, by restoring circulation in situ before procurement and reducing ischemic injury. Its adoption in Europe and the United States (U.S.) has accelerated DCC heart donation while maintaining excellent outcomes. With new ethical guidelines supporting Canada’s use, pilot programs are now possible. To improve transplant equity and maximize heart utilization, Canada can invest in machine perfusion research, infrastructure, and national implementation strategies. These technologies offer not only extended viability but also decrease waitlist mortality.
{"title":"Advancements in Donor Heart Preservation Methods: A Review of Approaches","authors":"Parham Hassanzadeh BSc , Adrien Lam BSc , Mitchell J. Wagner MSc , Jennifer Conway MD, MSc , Darren H. Freed MD, PhD","doi":"10.1016/j.cjca.2025.11.050","DOIUrl":"10.1016/j.cjca.2025.11.050","url":null,"abstract":"<div><div>Heart transplantation remains the gold standard for end-stage heart failure, yet access is limited by geography, organ shortages, and preservation technology. In Canada, long wait times and organ underutilization persist due to the use of static cold storage (SCS), the current standard. Although SCS is cost-effective and technically simple, its short ischemic window and the inability to monitor heart function restrict donor heart viability. This review examines the evolution of preservation methods, with a focus on SCS and novel machine perfusion systems that aim to address the limitations of SCS. Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) both provide extended preservation times and metabolic support. HMP delivers cold, oxygenated or non-oxygenated perfusate to minimize ischemia, while NMP maintains the donor heart at body temperature in a semi-physiological state, allowing for functional monitoring and therapeutic reconditioning. Various technologies have already demonstrated success in large animal models and select clinical trials, with promising results for extended preservation intervals and DCC heart use. Normothermic regional perfusion (NRP) is a method for initial resuscitation of the DCC heart, by restoring circulation in situ before procurement and reducing ischemic injury. Its adoption in Europe and the United States (U.S.) has accelerated DCC heart donation while maintaining excellent outcomes. With new ethical guidelines supporting Canada’s use, pilot programs are now possible. To improve transplant equity and maximize heart utilization, Canada can invest in machine perfusion research, infrastructure, and national implementation strategies. These technologies offer not only extended viability but also decrease waitlist mortality.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 297-309"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.05.023
Xiaoxue Zhang MS , Huan Wang MS , Yujie Yang MS , Xiantao Ma MD , Yi Feng MS , Chenxi Yan MS , Min Hu MD, PhD , Shiliang Li MD, PhD , Cai Cheng MD, PhD
Heart transplantation has traditionally relied on donation after brain death (DBD), but persistent shortages in available donor hearts have elevated interest in donation after circulatory death (DCD). Despite DCD now composing a significant share of organ donations globally, clinical implementation remains challenged by limited evidence, procedural inconsistencies, and higher risks of ischemia injury and primary graft dysfunction. Recent technologic advancements in organ prefusion, particularly normothermic regional perfusion (NRP) and ex situ machine perfusion techniques, have demonstrated improved outcomes for DCD transplants, with short- and mid-term survival rates comparable to DBD. Clinical evidence suggests that effective management of warm ischemia and optimised donor selection criteria can mitigate risks, achieving high utilisation rates and excellent recipient outcomes. Nonetheless, significant global variations in DCD practices indicate the need for standardised guidelines to improve adoption rates and consistency in results. Future directions include refining perfusion technologies, clarifying thresholds for ischemia times, identifying real-time biomarkers for graft viability, and expanding large-scale comparative studies to conclusively evaluate long-term outcomes. With these challenges addressed through structured protocols and ongoing technologic innovations, DCD heart transplantation holds substantial potential to significantly broaden the donor pool and improve survival outcomes, representing a pivotal advance in addressing global shortages of transplantable hearts.
{"title":"Donation After Circulatory Death in Heart Transplantation","authors":"Xiaoxue Zhang MS , Huan Wang MS , Yujie Yang MS , Xiantao Ma MD , Yi Feng MS , Chenxi Yan MS , Min Hu MD, PhD , Shiliang Li MD, PhD , Cai Cheng MD, PhD","doi":"10.1016/j.cjca.2025.05.023","DOIUrl":"10.1016/j.cjca.2025.05.023","url":null,"abstract":"<div><div><span><span>Heart transplantation has traditionally relied on donation after brain death (DBD), but persistent shortages in available donor hearts have elevated interest in donation after circulatory death (DCD). Despite DCD now composing a significant share of organ donations globally, clinical implementation remains challenged by limited evidence, procedural inconsistencies, and higher risks of </span>ischemia<span> injury and primary graft dysfunction<span>. Recent technologic advancements in organ prefusion, particularly normothermic regional perfusion (NRP) and </span></span></span><em>ex situ</em><span> machine perfusion techniques, have demonstrated improved outcomes for DCD transplants, with short- and mid-term survival rates comparable to DBD. Clinical evidence suggests that effective management of warm ischemia and optimised donor selection criteria can mitigate risks, achieving high utilisation rates and excellent recipient outcomes. Nonetheless, significant global variations in DCD practices indicate the need for standardised guidelines to improve adoption rates and consistency in results. Future directions include refining perfusion technologies, clarifying thresholds for ischemia times, identifying real-time biomarkers for graft viability, and expanding large-scale comparative studies to conclusively evaluate long-term outcomes. With these challenges addressed through structured protocols and ongoing technologic innovations, DCD heart transplantation holds substantial potential to significantly broaden the donor pool and improve survival outcomes, representing a pivotal advance in addressing global shortages of transplantable hearts.</span></div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 265-285"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.09.021
Simon Keith CM
{"title":"Forty Years With a Transplanted Heart: A Life of Resilience, Gratitude, and Relentless Purpose","authors":"Simon Keith CM","doi":"10.1016/j.cjca.2025.09.021","DOIUrl":"10.1016/j.cjca.2025.09.021","url":null,"abstract":"","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 414-416"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.11.024
Ashish H. Shah MD, MD-Research , Darren H. Freed MD, PhD , Anantharaman Rajaram MD , Oscar Fernandez MD , Richard A. Krasuski MD , Katrijn Jansen MD
With advances in congenital heart disease (CHD) management, most infants now survive into adulthood. Heart failure (HF) remains the leading cause of death in this growing adult cohort. CHD patients can present with unique characteristics of failure, not only making diagnosis more challenging but also limiting the response to guideline-directed HF strategies. Heart transplantation in those with end-stage failure remains the final treatment option. Distinct from the acquired HF population, CHD patients often present with complex anatomical and physiological features, and comprehensive multidisciplinary evaluation of potential transplant candidates in an expert adult CHD transplant centre is recommended. This review summarizes the current understanding of heart transplantation in CHD patients, with a focus on historical perspective and improved outcomes, surgical considerations, immunological challenges, organ allocation policies, and special considerations in the Fontan population, including the emerging role of combined heart-liver transplantation.
{"title":"Challenges and Growing experience in Heart Transplantation in Adult Congenital Heart Disease","authors":"Ashish H. Shah MD, MD-Research , Darren H. Freed MD, PhD , Anantharaman Rajaram MD , Oscar Fernandez MD , Richard A. Krasuski MD , Katrijn Jansen MD","doi":"10.1016/j.cjca.2025.11.024","DOIUrl":"10.1016/j.cjca.2025.11.024","url":null,"abstract":"<div><div>With advances in congenital heart disease (CHD) management, most infants now survive into adulthood. Heart failure (HF) remains the leading cause of death in this growing adult cohort. CHD patients can present with unique characteristics of failure, not only making diagnosis more challenging but also limiting the response to guideline-directed HF strategies. Heart transplantation in those with end-stage failure remains the final treatment option. Distinct from the acquired HF population, CHD patients often present with complex anatomical and physiological features, and comprehensive multidisciplinary evaluation of potential transplant candidates in an expert adult CHD transplant centre is recommended. This review summarizes the current understanding of heart transplantation in CHD patients, with a focus on historical perspective and improved outcomes, surgical considerations, immunological challenges, organ allocation policies, and special considerations in the Fontan population, including the emerging role of combined heart-liver transplantation.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 381-393"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.11.014
Feras Alkhalaileh MD, Gustavo Duarte MD, David A. Baran MD
Heart transplantation remains the definitive therapy for end stage heart failure, delivering survival and quality-of-life benefits unmatched by alternative strategies. Contemporary outcomes are excellent, with one year survival now exceeding 90% in the United States, reflecting advances in surgical practice, donor management, and perioperative care. However, despite these gains, long-term survival remains largely unchanged, with most attrition beyond the first year still driven by coronary allograft vasculopathy, malignancy, renal failure, infection, and the cumulative toxicity of chronic immunosuppression.This review synthesizes registry data, clinical trial evidence, and long-term cohort studies to define the barriers that prevent recipients from thriving beyond the first decade of transplant. It examines the rising burden of cancer, alongside the dual immunologic and atherosclerotic pathways of coronary allograft vasculopathy. It also evaluates the effects of adherence to immunosuppression and impact of diabetes, hypertension, and chronic kidney disease, and appraises evidence-based surveillance and treatment strategies to improve long-term outcomes. Long-term survival analyses, including the fifteen-year follow-up of the TICTAC trial and studies of “thrivers,” show that steroid sparing strategies and careful early management can yield survival well beyond twenty years.Maximizing the gift of transplantation requires precision immunosuppression guided by emerging molecular tools, comprehensive cancer and cardiovascular prevention, structured adherence programs, and health systems that extend early excellence across the lifespan. With such strategies, the goal shifts from merely prolonging life to enabling heart transplantation recipients to live longer, healthier, and more complete lives.
{"title":"Thriving Long Term After Heart Transplantation","authors":"Feras Alkhalaileh MD, Gustavo Duarte MD, David A. Baran MD","doi":"10.1016/j.cjca.2025.11.014","DOIUrl":"10.1016/j.cjca.2025.11.014","url":null,"abstract":"<div><div>Heart transplantation remains the definitive therapy for end stage heart failure, delivering survival and quality-of-life benefits unmatched by alternative strategies. Contemporary outcomes are excellent, with one year survival now exceeding 90% in the United States, reflecting advances in surgical practice, donor management, and perioperative care. However, despite these gains, long-term survival remains largely unchanged, with most attrition beyond the first year still driven by coronary allograft vasculopathy, malignancy, renal failure, infection, and the cumulative toxicity of chronic immunosuppression.This review synthesizes registry data, clinical trial evidence, and long-term cohort studies to define the barriers that prevent recipients from thriving beyond the first decade of transplant. It examines the rising burden of cancer, alongside the dual immunologic and atherosclerotic pathways of coronary allograft vasculopathy. It also evaluates the effects of adherence to immunosuppression and impact of diabetes, hypertension, and chronic kidney disease, and appraises evidence-based surveillance and treatment strategies to improve long-term outcomes. Long-term survival analyses, including the fifteen-year follow-up of the TICTAC trial and studies of “thrivers,” show that steroid sparing strategies and careful early management can yield survival well beyond twenty years.Maximizing the gift of transplantation requires precision immunosuppression guided by emerging molecular tools, comprehensive cancer and cardiovascular prevention, structured adherence programs, and health systems that extend early excellence across the lifespan. With such strategies, the goal shifts from merely prolonging life to enabling heart transplantation recipients to live longer, healthier, and more complete lives.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 406-413"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite major advances in short-term outcomes after heart transplantation, long-term survival remains limited by chronic allograft dysfunction, with cardiac allograft vasculopathy (CAV) being the leading cause of late graft failure and an important cause of all-cause mortality. CAV is a unique and multifactorial form of transplant coronary vasculopathy, driven by a complex interplay of alloimmune responses, innate immune activation, and traditional cardiovascular risk factors. Recent insights from deep profiling of human allograft tissue have revealed the key roles of locally sustained T- and B-cell–mediated inflammation, macrophage–natural killer cell interactions, and chronic immune activation within the graft. These discoveries challenge earlier models of systemic immune monitoring and highlight the importance of spatially organised intragraft immune processes. In parallel, the diagnostic landscape of CAV is rapidly evolving. High-resolution imaging techniques, such as optical coherence tomography, and advanced noninvasive tools, including coronary computed tomography angiography and positron emission tomography, not only enable earlier and more precise detection of disease, but also redefine the usual landscape of CAV diagnosis. New methods for individualised risk stratification, including trajectory modelling and machine learning–enhanced biopsy analysis, are paving the way for more personalised surveillance strategies. While current management remains focused on prevention, novel therapeutic targets are emerging, informed by a deeper understanding of CAV immunopathogenesis. This review provides an up-to-date synthesis of recent advances in CAV, with a focus on pathophysiology, individualised risk assessment, diagnostic innovation, and therapeutic perspectives, underscoring a paradigm shift toward more precise and proactive care in heart transplant recipients.
{"title":"New Insights Into Pathogenesis, Diagnosis, and Management of Cardiac Allograft Vasculopathy","authors":"Pauline David MD , Pilar Roquero MD , Guillaume Coutance MD, PhD","doi":"10.1016/j.cjca.2025.09.040","DOIUrl":"10.1016/j.cjca.2025.09.040","url":null,"abstract":"<div><div>Despite major advances in short-term outcomes after heart transplantation, long-term survival remains limited by chronic allograft dysfunction, with cardiac allograft vasculopathy (CAV) being the leading cause of late graft failure and an important cause of all-cause mortality. CAV is a unique and multifactorial form of transplant coronary vasculopathy, driven by a complex interplay of alloimmune responses, innate immune activation, and traditional cardiovascular risk factors. Recent insights from deep profiling of human allograft tissue have revealed the key roles of locally sustained T- and B-cell–mediated inflammation, macrophage–natural killer cell interactions, and chronic immune activation within the graft. These discoveries challenge earlier models of systemic immune monitoring and highlight the importance of spatially organised intragraft immune processes. In parallel, the diagnostic landscape of CAV is rapidly evolving. High-resolution imaging techniques, such as optical coherence tomography, and advanced noninvasive tools, including coronary computed tomography angiography and positron emission tomography, not only enable earlier and more precise detection of disease, but also redefine the usual landscape of CAV diagnosis. New methods for individualised risk stratification, including trajectory modelling and machine learning–enhanced biopsy analysis, are paving the way for more personalised surveillance strategies. While current management remains focused on prevention, novel therapeutic targets are emerging, informed by a deeper understanding of CAV immunopathogenesis. This review provides an up-to-date synthesis of recent advances in CAV, with a focus on pathophysiology, individualised risk assessment, diagnostic innovation, and therapeutic perspectives, underscoring a paradigm shift toward more precise and proactive care in heart transplant recipients.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 335-345"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.10.005
Erik Henricksen PharmD , Krysta Walter PharmD , Alicia Lichvar PharmD, MS
Antibody-mediated rejection (AMR) continues to be a significant and challenging complication after alternative surgical methods, contributing significantly to morbidity and mortality. Despite its clear clinical impact, there is no consensus on optimal treatment strategies due to a paucity of prospective clinical trials and the immunologic nuances of this rejection phenotype. Therapeutic plasma exchange and intravenous immunoglobulin remain the cornerstones of most AMR protocols. However, there is growing evidence supporting the use of additional therapies that target more specific antibody mechanisms. Anti-CD20 antibodies, proteasome inhibitors, anti-CD38 antibodies, interleukin-6 receptor antagonists, and complement inhibitors have been used to reverse AMR and mitigate its deleterious consequences. However, these medications come with their own nuances and considerations for use. Therefore, the purpose of this review was to provide practical “how-to” information on the use of these agents, including prescribing, dosing strategies, monitoring approaches, and duration of treatment. In addition, a key focus was placed on adverse effects profiles associated with AMR treatment with these novel agents through monitoring and risk mitigation approaches to ensure patient safety. In this way, our review aims to serve as a comprehensive and practical guide for clinicians, synthesizing existing data on both standard and emerging AMR therapies to improve patient outcomes after heart transplantation.
{"title":"Current State of Drug Therapies for Antibody-mediated Rejection After Heart Transplantation","authors":"Erik Henricksen PharmD , Krysta Walter PharmD , Alicia Lichvar PharmD, MS","doi":"10.1016/j.cjca.2025.10.005","DOIUrl":"10.1016/j.cjca.2025.10.005","url":null,"abstract":"<div><div>Antibody-mediated rejection (AMR) continues to be a significant and challenging complication after alternative surgical methods, contributing significantly to morbidity and mortality. Despite its clear clinical impact, there is no consensus on optimal treatment strategies due to a paucity of prospective clinical trials and the immunologic nuances of this rejection phenotype. Therapeutic plasma exchange and intravenous immunoglobulin remain the cornerstones of most AMR protocols. However, there is growing evidence supporting the use of additional therapies that target more specific antibody mechanisms. Anti-CD20 antibodies, proteasome inhibitors, anti-CD38 antibodies, interleukin-6 receptor antagonists, and complement inhibitors have been used to reverse AMR and mitigate its deleterious consequences. However, these medications come with their own nuances and considerations for use. Therefore, the purpose of this review was to provide practical “how-to” information on the use of these agents, including prescribing, dosing strategies, monitoring approaches, and duration of treatment. In addition, a key focus was placed on adverse effects profiles associated with AMR treatment with these novel agents through monitoring and risk mitigation approaches to ensure patient safety. In this way, our review aims to serve as a comprehensive and practical guide for clinicians, synthesizing existing data on both standard and emerging AMR therapies to improve patient outcomes after heart transplantation.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 346-355"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.cjca.2025.11.008
Lauren K. Truby MD, MS, FACC , Gaurav Sharma PhD , William D. Watson BSc(Hons), DPhil, MBBChir , Philip F. Halloran MD, PhD , Tafsia Hussain MSc , Katelynn S. Madill-Thomsen PhD , Gabriel Esmailian MD , Nicole Fung BSc , Eliot Peyster MD, MS , Yasbanoo Moayedi MD , Vivek Rao MD, PhD , Darren Freed MD, PhD , Dawn E. Bowles PhD , Matthias Peltz MD , Filio Billia MD, PhD, FACC
Heart transplantation remains the gold standard treatment for end-stage heart failure. Yet, challenges such as ischemia-reperfusion injury, primary graft dysfunction, allograft rejection, and cardiac allograft vasculopathy continue to affect long-term patient outcomes. In this contemporary review, we explore the applications of basic science in enhancing heart transplantation practices. We describe the molecular mechanisms of ischemic-reperfusion injuty, emphasizing the role of reactive oxygen species and mitochondrial dysfunction, which contribute to graft viability and post-transplant dysfunction. We also examine the evolution of preservation strategies, highlighting advancements from static cold storage to dynamic machine perfusion techniques, including hypothermic and normothermic systems that provide metabolic support and improve graft function. The potential of emerging biomarkers, such as circulating cell-free DNA and innovative diagnostic tools like the Molecular Microscope Diagnostic System, are discussed as vital tools for monitoring graft health and predicting rejection. By leveraging these advancements, the field of heart transplantation can address current challenges, improve patient outcomes, and enhance quality of life for transplant recipients. The importance of continued collaboration between researchers and clinicians in translating scientific discoveries into effective clinical applications cannot be overstated.
{"title":"From the Bench to the Bedside and Back: Contemporary Applications of Basic Science to Innovations in Heart Transplantation","authors":"Lauren K. Truby MD, MS, FACC , Gaurav Sharma PhD , William D. Watson BSc(Hons), DPhil, MBBChir , Philip F. Halloran MD, PhD , Tafsia Hussain MSc , Katelynn S. Madill-Thomsen PhD , Gabriel Esmailian MD , Nicole Fung BSc , Eliot Peyster MD, MS , Yasbanoo Moayedi MD , Vivek Rao MD, PhD , Darren Freed MD, PhD , Dawn E. Bowles PhD , Matthias Peltz MD , Filio Billia MD, PhD, FACC","doi":"10.1016/j.cjca.2025.11.008","DOIUrl":"10.1016/j.cjca.2025.11.008","url":null,"abstract":"<div><div>Heart transplantation remains the gold standard treatment for end-stage heart failure. Yet, challenges such as ischemia-reperfusion injury, primary graft dysfunction, allograft rejection, and cardiac allograft vasculopathy continue to affect long-term patient outcomes. In this contemporary review, we explore the applications of basic science in enhancing heart transplantation practices. We describe the molecular mechanisms of ischemic-reperfusion injuty, emphasizing the role of reactive oxygen species and mitochondrial dysfunction, which contribute to graft viability and post-transplant dysfunction. We also examine the evolution of preservation strategies, highlighting advancements from static cold storage to dynamic machine perfusion techniques, including hypothermic and normothermic systems that provide metabolic support and improve graft function. The potential of emerging biomarkers, such as circulating cell-free DNA and innovative diagnostic tools like the Molecular Microscope Diagnostic System, are discussed as vital tools for monitoring graft health and predicting rejection. By leveraging these advancements, the field of heart transplantation can address current challenges, improve patient outcomes, and enhance quality of life for transplant recipients. The importance of continued collaboration between researchers and clinicians in translating scientific discoveries into effective clinical applications cannot be overstated.</div></div>","PeriodicalId":9555,"journal":{"name":"Canadian Journal of Cardiology","volume":"42 2","pages":"Pages 233-254"},"PeriodicalIF":5.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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