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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

The International Society for Heart and Lung Transplantation (ISHLT) Guidelines for the Care of Heart Transplant Recipients

Published:December 20, 2022DOI:https://doi.org/10.1016/j.healun.2022.10.015

      ABBREVIATIONS:

      AAIR (atrium paced, atrium sensed inhibited rate modulation), ABOi (ABO incompatible), ACC (American College of Cardiology), ACEI (angiotensin converting enzyme inhibitor), ACR (acute cellular rejection), ACT (activated clotting time), ADA (American Diabetes Association), AHA (American Heart Association), AMR (antibody-mediated rejection), AP (aerosolized pentamidine), aPTT (activated partial thromboplastin time), ARB (angiotensin receptor blocker), ASD (atrial septal defect), ATG (anti-thymocyte globulin), AV (arteriovenous), AZA (azathioprine), BiV (biventricular), BMD (bone mass density), BNP (brain natriuretic peptide), BPAR (proven acute rejection), CAV (cardiac allograft vasculopathy), CBCR (center-based cardiac rehabilitation), CCB (calcium channel blocker), CCTA (Coronary computed tomography angiography), CEDIA (cloned enzyme donor immunoassay method), CHD (congenital heart disease), CI (cardiac index), CKD (chronic kidney disease), CO (cardiac output), CPB (cardiopulmonary bypass), c-PRA (calculated PRA), CMV (cytomegalovirus), CNI (calcineurin inhibitor), CRP (C-reactive protein), CS (corticosteroid), CT (computed tomography), CVP (central venous pressure), CYA (cyclosporine), CYP3A (cytochrome P-450 3A4), DDDR (dual-paced, dual-sensed, dual-response to sensing, rate modulation), DEXA (dual energy x-ray absorptiometry), DSA (donor specific antibody), ECG (electrocardiogram), ED (erectile dysfunction), ECMO (extracorporeal membrane oxygenation), EMB (endomyocardial biopsy), EMIT (enzyme multiplied immunoassay technique), ESC (European Society of Cardiology), EVL (everolimus), FFP (fresh frozen plasma), GEP (Gene Expression Profiling-Allomap), GFR (glomerular filtration rate), HBCR (Home-based cardiac rehabilitation), Hgb (hemoglobin), HIT (heparin-induced thrombocytopenia), HIV (Human Immunosdefiency virus), HLA (human leukocyte antigen), HPLC (high-performance liquid chromatography), HPV (human papillomavirus), HRS (Heart Rhythm Society), HSV (herpes simplex virus), HT (heart transplant), ICU (intensive care unit), Ig (immunoglobulin), IgG (immunoglobulin G), IH (Isohemagglutinin), INR (international normalized unit), IABP (intra-aortic balloon pump), ISHLT (International Society for Heart and Lung Transplantation), IUD (intrauterine device), IV (intravenous), IVUS (intravascular ultrasound), LV (left ventricle), LVAD (left ventricular assist device), LVEF (left ventricular ejection fraction), LVH (left ventricular hypertrophy), MAOI (monoamine oxidase inhibitors), MCS (mechanical circulatory support), MDRD equation (modified diet in renal disease equation), MFI (mean fluorescent intensity), MMF (mycophenolate mofetil), MPA (mycophenolic acid), mTOR (mammalian target of rapamycin), MVO2 (mixed venous oxygen), PAWP (pulmonary artery wedge pressure), PCC (prothrombin plasma concentrates), PFA-100 (platelets function assay 100), PGF (primary graft failure), PRA (panel reactive antibodies), PRES (posterior reversible leukoencephalopathy), PCSK9 (Proprotein convertase subtilisin-kexin type 9), PSI (proliferation signal inhibitor), PTLD (posttransplant lymphoproliferative disorder), PT (prothrombin time), PTT (partial thromboplastin time), PVR (pulmonary vascular resistance), RAP (right atrial pressure), rFVII (recombinant factor 7), RV (right ventricle), sCr (serum creatinine), SPECT (single-photon emission computed tomography), SRL (sirolimus), STI (sexually transmitted infection), SVT (sustained ventricular tachycardia), TAC (tacrolimus), TEE (transesophageal echocardiogram), TMP/SMZ (trimethoprim/sulfamethoxazole), TPG (Trans-Pulmonary Gradient), TTE (transthoracic echocardiogram), TV (tricuspid valve), VAD (ventricular assist device), VER (ventricular evoked responses), VT (ventricular tachycardia)

      Independent Expert Reviewers

      David Baran, Tiffany Buda, Adam Cochrane, Maria Crespo Leiro, Anne Dipchand, Brian Feingold, Kathleen Grady, Edward Horn, Maryl Johnson, Donna Mancini, Sean Pinney, Heather Ross, Kari Wujcik, Andreas Zuckermann
      The International Society for Heart and Lung Transplantion (ISHLT) Guidelines for the Care of Heart Transplant Recipients were originally published in 2010. These guidelines provided the first comprehensive guideline for the care of Heart Transplant patients. A great deal has changed in the years after this initial unprecedented document. The ISHLT has made the commitment to convene experts in all areas of heart transplantation to develop a focused update to the original practice guidelines. Writers and Chairs were charged with reviewing the existing guidelines and where signifigant new literature exists, updating those original recommendations. Additionally, they were charged to add specific new areas of focus that were undeveloped, undiscovered, or unsupported at the time of the original publication. After a vast effort involving 39 writers from 11 countries worldwide, the “ISHLT Guidelines for the Care of Heart Transplant Recipients” has now been completed and the Executive Summary of these guidelines is the subject of this article.
      The document results from the work of 4 Task Force groups each co-chaired by a pediatric heart transplant clincian who had the specific mandate to highlight issues unique to the pediatric heart transplant population and to ensure their adequate representation.
      • Task Force 1 addresses the peri-operative care of heart transplant recipients, including:
        • Pre-Transplant Optimization
        • Surgical Issues Impacting Care in the Immediate Post-operative Period
        • Considerations in Patients Bridged with Mechanical Circulatory Support
        • Early Post-Operative Care of the Heart Transplant Recipient
        • Evaluation of Allosensitization, Approaches to Sensitized Heart Transplant Recipients, and Hyperacute and Delayed Antibody-Mediated Rejection
        • Management of ABO “Incompatible” Heart Transplant Recipients
        • Coagulopathies in Heart Transplant Surgery
        • Documentation and Communication with the Multidisciplinary Team
        • Use of Extracorporeal Membrane Oxygenation for the Management of Primary Graft
      • Task Force 2 discusses the Immunosuppression and Rejection including:
        • Rejection Surveillance
        • Monitoring of Immunosuppressive Drug Levels
        • Principles of Immunosuppression and Recommended Regimens
        • Treatment of Acute Cellular Rejection
        • Treatment of Hyperacute and Antibody-Mediated Rejection
        • Management of Late Acute Rejection
      • Task Force 3 addresses the Long-term Care of Heart Transplant Recipients; Management of Complications including:
        • Minimization of Immunosuppression
        • Management of Neurologic Complications After Heart Transplantation
        • Cardiac Allograft Vasculopathy
        • Malignancy After Heart Transplantation
        • Chronic Kidney Disease After Heart Transplantation
        • Management of Cardiovascular Risk After Heart Transplantation
        • Other Complications of Chronic Immunosuppression
        • Arrhythmias
        • Anticoagulation after Heart Transplant
        • Monitoring Recipients of Organs from Donors at Higher Risk of Infectious Diseases
        • Graft Failure & Considerations for Cardiac Retransplantation
      • Taskforce 4 covers the Long-term Care of Heart Transplant Recipients: Prevention and Prophylaxis including:
        • Frequency of Routine Tests and Clinic Visits in Heart Transplant Recipients
        • Prophylaxis for Corticosteroid-Induced Bone Disease
        • Exercise, Nutrition and Physical Rehabilitation After Heart Transplantation
        • Management of Intercurrent Surgery in Heart Transplant Recipients
        • Reproductive Health After Heart Transplantation
        • Psychosocial and Psychologic Issues Particularly Related to Adherence to Medical Therapy in Heart Transplant Recipients
        • Substance Use & Abuse
        • Endocarditis Prophylaxis After Heart Transplantation
        • Return to Work or School and Occupational Restrictions After Heart Transplantation
        • Return to Operating a Vehicle After Heart Transplantation
        • Family Screening
        • Management of the Transition from Pediatric to Adult Care After Heart Transplantation
        • Principles of Shared Care After Heart Transplantation
        • Travelling After Heart Transplant
        • Emerging Pathogens, Epidemics and Pandemic Considerations for Heart Transplant Recipients
      International Society for Heart and Lung Transplantation Standards and Guidelines Committee Grading Criteria
      Tabled 1
      Class IEvidence and/or general agreement that a given treatment or procedure is beneficial, useful, and effective
      Class IIConflicting evidence and/or divergence of opinion about the usefulness/efficacy of the treatment or procedure
      Class IIaWeight of evidence/opinion is in favor of usefulness/efficacy
      Class IIbUsefulness/efficacy is less well established by evidence/opinion
      Class IIIEvidence or general agreement that the treatment or procedure is not useful or effective and in some cases may be harmful
      Level of evidence AData derived from multiple randomized clinical trials or meta-analyses
      Level of evidence BData derived from a single randomized clinical trial or large non-randomized studies
      Level of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registries

      Task Force 1: Peri-operative Care of the Heart Transplant Recipient

      Chair: Kumud Dhital
      Co-Chair: Estela Azeka
      Contributing Writers: Monica Colvin, Eugene DePasquale, Marta Farrero, Luis García-Guereta, Gina Jamero, Kiran Khush, Stephanie Pouch, Jacob Lavee, CJ Michaud, Jignesh Patel

      Topic 1: Pre-Transplant Optimization

      Frailty Assessment

      There is an important interplay between frailty and heart failure (HF). Frailty is an independent predictor for the development of HF.
      • Khan H
      • Kalogeropoulos AP
      • Georgiopoulou VV
      • Newman AB
      • Harris TB
      • Rodondi N
      • Bauer DC
      • Kritchevsky SB
      • Butler J
      Frailty and risk for heart failure in older adults: The health, aging, and body composition study.
      However, frailty is also associated with increased mortality and morbidity in the elderly and general HF population. The prevalence of frailty is high in advanced HF patients, accounting for over 30% amongst those referred for advanced HF therapies, including heart transplantation (HT). It is an independent prognostic factor for morbidity and mortality, especially in patients with lower peak oxygen consumption (VO2).
      • Moayedi Y
      • Duero Posada JG
      • Foroutan F
      • Goldraich LA
      • Alba AC
      • MacIver J
      • Ross HJ
      The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.
      A variety of methods have been utilized to assess frailty in HF with increasing support for its value in assessing HT patients. Currently, the modified Fried frailty criteria with five physical domains (fatigue, hand grip strength, gait speed, unintended weight loss and physical activity) and additional cognitive assessment (Montreal Cognitive Assessment [MoCA] tool) appears to be a reasonable resource for HT candidates.
      • Jha SR
      • Hannu MK
      • Chang S
      • Montgomery E
      • Harkess M
      • Wilhelm K
      • Hayward CS
      • Jabbour A
      • Spratt PM
      • Newton P
      • Davidson PM
      • Macdonald PS.
      The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.
      While frailty is associated with increased morbidity and mortality in patients undergoing ventricular assist device (VAD) implantation and HT, it is also largely reversible following these procedures.
      • Jha SR
      • Hannu MK
      • Chang S
      • Montgomery E
      • Harkess M
      • Wilhelm K
      • Hayward CS
      • Jabbour A
      • Spratt PM
      • Newton P
      • Davidson PM
      • Macdonald PS.
      The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.
      • Chung CJ
      • Wu C
      • Jones M
      • Kato TS
      • Dam TT
      • Givens RC
      • Templeton DL
      • Maurer MS
      • Naka Y
      • Takayama H
      • Mancini DM
      • Schulze PC.
      Reduced Handgrip Strength as a Marker of Frailty Predicts Clinical Outcomes in Patients With Heart Failure Undergoing Ventricular Assist Device Placement.
      • Macdonald PS
      • Gorrie N
      • Brennan X
      • Aili SR
      • De Silva R
      • Jha SR
      • Fritis-Lamora R
      • Montgomery E
      • Wilhelm K
      • Pierce R
      • Lam F
      • Schnegg B
      • Hayward C
      • Jabbour A
      • Kotlyar E
      • Muthiah K
      • Keogh AM
      • Granger E
      • Connellan M
      • Watson A
      • Iyer A
      • Jansz PC
      The impact of frailty on mortality after heart transplantation.

      Nutritional Assessment and Rehabilitation

      Prevalence of malnutrition in the heart failure population is high and represents an independent predictor of poor outcome and mortality.
      • Aggarwal A
      • Kumar A
      • Gregory MP
      • Blair C
      • Pauwaa S
      • Tatooles AJ
      • Pappas PS
      • Bhat G.
      Nutrition Assessment in Advanced Heart Failure Patients Evaluated for Ventricular Assist Devices or Cardiac Transplantation.
      Pre transplant body mass index (BMI) is a factor that has been shown to correlate with survival post heart transplant. A United Network for Organ Sharing (UNOS) registry study showed the relationship between BMI and post-transplant survival to be U-shaped, with transplant candidates who were underweight (BMI <18.5 kg/m2) and candidates who were obese (BMI > 35 kg/m2) having significantly decreased survival from year 1 to 5.
      • Russo MJ
      • Hong KN
      • Davies RR
      • Chen JM
      • Mancini DM
      • Oz MC
      • Rose EA
      • Gelijns A
      • Naka Y.
      The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?.
      It is important to note, however, that in regards to nutritional screening and assessment of patients with heart failure, the accuracy of any single nutritional indicator may be compromised by many confounding factors, especially be edema. Edema is caused by fluid retention in addition to inflammatory responses, induced by cytoprotective responses to cellular damage caused by under perfusion of peripheral tissues. Both fluid retention and the inflammatory response affect anthropometric measures such as BMI, triceps skinfold measurement and mid-arm circumference, as well as serum markers, such as albumin and prealbumin. Given secondary confounding factors, multidimensional tools should be used to assess nutrition status.
      • Aggarwal A
      • Kumar A
      • Gregory MP
      • Blair C
      • Pauwaa S
      • Tatooles AJ
      • Pappas PS
      • Bhat G.
      Nutrition Assessment in Advanced Heart Failure Patients Evaluated for Ventricular Assist Devices or Cardiac Transplantation.
      ,
      • Barge-Caballero E
      • García-López F
      • Marzoa-Rivas R
      • Barge-Caballero G
      • Couto-Mallón D
      • Paniagua-Martín MJ
      • Solla-Buceta M
      • Velasco-Sierra C
      • Pita-Gutiérrez F
      • Herrera-Noreña JM
      • Cuenca-Castillo JJ
      • Vázquez-Rodríguez JM
      • Crespo-Leiro MG
      Prognostic Value of the Nutritional Risk Index in Heart Transplant Recipients.
      ,
      • Lin H
      • Zhang H
      • Lin Z
      • Li X
      • Kong X
      • Sun G.
      Review of nutritional screening and assessment tools and clinical outcomes in heart failure.
      Based on a systematic review of literature, the most commonly used tools that provide scores that were independent prognostic factors for mortality risk in heart failure patients, were the Mini Nutrinritional Assessment, MNA-short form, Nutritional Risk Index, and Geriatric Nutritional Risk Index.
      • Lin H
      • Zhang H
      • Lin Z
      • Li X
      • Kong X
      • Sun G.
      Review of nutritional screening and assessment tools and clinical outcomes in heart failure.
      Preliminary studies regarding prehabilitation, exercise, and nutrition interventions prior to surgery have shown promising results with improved outcomes post-surgery.
      • West MA
      • Wischmeyer PE
      • Grocott MPW.
      Prehabilitation and Nutritional Support to Improve Perioperative Outcomes.
      Interventions may include strategies to: 1) improve appetite, such as appetite stimulating agents, including megestrol acetate and anabolic steroids; 2) augment caloric intake, including oral food supplements, or with enteral feedings via nasogastric feeding tube, or percutaneous endoscopic gastrostomy; and 3) directly provide micronutrients, carbohydrates and proteins, such as total parental nutrition.
      • Russo MJ
      • Hong KN
      • Davies RR
      • Chen JM
      • Mancini DM
      • Oz MC
      • Rose EA
      • Gelijns A
      • Naka Y.
      The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?.
      Lastly, post-transplant patients are at high risk for osteopenia and osteoporosis, largely due to use of glucocorticoids and calcineurin inhibitors. Transplant candidates should therefore be evaluated for bone disease by bone marrow density (BMD) and parameters of bone and mineral metabolism, so that appropriate therapies, such as vitamin D supplementation and bisphosphonates, can be initiated to minimize patient's risk for osteopenia following transplant.
      • Kulak CA
      • Borba VZ
      • Kulak Jr., J
      • Custodio MR
      Osteoporosis after transplantation.
      ,
      • Rahman A
      • Jafry S
      • Jeejeebhoy K
      • Nagpal AD
      • Pisani B
      • Agarwala R.
      Malnutrition and Cachexia in Heart Failure.
      Cardiac rehabilitation has been shown to improve functional capacity and decrease hospital readmissions in HF patients, and is currently recommended by guidelines.
      • Piepoli MF
      • Conraads V
      • Corra U
      • Dickstein K
      • Francis DP
      • Jaarsma T
      • McMurray J
      • Pieske B
      • Piotrowicz E
      • Schmid JP
      • Anker SD
      • Solal AC
      • Filippatos GS
      • Hoes AW
      • Gielen S
      • Giannuzzi P
      • Ponikowski PP.
      Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation.
      ,
      • Ponikowski P
      • Voors AA
      • Anker SD
      • Bueno H
      • Cleland JGF
      • Coats AJS
      • Falk V
      • Gonzalez-Juanatey JR
      • Harjola VP
      • Jankowska EA
      • Jessup M
      • Linde C
      • Nihoyannopoulos P
      • Parissis JT
      • Pieske B
      • Riley JP
      • Rosano GMC
      • Ruilope LM
      • Ruschitzka F
      • Rutten FH
      • van der Meer P
      • Group ESCSD.
      2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
      Pre habilitation has been shown to decrease post-operative complication after cardiovascular or abdominal surgery.
      • Barberan-Garcia A
      • Ubre M
      • Roca J
      • Lacy AM
      • Burgos F
      • Risco R
      • Momblan D
      • Balust J
      • Blanco I
      • Martinez-Palli G.
      Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial.
      ,
      • Drudi LM
      • Tat J
      • Ades M
      • Mata J
      • Landry T
      • MacKenzie KS
      • Steinmetz OK
      • Gill HL.
      Preoperative Exercise Rehabilitation in Cardiac and Vascular Interventions.
      Physical activity was related to increased event-free survival on the HT waiting list
      • Spaderna H
      • Vogele C
      • Barten MJ
      • Smits JMA
      • Bunyamin V
      • Weidner G.
      Physical activity and depression predict event-free survival in heart transplant candidates.
      and better functional capacity and health-related quality of life in heart failure, heart transplant or left ventricular assist device (LVAD) patients.
      • Karapolat H
      • Engin C
      • Eroglu M
      • Yagdi T
      • Zoghi M
      • Nalbantgil S
      • Durmaz B
      • Kirazli Y
      • Ozbaran M.
      Efficacy of the cardiac rehabilitation program in patients with end-stage heart failure, heart transplant patients, and left ventricular assist device recipients.

      Psychosocial and Behavioral Optimization

      Pre-transplant psychosocial factors, including patients’ history of medical adherence, mental health, substance use, and social support, can predict outcomes following heart transplantation. Certain factors, such as noncompliance to medical regimen, smoking and alcohol abuse, psychiatric conditions such as depression, and minimal or no social support, have been shown to lead to behaviors of continued or relapse of nonadherence to medical regimen, relapse of substance use, poor self-care, and poor coping. These behaviors lead to poor health-related quality of life with increased morbidity and mortality post-transplant. To maximize outcomes, efforts should be made, prior to transplant, to optimize factors that are modifiable, based on pre-transplant psychosocial evaluation. Interventions may include support groups for substance use, ongoing counseling or therapy, optimization of medical therapy for psychiatric illnesses, and utilization of community resources.
      • Dew MA
      • DiMartini AF
      • Dobbels F
      • Grady KL
      • Jowsey-Gregoire SG
      • Kaan A
      • Kendall K
      • Young Q-R
      • Abbey SE
      • Butt Z
      • Crone CC
      • De Geest S
      • Doligalski CT
      • Kugler C
      • McDonald L
      • Ohler L
      • Painter L
      • Petty MG
      • Robson D
      • Schlöglhofer T
      • Schneekloth TD
      • Singer JP
      • Smith PJ
      • Spaderna H
      • Teuteberg JJ
      • Yusen RD
      • Zimbrean PC.
      The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support.

      Hemodynamic Optimization

      The presence of pre-transplant pulmonary hypertension (PH) in heart organ recipients increases the risk of post-transplant PH and deterioration in right ventricular function in the donor heart. Large registry studies show pre-transplant PH is associated with significantly worse short-term survival post HT compared to patients without pre-transplant PH.
      • Crawford TC
      • Leary PJ
      • Fraser CD
      • Suarez-Pierre A
      • Magruder JT
      • Baumgartner WA
      • Zehr KJ
      • Whitman GJ
      • Masri SC
      • Sheikh F
      • De Marco T
      • Maron BA
      • Sharma K
      • Gilotra NA
      • Russell SD
      • Houston BA
      • Ramu B
      • Tedford RJ.
      Impact of the New Pulmonary Hypertension Definition on Heart Transplant Outcomes.
      ,
      • Yost G
      • Gregory M
      • Bhat G
      Short-Form Nutrition Assessment in Patients With Advanced Heart Failure Evaluated for Ventricular Assist Device Placement or Cardiac Transplantation.
      However, assessment of isolated pulmonary hypertension, related to left ventricular failure and reversibility following transplant, remains challenging. In 2018, the 6th World Health Symposium on Pulmonary Hypertension developed two main changes in the definition and classification of PH.
      • Tedford RJ
      • Beaty CA
      • Mathai SC
      • Kolb TM
      • Damico R
      • Hassoun PM
      • Leary PJ
      • Kass DA
      • Shah AS
      Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.
      First, PH is defined by a mean PAP (mPAP) greater than 20mmHg (previously greater than 25mmHg). The lower parameter reflects recent studies suggesting that individuals with mPAP 21-24mmHg are at increased risk of poor outcomes and tend to progress to “overt PH” (mPAP 25 or greater) more often than patients with lower mPAP(20mmHg or less).
      • Condon DF
      • Nickel NP
      • Anderson R
      • Mirza S
      • de Jesus
      • Perez VA.
      The 6th World Symposium on Pulmonary Hypertension: what's old is new.
      ,
      • Tsukashita M
      • Takayama H
      • Takeda K
      • Han J
      • Colombo PC
      • Yuzefpolskaya M
      • Topkara VK
      • Garan AR
      • Mancini DM
      • Kurlansky PA
      • Naka Y.
      Effect of pulmonary vascular resistance before left ventricular assist device implantation on short- and long-term post-transplant survival.
      In addition, PH was further subclassified by pulmonary vascular resistance (PVR) to help stratify pre-capillary PH (as seen in PAH), and isolated post-capillary PH (IpcPH, related to left ventricle (LV) dysfunction, as well as combined pre- and post- capillary PH (CpcPH) (Table 1). While subcategorization and method of detecting CpcPH remains controversial, current evidence suggests that CpcPH is a distinct entity from PAH or IpcPH and carries a different prognosis both before and after HT.
      • Tedford RJ
      • Beaty CA
      • Mathai SC
      • Kolb TM
      • Damico R
      • Hassoun PM
      • Leary PJ
      • Kass DA
      • Shah AS
      Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.
      ,
      • Vakil K
      • Duval S
      • Sharma A
      • Adabag S
      • Abidi KS
      • Taimeh Z
      • Colvin-Adams M.
      Impact of pre-transplant pulmonary hypertension on survival after heart transplantation: A UNOS registry analysis.
      Table 1Hemodynamic profiles of pulmonary hypertension
      ClassificationMean pulmonary artery pressurePulmonary capillary wedge pressurePulmonary vascular resistance
      Isolated pre-capillary PH>20 mm Hg<15 mm Hg>3 WU
      Combined pre- and post-capillary PH>15 mm Hg>3 WU
      Isolated post-capillary PH>15 mm Hg<3 WU
      Right heart catheterization should be performed on all adult candidates in preparation for listing, and periodically when patients are listed.
      • Mehra MR
      • Canter CE
      • Hannan MM
      • Semigran MJ
      • Uber PA
      • Baran DA
      • Danziger-Isakov L
      • Kirklin JK
      • Kirk R
      • Kushwaha SS
      • Lund LH
      • Potena L
      • Ross HJ
      • Taylor DO
      • Verschuuren EAM
      • Zuckermann A.
      The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update.
      Strategies to assess and optimize elevated pulmonary artery (PA) pressures should be utilized to determine reversibility in order to prevent right ventricular failure post-transplant (Figure 1). Medical therapies include diuretics, inotropes, and vasoactive agents, both inhaled (i.e., nitric oxide and prostacyclins), and intravenous (i.e., nitroglycerin and nitroprusside). Phosphodiesterase-3 (PDE-3) inhibitors (i.e., milrinone) have shown immediate hemodynamic effects, however, with no long-term effects on clinical outcomes in PH due to LV failure. Other therapies typically used for WHO Group 1 PH (pulmonary arterial hypertension) have been utilized for WHO group 2 PH (due to LV failure) with varying results. PDE-5 inhibitors (i.e., sildenafil) has demonstrated some beneficial effects. Additionally, endothelin receptor antagonists (ERAs) such as bosentan and tezosentan have shown some improvement in hemodynamics in pre-clinical and small studies albeit with adverse effects, including hepatic dysfunction. Newer ERAs, such as macetentan, without adverse effects on hepatic function are currently being studied. Finally, PH refractory to medical therapy has been effectively treated with mechanical circulatory support, such as LVADs, with improvement in PH and successful bridging to transplant.
      • Koulova A
      • Gass AL
      • Patibandla S
      • Gupta CA
      • Aronow WS
      • Lanier GM
      Management of pulmonary hypertension from left heart disease in candidates for orthotopic heart transplantation.
      Figure 1:
      Figure 1Established effects of some targeted interventions. Blue bars symbolize depleting or reducing effect. Anti-CD20 antibodies show strong effect on naïve, effector, and memory B cells but no effect on plasma cells, which are not expressing CD20. Proteasome inhibitors show strong effect on PC and moderate effect on memory B cells. Anti-CD19 cells target PC but are currently not available as an effective clinical therapeutic for transplant. Effect of all of these therapies on LLPC is unclear but appears to be limited. (IL: interleukin, LLPC: long lives plasma cell, PC: plasma cell)

      Consideration of mechanical circulatory support (MCS) for Bridging to Transplant

      Patients with HF refractory to optimal medical therapy, with hemodynamic instability and/or progressive end organ dysfunction, should be considered for short-term and/or long-term MCS. MCS therapy should be directed by the trajectory of HF progression and clinical status.
      • den Uil CA
      • Akin S
      • Jewbali LS
      • dos Reis Miranda D
      • Brugts JJ
      • Constantinescu AA
      • Kappetein AP
      • Caliskan K
      Short-term mechanical circulatory support as a bridge to durable left ventricular assist device implantation in refractory cardiogenic shock: a systematic review and meta-analysis.
      • Feldman D
      • Pamboukian SV
      • Teuteberg JJ
      • Birks E
      • Lietz K
      • Moore SA
      • Morgan JA
      • Arabia F
      • Bauman ME
      • Buchholz HW
      • Deng M
      • Dickstein ML
      • El-Banayosy A
      • Elliot T
      • Goldstein DJ
      • Grady KL
      • Jones K
      • Hryniewicz K
      • John R
      • Kaan A
      • Kusne S
      • Loebe M
      • Massicotte MP
      • Moazami N
      • Mohacsi P
      • Mooney M
      • Nelson T
      • Pagani F
      • Perry W
      • Potapov EV
      • Eduardo Rame J
      • Russell SD
      • Sorensen EN
      • Sun B
      • Strueber M
      • Mangi AA
      • Petty MG
      • Rogers J
      International Society for H and Lung T. The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary.
      • Nagpal AD
      • Singal RK
      • Arora RC
      • Lamarche Y.
      Temporary Mechanical Circulatory Support in Cardiac Critical Care: A State of the Art Review and Algorithm for Device Selection.
      • Peura JL
      • Colvin-Adams M
      • Francis GS
      • Grady KL
      • Hoffman TM
      • Jessup M
      • John R
      • Kiernan MS
      • Mitchell JE
      • O'Connell JB
      • Pagani FD
      • Petty M
      • Ravichandran P
      • Rogers JG
      • Semigran MJ
      • Toole JM.
      Recommendations for the Use of Mechanical Circulatory Support: Device Strategies and Patient Selection: A Scientific Statement From the American Heart Association.
      • Potapov EV
      • Antonides C
      • Crespo-Leiro MG
      • Combes A
      • Färber G
      • Hannan MM
      • Kukucka M
      • de Jonge N
      • Loforte A
      • Lund LH
      • Mohacsi P
      • Morshuis M
      • Netuka I
      • Özbaran M
      • Pappalardo F
      • Scandroglio AM
      • Schweiger M
      • Tsui S
      • Zimpfer D
      • Gustafsson F.
      2019 EACTS Expert Consensus on long-term mechanical circulatory support.
      • Rihal CS
      • Naidu SS
      • Givertz MM
      • Szeto WY
      • Burke JA
      • Kapur NK
      • Kern M
      • Garratt KN
      • Goldstein JA
      • Dimas V
      • Tu T
      Society for Cardiovascular A, Interventions, Heart Failure Society of A, Society of Thoracic S, American Heart A and American College of C. 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care: Endorsed by the American Heart Assocation, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d'intervention.
      • Sánchez-Enrique C
      • Jorde UP
      • González-Costello J
      Heart Transplant and Mechanical Circulatory Support in Patients With Advanced Heart Failure.

      Impact of Pediatric Risk Models on Wait-list Management

      Selection of pediatric recipients is a multifactorial process including specific considerations of factors that will directly impact posttransplant outcome. Furthermore, the spectrum of advanced therapies as well as donor polices, public initiatives and published studies have significantly changed approaches in the management and care of this special population. Candidate selection and waitlist removal are a multidisciplinary process that balances the risks and benefits for the transplant procedure.
      • Chen CK
      • Manlhiot C
      • Mital S
      • Schwartz SM
      • Van Arsdell GS
      • Caldarone C
      • McCrindle BW
      • Dipchand AI
      Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.
      ,
      • Peng D
      • Schumacher K.
      Risk factors for early and late mortality in pediatric heart transplantation.
      Pediatric risk factor models have been studied in early and late mortality.
      • Chen CK
      • Manlhiot C
      • Mital S
      • Schwartz SM
      • Van Arsdell GS
      • Caldarone C
      • McCrindle BW
      • Dipchand AI
      Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.
      Risk factors for early mortality include: recipient variables such as diagnosis, age, gender, sensitization, pulmonary vascular resistance, non-cardiac end organ status, mechanical ventilation, extracorporeal membrane oxygenation, VADs; donor-related factors including ischemic time, donor graft function, cause of death. Small center volume has been described as a potential variable for increased post-transplant mortality. A model for in-hospital mortality after pediatric transplantation has been studied using variables available in Organ Procurement Transplantation Network (OPTN) which includes hemodynamic support; Extracorporeal Membrane Oxygenation (ECMO), VAD, ventilator and medical therapy, cardiac diagnosis, renal dysfunction, and serum total bilirubin. This model has C-statistics of 0.75 and 0.81.
      • Almond CS
      • Gauvreau K
      • Canter CE
      • Rajagopal SK
      • Piercey GE
      • Singh TP.
      A Risk-Prediction Model for In-Hospital Mortality After Heart Transplantation in US Children: Risk Prediction in Pediatric Heart Transplant.
      The risk factor model using donor variables on 1-year or late mortality post-transplant has been studied using the OPTN registry
      • Zafar F
      • Jaquiss RD
      • Almond CS
      • Lorts A
      • Chin C
      • Rizwan R
      • Bryant R
      • Tweddell JS
      • Morales DLS.
      Pediatric Heart Donor Assessment Tool (PH-DAT): A novel donor risk scoring system to predict 1-year mortality in pediatric heart transplantation.
      including ischemic time, stroke as the cause of death, donor-to recipient height ratio, donor left ventricular ejection fraction, and donor glomerular filtration rate. This model can be useful when assessing acceptability of a prospective organ in a recipient. Therefore, risk factors models can provide an impact on wait list management after acknowledgement of unmeasured and confounding factors.

      Nutritional Assessment, Nutritional Rehabilitation and Nutritional Interventions in the Pediatric Population

      Nutritional status in most pediatric chronic conditions is a major determinant of childhood well-being. Chronic HF in children is a major cause of malnutrition.
      • Godown J
      • Friedland-Little JM
      • Gajarski RJ
      • Yu S
      • Donohue JE
      • Schumacher KR.
      Abnormal nutrition affects waitlist mortality in infants awaiting heart transplant.
      • Heuschkel RB
      • Gottrand F
      • Devarajan K
      • Poole H
      • Callan J
      • Dias JA
      • Karkelis S
      • Papadopoulou A
      • Husby S
      • Ruemmele F
      • Schäppi MG
      • Wilschanski M
      • Lionetti P
      • Orel R
      • Tovar J
      • Thapar N
      • Vandenplas Y.
      ESPGHAN Position Paper on Management of Percutaneous Endoscopic Gastrostomy in Children and Adolescents.
      • Kirk R
      • Dipchand AI
      • Rosenthal DN
      • Addonizio L
      • Burch M
      • Chrisant M
      • Dubin A
      • Everitt M
      • Gajarski R
      • Mertens L
      • Miyamoto S
      • Morales D
      • Pahl E
      • Shaddy R
      • Towbin J
      • Weintraub R.
      The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary.
      • Schwarz SM
      • Gewitz MH
      • See CC
      • Berezin S
      • Glassman MS
      • Medow CM
      • Fish BC
      • Newman LJ.
      Enteral nutrition in infants with congenital heart disease and growth failure.
      • Spillane NT
      • Kashyap S
      • Bateman D
      • Weindler M
      • Krishnamurthy G.
      Comparison of Feeding Strategies for Infants With Hypoplastic Left Heart Syndrome: A Randomized Controlled Trial.
      Malnutrition is an imbalance of nutrients between intake and nutritional requirements. The body is unable to meet metabolic demands in the setting of cardiac dysfunction. The pathophysiology of heart failure involves activation of compensatory pathways, pro-inflammatory cytokines, neurohormonal abnormalities, increased metabolic demands, reduced intake, and malabsorption.
      • Lewis KD
      • Conway J
      • Cunningham C
      • Larsen BMK.
      Optimizing Nutrition in Pediatric Heart Failure: The Crisis Is Over and Now It's Time to Feed.
      These mechanisms lead to starvation, malabsorption nutritional loss and hypermetabolism which result in malnutrition and suboptimal growth. Therefore, it is recommended that nutritional status should be addressed by history, and nutritional and physical assessment. The basic tools for initial evaluation include a history of energy, protein and fluid intake, weight, length, head circumference measurements on sex- and age- specific growth curves
      • Lewis KD
      • Conway J
      • Cunningham C
      • Larsen BMK.
      Optimizing Nutrition in Pediatric Heart Failure: The Crisis Is Over and Now It's Time to Feed.
      , (weight for age, length for age, body mass index) on which individual patient's values can be plotted and detection of growth velocity deviation. Nutritional support includes hypercaloric feeds, oral supplements, and enteral and parenteral nutrition. Enteral nutrition is required when oral intake is insufficient. Conditions such as severe cord dysfunction, dysphagia, or oral aversion can interfere with adequate oral intake. Nasojejunal tube feeds may be used when nasogastric tube feeds are not tolerated. Nutritional support via gastrostomy can be effective at reversing malnutrition, in maintaining nutritional status, and may be indicated in children requiring prolonged enteral tube feeding. Multidisciplinary discussions surrounding the risk of surgical intervention and anesthesia are required in these cases.

      Consideration of Bridge to Transplant with MCS in Pediatric Recipients

      The use of VADs in pediatric patients for the treatment of advanced HF has increased significantly in the past decade and has supplanted ECMO as the most common form of MCS as a bridge to HT. The percentage of children with MCS as a bridge to transplantation has increased from 25% in 2010 to 36% in 2019. The majority of MCS implants in the pediatric population are INTERMACS profiles 1 or 2 with significantly decreased waitlist mortality. However, the ISHLT registry data demonstrates no survival difference between children with or without VAD support, except for worse outcomes in those bridged with ECMO.
      • Davies RR
      • Haldeman S
      • McCulloch MA
      • Pizarro C.
      Creation of a Quantitative Score to Predict the Need for Mechanical Support in Children Awaiting Heart Transplant.
      • Morales DLS
      • Rossano JW
      • VanderPluym C
      • Lorts A
      • Cantor R
      • St. Louis JD
      • Koeh D
      • Sutcliffe DL
      • Adachi I
      • Kirklin JK
      • Rosenthal DN
      • Blume ED
      Third Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: Preimplant Characteristics and Outcomes.
      • Rossano JW
      • Singh TP
      • Cherikh WS
      • Chambers DC
      • Harhay MO
      • Hayes D
      • Hsich E
      • Khush KK
      • Meiser B
      • Potena L
      • Toll AE
      • Sadavarte A
      • Zuckermann A
      • Stehlik J.
      The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Twenty-second pediatric heart transplantation report –2019; Focus theme: Donor and recipient size match.
      • Yarlagadda VV
      • Maeda K
      • Zhang Y
      • Chen S
      • Dykes JC
      • Gowen MA
      • Shuttleworth P
      • Murray JM
      • Shin AY
      • Reinhartz O
      • Rosenthal DN
      • McElhinney DB
      • Almond CS
      Temporary Circulatory Support in U.S. Children Awaiting Heart Transplantation.

      Pre-Transplant Vaccinations in Adult & Pediatric Candidates for Heart Transplantation

      There are limited data specifically addressing vaccination of adults and children with advanced HF in the pre-transplant setting.
      • Mehra MR
      • Canter CE
      • Hannan MM
      • Semigran MJ
      • Uber PA
      • Baran DA
      • Danziger-Isakov L
      • Kirklin JK
      • Kirk R
      • Kushwaha SS
      • Lund LH
      • Potena L
      • Ross HJ
      • Taylor DO
      • Verschuuren EAM
      • Zuckermann A.
      The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update.
      ,
      • Kirk R
      • Dipchand AI
      • Rosenthal DN
      • Addonizio L
      • Burch M
      • Chrisant M
      • Dubin A
      • Everitt M
      • Gajarski R
      • Mertens L
      • Miyamoto S
      • Morales D
      • Pahl E
      • Shaddy R
      • Towbin J
      • Weintraub R.
      The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary.
      ,
      World Health Organization: Immunization
      Vaccines, and Biologicals.
      • Danziger-Isakov L
      • Kumar D
      • TAICo Practice
      Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice.
      • Rubin LG
      • Levin MJ
      • Ljungman P
      • Davies EG
      • Avery R
      • Tomblyn M
      • Bousvaros A
      • Dhanireddy S
      • Sung L
      • Keyserling H
      • Kang I.
      Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host.
      Tabled 1
      Topic 1: Pre-Transplant Optimization
      2010 Prior Guideline Recommendation2021 Update Guideline Recommendation
      New RecommendationAssessment of frailty using the modified Fried's criteria (3 of 5 possible symptoms, including unintentional weight loss of >10 pounds within the past year, muscle loss, fatigue, slow walking speed, and low levels of physical activity) should be considered when assessing candidacy.

      Class I, Level of Evidence C
      New RecommendationMultidimensional nutritional assessment tools should be used to evaluate heart transplant candidates for malnutrition or for being at risk for malnutrition.

      Class I, Level of Evidence C
      New RecommendationCardiac rehabilitation is reasonable in patients awaiting heart transplantation in order to decrease readmissions, wait list mortality and improve post-transplant outcomes.

      Class IIa, Level of Evidence C
      New RecommendationVarious interventions, such as oral/enteral supplementation, appetite stimulants, micronutrient replacement, and anabolic steroids may be beneficial in optimizing nutritional status prior to transplant to help decrease adverse outcomes including mortality post transplant.

      Class IIa, Level of Evidence C
      New RecommendationBased on psychosocial and behavioral evaluation at time of heart transplant evaluation, interventions and therapies should be initiated to address psychosocial and behavioral risk factors that may contribute to poor outcomes post-transplant.

      Class I Level of Evidence C.
      New RecommendationA vasodilator challenge should be administered when the pulmonary artery systolic pressure is >= 50 mm Hg and either the transpulmonary gradient is >= 15 or the pulmonary vascular resistance (PVR) is > 3Wood units while maintaining a systolic arterial blood pressure > 85 mm Hg.

      Class I, Level of Evidence C
      New RecommendationWhen an acute vasodilator challenge is unsuccessful, hospitalization with continuous hemodynamic monitoring should be performed, as often the PVR will decline after 24 to 48 hours of treatment consisting of diuretics, inotropes, and vasoactive agents, including inhaled nitric oxide.

      Class I, Level of Evidence C
      New RecommendationFollowing bridging left ventricular assist device (LVAD) implantation, re-evaluation of hemodynamics, particularly in respect of the Trans-Pulmonary Gradient (TPG) and PVR is reasonable to be done after 3 months and at regular intervals thereafter to ascertain reversibility of pulmonary hypertension.

      Class IIa, Level of Evidence C
      New RecommendationIf medical therapy fails to achieve acceptable hemodynamics, and if the left ventricle cannot be effectively unloaded with mechanical adjuncts, including an intra-aortic balloon pump (IABP) and/or mechanical circulatory support (MCS), it may be reasonable to conclude that the pulmonary hypertension is irreversible.

      Class IIb, Level of Evidence C
      New RecommendationIABP and short-term MCS should be considered in patients in cardiogenic shock refractory to medical therapy until hemodynamic parameters and end organ function are stabilized, followed by further consideration of urgent HT or continued +/- upgrade to longer-term MCS as deemed appropriate.

      Class I, Level of Evidence C
      New RecommendationLong-term MCS should be considered in patients: (a) When ventricular function is unlikely to recover soon or has been deemed unrecoverable. (b) Who are inotrope dependent and therefore at high risk for death with ongoing medical management. (c) Who are potential HT candidates, with elevated pulmonary vascular resistance that is considered reversible with left ventricular (LV) decompression. (d) Who are potential HT candidates, with contraindications requiring substantial time to reverse, i.e., cancer, obesity, drug and/or alcohol dependence. (e) With a reversible cardiac disease process that requires substantial time for ventricular recovery. (f) Who are ineligible for HT and where long-term MCS is an option.

      Class I, Level of Evidence C
      New RecommendationPediatric risk models may be reasonable to assist with pediatric wait-list management including the removal of patients who are too sick to undergo and benefit from HT.

      Class IIb, Level of Evidence B
      New RecommendationPediatric transplant recipients plotting below the third percentile (–2 standard deviation) can benefit from further assessment, referral, or intervention for nutrition support.

      Class IIa, Level of Evidence C
      New RecommendationConsideration should be given to address moderate or severe wasting and an elevated weight/height as these findings are independent risk factors for waitlist mortality in young patients aged 0-2 years despite the fact there is no apparent effect of these conditions on post-HT mortality.

      Class IIa, Level of Evidence C
      New RecommendationEnergy and nutrient intake and barriers to intake are reasonable to assess at regular intervals.

      Class IIa, Level of Evidence C
      New RecommendationThe decision to insert a gastrostomy tube is reasonable to be determined by a multidisciplinary team through a holistic consideration of medical, ethical, psychological, and quality-of-life issues.

      Class IIa, Level of Evidence C
      New RecommendationTemporary MCS should be considered for potential or actual transplant candidates at high risk of mortality with medical management alone

      Class I, Level of Evidence C
      New RecommendationTemporary MCS devices permit a longer duration of hemodynamic assistance with superior patient survival when compared to conventional Extracorporeal Membrane Oxygenation (ECMO) therapy. Therefore, MCS should be considered as bridging therapy to pediatric HT in the case of refractory heart failure

      Class I, Level of Evidence A
      New RecommendationBridging ventricular assist device (VAD) rather than ECMO support should be considered in children for better survival to HT.

      Class I, Level of Evidence C
      New RecommendationBased on current technology and availability, paracorporeal devices are recommended for children smaller than 20-25 kg.

      Class I, Level of Evidence C
      New RecommendationECMO support may be used as a bridge to decision-making, as a bridge to VAD therapy, or as a bridge to transplantation in critical situations.

      Class IIa, Level of Evidence C
      New RecommendationPediatric heart failure patients ≤24 months of age and who meet criteria for respiratory syncytial virus prophylaxis should receive palivizumab in accordance with established guidelines.

      Class I, Level of Evidence A
      New RecommendationVaccine history and assessment of seroprotection (as appropriate) should be reviewed prior to listing for heart transplantation. Transplant candidates who are unvaccinated or incompletely vaccinated should receive recommended vaccinations as early as possible, as end-organ failure and iatrogenic immunosuppression may diminish vaccine responses.

      Class I, Level of Evidence C
      New RecommendationIn most situations, live virus vaccines are contraindicated following transplantation. Every attempt should be made to complete live virus vaccines, including MMR, varicella, live attenuated zoster, and rotavirus, prior to transplantation in non-immune patients according to established guidelines. Live virus vaccination should ideally be completed four weeks prior to transplantation.

      Class I, Level of Evidence C
      New RecommendationPrior to transplantation, candidates should receive inactivated vaccines, including but not limited to influenza, pneumococcal, tetanus, pertussis, hepatitis A and B, and human papillomavirus vaccines, in accordance with established guidelines. Inactivated vaccines should ideally be completed two weeks prior to transplantation.

      Class I, Level of Evidence C
      New RecommendationThe recombinant subunit zoster vaccine is preferred over the live-attenuated vaccine for transplant candidates and should be given in accordance with local vaccination guidelines.

      Class IIa, Level of Evidence C

      Topic 2: Surgical Issues Impacting Care in the Immediate Post-Operative Period

      Transplantation of Hearts from Donors with Infection

      Donor-derived disease transmissions are uncommon. However, the decision to utilize organs from donors with documented infection should be made with involvement of the transplant infectious diseases team. The use of organs from hepatitis C viremic donors has been associated with excellent short-term outcomes in HT recipients.
      • Aslam S
      • Grossi P
      • Schlendorf KH
      • Holm AM
      • Woolley AE
      • Blumberg E
      • Mehra MR
      Utilization of hepatitis C virus-infected organ donors in cardiothoracic transplantation: An ISHLT expert consensus statement.
      • Kirk R
      • Dipchand AI
      • Davies RR
      • Miera O
      • Chapman G
      • Conway J
      • Denfield S
      • Gossett JG
      • Johnson J
      • McCulloch M
      • Schweiger M
      • Zimpfer D
      • Ablonczy L
      • Adachi I
      • Albert D
      • Alexander P
      • Amdani S
      • Amodeo A
      • Azeka E
      • Ballweg J
      • Beasley G
      • Bohmer J
      • Butler A
      • Camino M
      • Castro J
      • Chen S
      • Chrisant M
      • Christen U
      • Danziger-Isakov L
      • Das B
      • Everitt M
      • Feingold B
      • Fenton M
      • Garcia-Guereta L
      • Godown J
      • Gupta D
      • Irving C
      • Joong A
      • Kemna M
      • Khulbey SK
      • Kindel S
      • Knecht K
      • Lal AK
      • Lin K
      • Lord K
      • Moller T
      • Nandi D
      • Niesse O
      • Peng DM
      • Perez-Blanco A
      • Punnoose A
      • Reinhardt Z
      • Rosenthal D
      • Scales A
      • Scheel J
      • Shih R
      • Smith J
      • Smits J
      • Thul J
      • Weintraub R
      • Zangwill S
      • Zuckerman WA.
      ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation.
      • Kubak BM
      • Gregson AL
      • Pegues DA
      • Leibowitz MR
      • Carlson M
      • Marelli D
      • Patel J
      • Laks H
      • Kobashigawa JA.
      Use of Hearts Transplanted From Donors With Severe Sepsis and Infectious Deaths.
      • Wolfe CR
      • Ison MG
      • tAIDCo Practice
      Donor-derived infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.
      Transmissions of leukemia, lymphoma, rabies, and other central nervous system infections have been reported from donors with encephalitis of unknown etiology, and such donors should be avoided.
      • Wolfe CR
      • Ison MG
      • tAIDCo Practice
      Donor-derived infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

      Transplantation of Hearts from Donors with Potential Drug Toxicities

      While small single center studies have shown conflicting results with donor use with various drug toxicities in heart transplantation, large retrospective registry studies have demonstrated that use of donors with history of alcohol abuse, cocaine use (active or past), or drug overdose does not have deleterious effects on short- and long-term survival post HT.
      • Durand CM
      • Bowring MG
      • Thomas AG
      • Kucirka LM
      • Massie AB
      • Cameron A
      • Desai NM
      • Sulkowski M
      • Segev DL.
      The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States: A National Registry Study.
      • Ising MS
      • Gallo M
      • Whited WM
      • Slaughter MS
      • Trivedi JR.
      Changing demographics of heart donors: The impact of donor drug intoxication on posttransplant survival.
      • Jacob KA
      • de Heer LM
      • de Heer F
      • Kluin J.
      Chronic alcoholic donors in heart transplantation: A mortality meta-analysis.
      • Jayarajan S
      • Taghavi S
      • Komaroff E
      • Shiose A
      • Schwartz D
      • Hamad E
      • Alvarez R
      • Wheatley G
      • Guy TS
      • Toyoda Y
      Long-term outcomes in heart transplantation using donors with a history of past and present cocaine use†.
      • Taghavi S
      • Jayarajan S
      • Komaroff E
      • Shiose A
      • Schwartz D
      • Hamad E
      • Alvarez R
      • Wheatley G
      • Guy T
      • Toyoda Y
      Use of Heavy Drinking Donors in Heart Transplantation is Not Associated With Worse Short- and Medium-Term Mortality.
      • Warraich HJ
      • Cobb S
      • Lu D
      • Cooper L
      • DeVore A
      • Patel C
      • Rosenberg P
      • Schroder J
      • Daneshmand M
      • Milano C
      • Rogers J
      • Mentz R
      Trends and Outcomes of Cardiac Transplantation From Donors Dying of Drug Intoxication.
      Several case studies show successful transplantation with donors who suffered carbon monoxide poisoning. While safety is not completely established, the use of hearts in these donors can reasonably be considered in the setting of clinical and objective evidence of satisfactory cardiac function.
      • Luckraz H
      • Tsui SS
      • Parameshwar J
      • Wallwork J
      • Large SR.
      Improved outcome with organs from carbon monoxide poisoned donors for intrathoracic transplantation.
      • Martin-Suarez S
      • Mikus E
      • Pilato E
      • Bacchini M
      • Savini C
      • Grigioni F
      • Coccolo F
      • Marinelli G
      • Mikus PM
      • Arpesella G.
      Cardiac transplantation from a carbon monoxide intoxicated donor.
      • Sezgin A
      • Akay TH
      • Ozkan S
      • Gultekin B.
      Successful cardiac transplantation from donor with carbon monoxide intoxication: a case report.

      Use of Donors with Pre-existing Cardiac Abnormalities

      There is data limited to small studies and case reports regarding the use of donors with coronary artery disease (CAD) that demonstrate varying results and effects of donor CAD on post-transplant vasculopathy and overall outcomes.
      • Estevez-Loureiro R
      • Paniagua-Martin MJ
      • Calviño-Santos R
      • Vazquez-Rodríguez JM
      • Salgado-Fernandez J
      • Marzoa-Rivas R
      • Barge-Caballero E
      • Grille Z
      • Pérez-Pérez A
      • Rodríguez-Fernandez JA
      • Vázquez-González N
      • Cuenca-Castillo JJ
      • Castro-Beiras A
      • Crespo-Leiro MG
      Prevalence of Donor-Transmitted Coronary Artery Disease and Its Influence on Heart Transplant Outcomes.
      • Kimura Y
      • Seguchi O
      • Iwasaki K
      • Toda K
      • Kikuchi N
      • Matsuda S
      • Kumai Y
      • Kuroda K
      • Wada K
      • Matsumoto Y
      • Fukushima S
      • Yanase M
      • Fujita T
      • Kobayashi J
      • Fukushima N.
      Impact of Coronary Artery Calcification in the Donor Heart on Transmitted Coronary Artery Disease in Heart Transplant Recipients.
      • Pinto CS
      • Prieto D
      • Antunes MJ.
      Coronary artery bypass graft surgery during heart transplantation.
      • 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