Heart transplant recipients are living longer, requiring clinicians to think beyond graft survival and consider long-term challenges and overall well-being. Focus on initial patient survival metrics often overshadows the significant side effects of immunosuppressive therapy. Recipients struggle to overcome physical deconditioning, psychological distress, and issues associated with social reintegration. These burdens may often be considered an expected part of life with transplantation, yet they deeply affect daily living, self-care, and long-term health outcomes. This article reviews the complex realities of life after heart transplantation and recommends a more holistic, patient-centered model, one that prioritizes not just graft survival, but recovery of function, well-being, and quality of life.

Purpose: Heart failure (HF) is a complex clinical syndrome associated with morbidity and mortality. Identification of independent predictors of risk in HF patients is crucial for guiding proper management strategies. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated tool that assesses the quality of life and functional status in HF patients. Therefore, we aimed to assess the KCCQ's Overall Summary Score (KCCQ-OSS) and independent parameters such as demographics, ejection fraction (EF), and other KCCQ-related variables as predictors of outcome in the study population.

The “International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates—2024” updates and replaces the “Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates—2006” and the “2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update.” The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

Purpose: The development of de novo donor specific antibody (DSA) after heart transplant has been reported to be associated with lower survival, development of cardiac allograft vasculopathy and graft dysfunction. More specifically, those patients with DSA that have the ability to bind complement (C1q+), are reported to have even worse outcome after heart transplant. It is not known whether the treatment of asymptomatic DSA C1q+ is efficacious. In our program, asymptomatic DSA C1q+ have been treated with combinations of IVIG and rituximab per physicians' choice.

Purpose Heart transplant (HTx) candidates may have elevated pulmonary artery (PA) pressures. In many cases, programs may accept only oversized male donor hearts while declining oversized female donor hearts for HTx candidates with pulmonary hypertension (PH). We reviewed our experience with HTx candidate with PH and male vs female donors. . Methods We assessed 118 candidates on the HTx waitlist 2010-2021 with mean PA pressures > 25mmHg or PA systolic > 40mmHg. Oversized donor hearts defined as predicted heart mass (PHM) >1.10. Subgroup analyses included sex mismatch of oversized donor hearts. Outcomes: 30-day and 1-year survival, 30-day freedom from RV dysfunction, and pulmonary artery pressures at 1-, 3-, and 12-months post-transplant. Results Recipients of female vs male oversized donor hearts had comparable outcomes in 30-day and 1-year survival and 30-day freedom from RV dysfunction. (Table 1) PA pressures normalized by 1-year post HTx. When donor hearts were separated by age (≥40 years vs <40 years), there was no difference in outcomes (Table 2). There was no interaction between donor sex and age. Conclusion Female oversized donor hearts by PHM (regardless of donor age) for patients with pulmonary hypertension offer acceptable post-HTx outcomes.

Purpose Sensitized patients undergoing HTx have greater risk of antibody mediated rejection (AMR), cardiac allograft vasculopathy (CAV), and decreased survival. A prospective crossmatch is performed on highly sensitized patients pre-HTx. While a cytotoxicity-positive complement test may be prohibitive for HTx, patients with flow-positive but cytotoxicity-negative crossmatch undergo HTx at our program. We reviewed outcomes of these patients. Methods 60 highly sensitized patients with flow-positive yet cytotoxicity-negative prospective crossmatches 2010-2021 were evaluated. Outcomes assessed: 5-year survival and 5-year freedom from CAV (stenosis ≥40% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, percutaneous intervention, pacemaker, or stroke), and 1-year freedom from rejection [any treated rejection (ATR), acute cellular rejection (ACR), and AMR]. A subgroup was analyzed for the impact to outcome of T-cell and B-cell flow positivity (median channel shifts, MCS >200 and <200) and for Class I vs Class II donor-specific antibodies (DSA). A control group consisted of non-sensitized patients (n=540). Results 5-year survival, freedom from CAV and NF-MACE were comparable between flow-positive cytotoxicity-negative patients and controls. These patients, however, had lower freedom from ATR/AMR (Table). There was also lower freedom from ATR/AMR in those with higher flow MCS though no difference based on Class I vs II DSA. Conclusion Patients with flow-positive cytotoxicity-negative prospective crossmatches have comparable 5-year outcomes to nonsensitized patients. Despite increased ATR, there is no impact on survival or CAV development. These findings support proceeding with transplantation in this high-risk group.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is more prevalent than appreciated in the elderly. We present the case of an 88-year-old woman who underwent heart transplantation for ischemic cardiomyopathy and then presented 21 years later with new onset atrial flutter, found on endomyocardial biopsy to have new ATTRwt-CM. (Level of Difficulty: Advanced.).

Purpose The cardiac allograft vasculopathy (CAV) trajectory score predicts CAV severity and mortality after heart transplantation (HTx). This trajectory score has been helpful to reduce the number of annual coronary angiograms for those low-risk patients who fall into trajectory 1. However, this model has not been validated in multiorgan transplant recipients, specifically heart-kidney transplantation (HKTx). We sought to assess whether the CAV trajectory score also applies to HKTx recipients. Methods We assessed 62 HKTx recipients transplanted between 2010 and 2017 and assigned trajectories based on the CAV trajectory score (1-4). Due to small numbers, patients in trajectory 2-4 scores were combined. Patients were followed for 5 years to assess whether the prediction model was correct for the development of CAV and degree of CAV involvement (CAV1, CAV2, CAV3). Other endpoints included 5-year survival and freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, heart failure, coronary intervention, defibrillator/pacemaker, stroke). Results There was a trend for patients in the trajectory 2-4 group compared to the trajectory 1 group to have lower freedom from 5-year CAV. Patients in trajectory 1 had milder CAV (only CAV1). The 5-year survival and freedom from NF-MACE was comparable between groups. Older age and ACR in the first year were the prominent factors of the trajectory score that determined higher risk. (See table) Conclusion The CAV trajectory score may be accurate for HKTx recipients, though small numbers preclude definitive conclusions. As CAV is mild in HKTx recipients in trajectory 1, it seems reasonable to forego frequent surveillance annual angiograms. Trajectory 2-4 patients should maintain routine annual coronary angiograms.

Purpose Smoking in the potential donor may be a risk factor for the development of cardiac allograft vasculopathy (CAV) following heart transplantation. It has been demonstrated by Loupy and colleagues using the cardiac iBox that donor smoking was an independent factor leading to a high trajectory for developing CAV by coronary angiography. It has not been well established how much donor smoking attributes to this problem. Therefore, we reviewed our experience with donors and their smoking history to assess this post-transplant complication. Methods Between 2010 and 2017, we assessed 678 donors whose heart underwent heart transplantation. Donors were separated into those with smoking history >20 pack-years and continued cigarette use in the past 6 months (data provided from UNOS). Each group was assessed for 1-, 2-, 3-year survival and freedom from the development of coronary angiography-proven evidence of CAV (defined as coronary lesion ≥30% stenosis). This study group was compared to a control group with no donor smoking history. Results Donors with a current 20 pack-year smoking history compared to those donors without smoking had a trend for an increased risk for the development of CAV on coronary angiography over 3 years. 1-, 2-, 3-year survival was similar in both groups. Conclusion Active donor smoking history appears to be a potential risk factor for the development of CAV. Longer follow-up is needed to further define this risk.

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(Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7a, Table 7b, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14) Table 1Hemodynamic profiles of pulmonary hypertension Classification Mean pulmonary artery pressure Pulmonary capillary wedge pressure Pulmonary 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 The 6th World Symposium on Pulmonary Hypertension defined three hemodynamic profiles of pulmonary hypertension (PH): isolated pre-capillary PH, combined. The pre- and post-capillary PH, and isolated post-capillary PH. WU, Wood units). [22] 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. The Journal of Heart and Lung Transplantation. 2014; 33: 289-297 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Open table in a new tab Table 2Predicted Heart Mass Calculator Predicted right ventricular mass(RVM) a × Ag e − 0.32 × Heigh t 1.135 × Weigh t 0.315 where a = 10.59 for women and 11.25 for men Predicted left ventricular mass(LVM) a × Heigh t 0.54 × Weigh t 0.61 where a = 6.82 for women and 8.25 for men Predicted heart mass (PHM) RVM + LVM Body mass index (BMI) Height Weigh t 2 Body surface area (BSA) a × Heigh t 0.725 × Weigh t 0.425 where a = 0.007184 Donor to recipient size match Size metri c donor Size metri c recipient Open table in a new tab Table 3Recommendations for the Prevention of Cytomegalovirus in Heart Transplant Recipients Group Recommendations D+/R- Ganciclovir 5mg/kg IV daily or valganciclovir 900mg po daily* for 3-6 months Preemptive therapy generally not preferred but is an alternate option Some HT centers will add CMV immune globulin for high-risk patients R+ Ganciclovir 5mg/kg IV daily or valganciclovir 900mg po daily* for 3 months Preemptive therapy is an alternate to universal antiviral prophylaxis Open table in a new tab Table 4Recommended mTOR inhibitor & CNI target levels: Adults IS regimen Everolimus (ng/mL) Sirolimus (ng/mL) Cyclosporine (Time post-tx) (ng/mL) Tacrolimus (Time post-tx) (ng/mL) CNI + mTOR inhibitor 3-8 4-12 75-200 (3-6 months)50-100 (> 6 months) 3-8 (> 6 months) CNI-free (e.g., mTOR + MMF) 6-10 8-15 Pediatrics* IS regimen Everolimus (ng/mL) Sirolimus (ng/mL) Cyclosporine (Time post-tx) (ng/mL) Tacrolimus (Time post-tx) (ng/mL) CNI + mTOR inhibitor 3-6 4-7 100-200 (3-6 months)60-120 (> 6 months) 4-8 (> 6 months) CNI-free (e.g., mTOR + MMF) 3-8 5-8 *Aim for higher end of range when using mTOR to intensify immune suppression for CAV prevention in high-risk patients; aim for lower end of range when targeting reduced intensity immune suppression for PTLD, frequent infections, or renal failure. Open table in a new tab Table 5Drugs That Affect the Levels of Tacrolimus, Cyclosporine, Sirolimus, or Everolimus Decrease immunosuppression levels Increase immunosuppression levels Anti-epilepticsCarbamazepineFosphenytoinPhenobarbitalPhenytoin Anti-fungalsClotrimazoleFluconazoleIsavuconazoleItraconazoleKetoconazolePosaconazoleVoriconazole Anti-microbialsCaspofunginNafcillinRifabutinRifampinRifapentine Anti-microbialsClarithromycinErythromycinMetronidazole and tinidazole Anti-retroviral therapyEfavirenzEtravirineNevirapine Anti-retroviral therapyProtease inhibitors (general)CobicistatDarunavirFosamprenavirIndinavirNelfinavirRitonavirSaquinavirTipranavir AntiviralsLetermovir Monoclonal antibodiesTocilizumab Direct acting antivirals for Hepatitis C:DaclatasvirGlecaprevir-PibrentasvirGrazoprevir-ElbasvirLedipasvir-(Sofosbuvir)Velpatasvir-(Sofosbuvir)Voxilaprevir-Velpatasvir-(Sofosbuvir) CardiovascularBosentan CardiovascularAmiodaroneDiltiazemVerapamil OthersAprepitantDeferasiroxModafinilSt. John's wortThalidomideTiclopidine OthersCimetidineFluvoxamineGlipizideGlyburideImatinibNefazodoneRilonaceptTheophyllineTurmeric NutraceuticalsBitter orangeGrapefruit Open table in a new tab Table 6Significant Differences in Primary endpoints between Study Groups from Major Clinical Trials since 2010 Author (year) Study No. Follow-up Survival Rejection CAV by IVUS Barten (2019) MANDELA:EVL/redCNI vsCNI-free 162 1 year NS CNI-free= more rejection NS Potena (2018) EVERHEART:Immediate (≤144 h) (EVL-I) vsdelayed (4-6 weeks post-HTx) (EVL-D) EVL initiation 181 6 months NS EVL-I= higher incidenceBPAR ≥2R(but not SS) NS Arora (2015)Andreassen (2016) SCHEDULE:redCYA/EVL & CNI withdrawal at 7‐11 weeks vsCYA+ MMF 115 1-3 years NS EVL group= more rejection EVL group= less CAV Eisen (2013) CRAD 2310:redCyA/EVL 1.5mg vsredCyA/EVL 3mg (dc) vsCYA/MMF 721 12-24 months NS No significant differences between groups EVL/redCYA group= less CAV Open table in a new tab Table 7ASignificant Differences in Adverse Events from the Major Clinical Trials since 2010 Author (year) Study No. Renal function Infections Cholesterol & triglycerides Hypertension Barten (2019) MANDELA:EVL/redCNI vsCNI-free 162 CNI‐free= better renal function CNI-free= less CMV(? SS, no p-value) - EVL/redCNI= more hypertension(? SS, no p-value) Potena (2018) EVERHEART:Immediate (≤144 h) (EVL-I) vsdelayed (4-6 weeks post-HTx) (EVL-D) EVL initiation 181 comparable between both groups EVL-I= lower risk CMV No significant differences between groups No significant differences between groups Arora (2015)Andreassen (2016) SCHEDULE:redCYA/EVL & CNI withdrawal at 7‐11 weeksvs CYA+ MMF 115 EVL= better renal function No significant differences between groups NS No significant differences between groups Eisen (2013) CRAD 2310:redCyA/EVL 1.5mg vsredCyA/EVL 3mg (dc)vs CYA/MMF 721 EVL/redCYA= inferior for renal function but comparable if predefined redCYA level achieved EVL/redCYA= less CMV EVL/redCYA= higher total cholesterol & HDL= higher LDL & TG at 1 year only No significant differences between groups Open table in a new tab Table 7BSignificant Differences in Adverse Events from the Major Clinical Trials since 2010 Author (year) Study No. Hematologic GI disorders Other Barten (2019) MANDELA:EVL/redCNIvs CNI-free 162 No significant differences between groups EVL/redCNI= more diarrhoea & nausea(? SS, no p-value) - Potena (2018) EVERHEART:Immediate (≤144 h) (EVL-I) vsdelayed (4-6 weeks post-HTx) (EVL-D) EVL initiation 181 No significant differences between groups NS EVL-I= more pericardial effusion= more AEs= more discontinuations due to AEs & serious AEsEVL-I = 48% non-significant increase in the relative risk of incidence of the primary endpoint (postoperative wound healing delays, pericardial effusion, pleural effusion needing drainage and acute renal insufficiency events) Arora (2015)Andreassen (2016) SCHEDULE:redCYA/EVL & CNI withdrawal at 7‐11 weeks vs CYA+ MMF 115 No significant differences between groups - No significant differences between groups for surgical events or wound complications Eisen (2013) CRAD 2310:redCyA/EVL 1.5mg vsredCyA/EVL 3mg (dc)vs CYA/MMF 721 EVL/redCYA = more anemia - EVL 3mg/redCYA arm= enrolment dc due to higher early mortalityEVL/redCYA= more pericardial effusion dc = discontinued; NS = not stated; SS = statistically significant; AE = adverse event Open table in a new tab Table 8Desensitization and AMR and Therapies [400] Sriwattanakomen R Xu Q Demehin M Shullo MA Mangiola M Hickey GW Sciortino CM Horn ET Keebler ME Zeevi A. Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates. J Heart Lung Transplant. 2021; 40: 595-603 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Therapy Mechanism of Action Immune Effects Major Adverse Effects Alemtuzumab CD52 monoclonal antibody Depletes circulating lymphocytes, macrophages and monocytes Leukopenia, thrombocytopenia, infusion related reactions Bortezomib Proteasome inhibitor Depletes plasma cells Peripheral neuropathy, thrombocytopenia, neutropenia Carfilzomib Proteasome inhibitor Depletes plasma cells AKI, thrombocytopenia, cardiotoxicity Eculizumab Complement C5 inhibitor Inhibits formation of terminal complement C5b-9 Meningococcal infection (Vaccination recommended) Intravenous immunoglobulin Immunomodulatory effects Neutralize circulating antibody, inhibit complement, inhibit B cells Infusion-related reactions, hemolysis, interference with antibody assays PIasmapheresis Extracorporeal plasma antibody filtration Removes circulating immunoglobulins Access and line related complications, coagulopathy Rituximab CD20 monoclonal antibody Depletes circulating B cells Infusion-related reactions Splenectomy Removal of secondary lymphoid organ Removes major source of lymphocytes Encapsulated bacterial infections Open table in a new tab Table 9Examples of Therapies for Antibody-Mediated Rejection Therapeutic modality Dose Frequency Duration Plasmapheresis 1-2 plasma exchanges Daily Every other day 3-5 days1-2 weeks 3 times per week 1-4 weeks Once weekly 2-4 weeks IVimmunoglobulin 100 – 2000 mg/kg Low dose 1–3 times per week, often given after each plasmapheresisImmune modulating dose (2g/kg) after last plasmapheresis cycle q 4 weeks 1-4 weeks Rituximab 375 mg/m2 Once weekly 1-4 weeks IV Ig, intravenous immunoglobulin. [218] Open table in a new tab Table 10Recommended Nomenclature for Cardiac Allograft Vasculopathy ISHLT CAV0 (Not significant): No detectable angiographic lesion ISHLT CAV1 (Mild): Angiographic left main (LM) <50%, or primary vessel with maximum lesion of <70%, or any branch stenosis <70% (including diffuse narrowing) without allograft dysfunction ISHLT CAV2 (Moderate): Angiographic LM <50%; a single primary vessel ≥70%, or isolated branch stenosis ≥70% in branches of 2 systems, without allograft dysfunction ISHLT CAV3 (Severe): Angiographic LM ≥50%, or two or more primary vessels ≥70% stenosis, or isolated branch stenosis ≥70% in all 3 systems; or ISHLT CAV1 or CAV2 with allograft dysfunction (defined as LVEF ≤45% usually in the presence of regional wall motion abnormalities) or evidence of significant restrictive physiology (which is common but not specific; see text for definitions) Definitions a). A “Primary Vessel” denotes the proximal and Middle 33% of the left anterior descending artery, the left circumflex, the ramus and the dominant or co-dominant right coronary artery with the posterior descending and posterolateral branches. b). A “Secondary Branch Vessel” includes the distal 33% of the primary vessels or any segment within a large septal perforator, diagonals and obtuse marginal branches or any portion of a non-dominant right coronary artery. c). Restrictive cardiac allograft physiology is defined as symptomatic heart failure with echocardiographic E to A velocity ratio >2 (>1.5 in children), shortened isovolumetric relaxation time (<60 msec), shortened deceleration time (<150 msec), or restrictive hemodynamic values (Right Atrial Pressure >12mmHg, Pulmonary Capillary Wedge Pressure (PCWP) >25 mmHg (>15mmHg in children * Modified PCWP threshold in children based on[273]. ), Cardiac Index <2 l/min/m2) Modified PCWP threshold in children based on [273] Kindel SJ Law YM Chin C Burch M Kirklin JK Naftel DC Pruitt E Carboni MP Arens A Atz AM Dreyer WJ Mahle WT Pahl E. Improved Detection of Cardiac Allograft Vasculopathy: A Multi-Institutional Analysis of Functional Parameters in Pediatric Heart Transplant Recipients. J Am Coll Cardiol. 2015; 66: 547-557 Crossref PubMed Google Scholar . Open table in a new tab Table 11Behavioral, Social, Medical, and Other Factors that Increase Risk for Recent HIV, HBV, or HCV Infection in Organ Donors Sex (i.e., any method of sexual contact, including vaginal, anal, and oral) with a person known or suspected to have HIV, HBV, or HCV infection Man who has had sex with another man Sex in exchange for money or drugs Sex with a person who had sex in exchange for money or drugs Drug injection for nonmedical reasons Sex with a person who injected drugs for nonmedical reasons Incarceration (confinement in jail, prison, or juvenile correction facility) for ≥72 consecutive hours Child breastfed by a mother with HIV infection Child born to a mother with HIV, HBV, or HCV infection Unknown medical or social history Open table in a new tab Table 12Sample * The frequency of follow-up visits for HT recipients will depend on the time from HT and the post-operative clinical course. The frequency of follow-up should be increased if complications occur, particularly in patients with challenging medical or psychosocial conditions. In addition, in view of different local availabilities of newer noninvasive modalities (e.g., Gene Expression Profiling) and the lack of evidence about the optimal timing of echocardiographic studies in HT patients, it should be noted that the frequency of follow-up visits and schedule presented in the table serve merely as an example and should be tailored to each center. Furthermore, as noninvasive modalities improve, it is likely that the need for biopsies and serial conventional angiography will be reduced accordingly. : Follow-up visits and test schedule >5 2-5 1 Year >60 >24 21 18 15 12 11 10 9 8 7 6 5 4 3 2 1 Month 24 20 16 12 10 8 7 6 5 4 3 2 1 Week × × × × × × × × × × × × × × × × × × × HT clinic visit × × × × × × × × × × × × × × × × × × × Lab tests[ [1] 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. American Heart Journal. 2013; 166: 887-894 Crossref PubMed Scopus (0) Google Scholar ] × × × × × × × × × × ECG × × × × × × × × × × × Echo × × × × × × × × × × × × × × B iopsy ²(Other non-invasive methods as appropriate) × × × × × × × Right heart study S tarting in the fifth year – to be done every other year alternating with coronary angiography Dobutamine echo/SPECT/CTA x x × x x × x x × x x × x × × C MV DNA ³ ×4 × Coronary angiography × × × Urine 24h protein × Malignancy screening 4 × × × Chest X-ray × × × PSA x x × × x × PRA (DSA)5 × × × Bone density x x x x CPET x × × × × Skin-cancer screening clinic x x x x Endocrinology clinic x x x x Dental exam The frequency of follow-up visits for HT recipients will depend on the time from HT and the post-operative clinical course. The frequency of follow-up should be increased if complications occur, particularly in patients with challenging medical or psychosocial conditions. In addition, in view of different local availabilities of newer noninvasive modalities (e.g., Gene Expression Profiling) and the lack of evidence about the optimal timing of echocardiographic studies in HT patients, it should be noted that the frequency of follow-up visits and schedule presented in the table serve merely as an example and should be tailored to each center. Furthermore, as noninvasive modalities improve, it is likely that the need for biopsies and serial conventional angiography will be reduced accordingly. Open table in a new tab Table 13Special Anesthetic Considerationsfor Intercurrent Surgery in HT Recipients 833 Barbara DW Christensen JM Mauermann WJ Dearani JA Hyder JA. The Safety of Neuromuscular Blockade Reversal in Patients With Cardiac Transplantation. Transplantation. 2016; 100: 2723-2728 Crossref PubMed Scopus (0) Google Scholar , 834 De Jong FH Mallios C Jansen C Scheck PAE Lamberts SWJ. Etomidate Suppresses Adrenocortical Function by Inhibition of 1 lβ-Hydroxylation. The Journal of Clinical Endocrinology & Metabolism. 1984; 59: 1143-1147 Crossref PubMed Google Scholar , 835 Gronwald C Vowinkel T Hahnenkamp K. Regional anesthetic procedures in immunosuppressed patients: risk of infection. Current Opinion in Anaesthesiology. 2011; 24: 698-704 Crossref PubMed Scopus (0) Google Scholar , 836 Koglin J Gross T Uberfuhr P von Scheidt W. Time-dependent decrease of presynaptic inotropic supersensitivity: physiological evidence of sympathetic reinnervation after heart transplantation. J Heart Lung Transplant. 1997; 16: 621-628 PubMed Google Scholar , 837 Sidi A Kaplan RF Davis RF. Prolonged neuromuscular blockade and ventilatory failure after renal transplantation and cyclosporine. Canadian Journal of Anaesthesia. 1990; 37: 543-548 Crossref PubMed Scopus (0) Google Scholar Special consideration Single dose of etomidate, used during induction, has been shown to decrease serum concentration of cortisol for at least 24 hours. However, this has not been shown to be clinically relevant. Cyclosporine has been described as prolonging muscle relaxants; this effect has not been shown in patients on mycophenolate mofetil and tacrolimus. Although the apparent higher potential for infectious complications of spinal or epidural anesthesia, limited data have not demonstrated this occurrence for regional or neuraxial procedures Given the complete cardiac denervation, drugs that work on the autonomic nervous system have minimal effects on the transplanted heart.Indirect-acting sympathomimetics such as ephedrine are therefore not very effective for treating hypotension and maintaining cardiac output; and ketamine may not display hemodynamic stability in heart transplant patients in extremis.Direct-acting sympathetic agents, like norepinephrine, epinephrine, isoproterenol, and dopamine, are effective, although the beta-adrenergic inotropic effects are attenuated early after HT.Phosphodiesterases have been shown to increase inotropy in the transplanted heart. The alpha-adrenergic response of phenylephrine is effective, but the reflex bradycardia is absent. The indirect acting anticholinergics (atropine, glycopyrrolate) and anticholinesterases (neostigmine, edrophonium) have no effect on the heart rate of the cardiac allograft, and the safety of neuromuscular reversal has been demonstrated in a large-scale study with no instances of severe bradycardia or cardiac arrest.The direct neuromuscular blockade Sugammadex, which directly inhibits neuromuscular blocking agents, is devoid of any direct cholinergic effects, and is a reasonable alternative in HT recipients. Open table in a new tab Table 14Sample Procedures for Pathological examination of the explanted hearts [936] Leone O Angelini A Bruneval P Potena L. The Pathology of Cardiac Transplantation A clinical and pathological perspective. 1. illustrations, 2016: 448 Google Scholar Appropriated photographic documentation of the intact and the sectioned hearts should be performedPreferably before fixation in 10% formalin, sampling of fresh myocardium from the four cavities taking multiple small fragments to be frozen for genetic and molecular analysis, and to be fixed in Karnovsky/glutaraldehyde for electron microscopy for diagnostic and for research purposes.Gross examination before sectioning according to standard protocols, which take into consideration the different types of pathologies, which have led to transplant.Sectioning according to the different types of pathologies:- for cardiomyopathies, ischemic heart disease, and valve diseases transverse cut from apex to the base of the heart.- for congenital heart disease the transverse cut is not recommended but use the sequential segmental approach5) Histological sampling of the entire circumferential midventricular transverse cut and of the coronary arteries for multiple appropriate staining including immunohistochemistry6) In case of mechanical assistance device implantation prior to transplant it would be important to evaluate grossly the device before removing it. In case of interventional procedures, both percutaneous and surgical, on the coronary arteries and on the valves particular care should be adopted for stents, valve, and vascular prosthesis with specific technique. Open table in a new tab The 6th World Symposium on Pulmonary Hypertension defined three hemodynamic profiles of pulmonary hypertension (PH): isolated pre-capillary PH, combined. The pre- and post-capillary PH, and isolated post-capillary PH. WU, Wood units). [22] 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. The Journal of Heart and Lung Transplantation. 2014; 33: 289-297 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar *Aim for higher end of range when using mTOR to intensify immune suppression for CAV prevention in high-risk patients; aim for lower end of range when targeting reduced intensity immune suppression for PTLD, frequent infections, or renal failure. dc = discontinued; NS = not stated; SS = statistically significant; AE = adverse event

Purpose West Nile Virus after heart transplant (HTx) is rare. However, it has occurred in our large, single-center heart transplant program. West Nile Virus is reportedly spread by mosquitoes and has been seen in various areas within the United States. We now report on our experience. Methods Between 2013 and 2017, we assessed 5 HTx patients found to have acquired West Nile Virus after HTx. The outcomes of these patients are now assessed. Endpoints included 1-year subsequent survival, neurologic status, rejections, cardiac function, cardiac allograft vasculopathy (CAV, stenosis ≥30%), and non-fatal major adverse cardiac events (NF-MACE). Results Mortality in this population is 100%. Patients were severely neurologically compromised and completely dependent on 24/7 care. One patient was alert and ambulatory but aspirated on soup, thought to possibly be due to suppressed gag/cough reflex. The patient subsequently died. The other four patients were severely neurologically comprised—all with flaccid paralysis/quadriplegia, although able to communicate by moving eyes, facial gestures, and/or head and lip movement. All patients were able to communicate but were dependent on external feeding. Conclusion West Nile Virus is devastating post-HTx with high mortality and significant morbidity which has left these patients in almost a comatose state.

Purpose The COVID pandemic has affected the management of heart transplant (HTx) patients. Patients were seen virtually via telemedicine and patients self-isolated at home. We assessed the impact of telemedicine and isolation during the COVID pandemic on HTx outcomes at our center. Methods We assessed 55 HTx patients who were transplanted March - September 2020 and followed for 6 months. Patients were self-isolating and only had every other clinic visit in-person after the first month. Outcomes included 6-month survival, re-hospitalization, non-COVID infections (defined as requiring intravenous antibiotics), any treated rejection (ATR), and maintenance of therapeutic immunosuppressive blood levels. The study patients were then compared to a control group of HTx patients evaluated during March of the previous three years. Results The study group (during the COVID pandemic) demonstrated a significant decrease in re-hospitalization in the first 6 months following HTx compared to the control group. There was a numerical decrease in non-COVID infectious complications. There was no difference in survival or freedom from treated rejection episodes between the two groups. Reasons for rehospitalization included infections, cardiac and renal issues, malaise, and fever. Of note, 2 patients in the study group developed COVID subsequently after HTx but were not hospitalized. Conclusion The COVID pandemic demonstrated that self-isolation and virtual visits resulted in less hospitalizations, possibly due to fewer infectious complications. This implies that perhaps stricter restrictions for community exposure might benefit HTx patients in the 6 months following transplantation.

The International Society for Heart and Lung Transplantion (ISHLT) Guidelines for the Care of Heart Transplant Recipients were originally published in 2010.635Costanzo MR Dipchand A Starling R et al.The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients.J Heart Lung Transplant. 2010; 29: 914-956Google Scholar 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 perioperative 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 CriteriaTabled 1Class IEvidence and/or general agreement that a given treatment or procedure is beneficial, useful, and effectiveClass IIConflicting evidence and/or divergence of opinion about the usefulness/efficacy of the treatment or procedureClass IIaWeight of evidence/opinion is in favor of usefulness/efficacyClass IIbUsefulness/efficacy is less well established by evidence/opinionClass IIIEvidence or general agreement that the treatment or procedure is not useful or effective and in some cases may be harmfulLevel of evidence AData derived from multiple randomized clinical trials or meta-analysesLevel of evidence BData derived from a single randomized clinical trial or large non-randomized studiesLevel of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registries Open table in a new tab Chair: Kumud Dhital Co-Chair: Estela Azeka Contributing Writers: Monica Colvin, Eugene DePasquale, Marta Farrero, Luis García-Guereta, Gina Jamero, Kiran Khush, Jacob Lavee, CJ Michaud, Jignesh Patel, Stephanie Pouch There is an important interplay between frailty and heart failure (HF). Frailty is an independent predictor for the development of HF.1Khan H Kalogeropoulos AP Georgiopoulou VV et al.Frailty and risk for heart failure in older adults: the health, aging, and body composition study.Am Heart J. 2013; 166: 887-894Google Scholar 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).2Moayedi Y Duero Posada JG Foroutan F et al.The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure.Clin Transplant. 2018; 32: e13158Google ScholarA 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.3Jha SR Hannu MK Chang S et al.The prevalence and prognostic significance of frailty in patients with advanced heart failure referred for heart transplantation.Transplantation. 2016; 100: 429-436Google Scholar 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.3Jha SR Hannu MK Chang S et al.The prevalence and prognostic significance of frailty in patients with advanced heart failure referred for heart transplantation.Transplantation. 2016; 100: 429-436Google Scholar, 4Chung CJ Wu C Jones M et al.Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement.J Card Fail. 2014; 20: 310-315Google Scholar, 5Macdonald PS Gorrie N Brennan X et al.The impact of frailty on mortality after heart transplantation.J Heart Lung Transplant. 2021; 40: 87-94Google Scholar Prevalence of malnutrition in the heart failure population is high and represents an independent predictor of poor outcome and mortality.6Aggarwal A Kumar A Gregory MP et al.Nutrition assessment in advanced heart failure patients evaluated for ventricular assist devices or cardiac transplantation.Nutr Clin Pract. 2013; 28: 112-119Google Scholar 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 5.7Russo MJ Hong KN Davies RR et al.The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?.Ann Surg. 2010; 251: 144-152Google Scholar 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.6Aggarwal A Kumar A Gregory MP et al.Nutrition assessment in advanced heart failure patients evaluated for ventricular assist devices or cardiac transplantation.Nutr Clin Pract. 2013; 28: 112-119Google Scholar,8Barge-Caballero E García-López F Marzoa-Rivas R et al.Prognostic value of the nutritional risk index in heart transplant recipients.Revis Española Cardio (English Edition). 2017; 70: 639-645Google Scholar,9Lin H Zhang H Lin Z Li X Kong X Sun G. Review of nutritional screening and assessment tools and clinical outcomes in heart failure.Heart Fail Rev. 2016; 21: 549-565Google Scholar 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.9Lin H Zhang H Lin Z Li X Kong X Sun G. Review of nutritional screening and assessment tools and clinical outcomes in heart failure.Heart Fail Rev. 2016; 21: 549-565Google Scholar Preliminary studies regarding prehabilitation, exercise, and nutrition interventions before surgery have shown promising results with improved outcomes postsurgery.10West MA Wischmeyer PE Grocott MPW. Prehabilitation and nutritional support to improve perioperative outcomes.Curr Anesthesiol Rep. 2017; 7: 340-349Google Scholar 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.7Russo MJ Hong KN Davies RR et al.The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?.Ann Surg. 2010; 251: 144-152Google Scholar 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.11Kulak CA Borba VZ Kulak Jr., J Custodio MR Osteoporosis after transplantation.Curr Osteoporos Rep. 2012; 10: 48-55Google Scholar,12Rahman A Jafry S Jeejeebhoy K Nagpal AD Pisani B Agarwala R. Malnutrition and cachexia in heart failure.J Parenter Enteral Nutr. 2016; 40: 475-486Google Scholar Cardiac rehabilitation has been shown to improve functional capacity and decrease hospital readmissions in HF patients, and is currently recommended by guidelines.13Piepoli MF Conraads V Corra U et al.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.Eur J Heart Fail. 2011; 13: 347-357Google Scholar,14Ponikowski P Voors AA Anker SD et al.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.Eur Heart J. 2016; 37: 2129-2200Google Scholar Prehabilitation has been shown to decrease post-operative complication after cardiovascular or abdominal surgery.15Barberan-Garcia A Ubre M Roca J et al.Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery: a randomized blinded controlled trial.Ann Surg. 2018; 267: 50-56Google Scholar,16Drudi LM Tat J Ades M et al.Preoperative exercise rehabilitation in cardiac and vascular interventions.J Surg Res. 2019; 237: 3-11Google Scholar Physical activity was related to increased event-free survival on the HT waiting list17Spaderna H Vogele C Barten MJ Smits JMA Bunyamin V Weidner G. Physical activity and depression predict event-free survival in heart transplant candidates.Health Psychol. 2014; 33: 1328-1336Google Scholar and better functional capacity and health-related quality of life in heart failure, heart transplant, or left ventricular assist device (LVAD) patients.18Karapolat H Engin C Eroglu M et al.Efficacy of the cardiac rehabilitation program in patients with end-stage heart failure, heart transplant patients, and left ventricular assist device recipients.Transplant Proc. 2013; 45: 3381-3385Google Scholar 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, before transplant, to optimize factors that are modifiable, based on pretransplant 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.19Dew MA DiMartini AF Dobbels F et al.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.J Heart Lung Transplant. 2018; 37: 803-823Google Scholar The presence of pretransplant 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 pretransplant PH is associated with significantly worse short-term survival post HT compared to patients without pretransplant PH.20Crawford TC Leary PJ Fraser CD et al.Impact of the new pulmonary hypertension definition on heart transplant outcomes.Chest. 2020; 157: 151-161Google Scholar,21Yost G Gregory M Bhat G Short-form nutrition assessment in patients with advanced heart failure evaluated for ventricular assist device placement or cardiac transplantation.Nutr Clin Pract. 2014; 29: 686-691Google Scholar 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.22Tedford RJ Beaty CA Mathai SC et al.Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.J Heart Lung Transplant. 2014; 33: 289-297Google Scholar First, PH is defined by a mean PAP (mPAP) greater than 20 mm Hg (previously greater than 25 mm Hg). The lower parameter reflects recent studies suggesting that individuals with mPAP 21 to 24 mm Hg 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(20 mm Hg or less).23Condon DF Nickel NP Anderson R Mirza S de Jesus Perez VA The 6th world symposium on pulmonary hypertension: what's old is new.F1000Research. 2019; 8: 888Google Scholar,24Tsukashita M Takayama H Takeda K et al.Effect of pulmonary vascular resistance before left ventricular assist device implantation on short- and long-term post-transplant survival.J Thorac Cardiovasc Surg. 2015; 150 (e2): 1352-1361Google Scholar 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.22Tedford RJ Beaty CA Mathai SC et al.Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.J Heart Lung Transplant. 2014; 33: 289-297Google Scholar,25Vakil K Duval S Sharma A et al.Impact of pre-transplant pulmonary hypertension on survival after heart transplantation: a UNOS registry analysis.Int J Cardiol. 2014; 176: 595-599Google ScholarTable 1Hemodynamic Profiles of Pulmonary HypertensionaThe 6th World Symposium on Pulmonary Hypertension defined three hemodynamic profiles of pulmonary hypertension (PH): isolated precapillary PH, combined. The pre- and postcapillary PH, and isolated postcapillary PH).22ClassificationMean pulmonary artery pressurePulmonary capillary wedge pressurePulmonary vascular resistanceIsolated pre-capillary PH>20 mm Hg<15 mm Hg>3 WUCombined pre- and post-capillary PH>15 mm Hg>3 WUIsolated post-capillary PH>15 mm Hg<3 WUWU, wood units.a The 6th World Symposium on Pulmonary Hypertension defined three hemodynamic profiles of pulmonary hypertension (PH): isolated precapillary PH, combined. The pre- and postcapillary PH, and isolated postcapillary PH).22Tedford RJ Beaty CA Mathai SC et al.Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension.J Heart Lung Transplant. 2014; 33: 289-297Google Scholar Open table in a new tab WU, wood units. Right heart catheterization should be performed on all adult candidates in preparation for listing, and periodically when patients are listed.26Mehra MR Canter CE Hannan MM et al.The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: a 10-year update.J Heart Lung Transplant. 2016; 35: 1-23Google Scholar 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. 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 preclinical 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.27Koulova 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.J Thorac Dis. 2017; 9: 2640-2649Google Scholar 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 mechanical circulatory support (MCS). MCS therapy should be directed by the trajectory of HF progression and clinical status.28den Uil CA Akin S Jewbali LS et al.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.Eur J Cardiothorac Surg. 2017; 52: 14-25Google Scholar, 29Feldman D Pamboukian SV Teuteberg JJ et al.The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: executive summary.J Heart Lung Transplant. 2013; 32: 157-187Google Scholar, 30Nagpal 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.Can J Cardiol. 2017; 33: 110-118Google Scholar, 31Peura JL Colvin-Adams M Francis GS et al.Recommendations for the use of mechanical circulatory support: device strategies and patient selection: a scientific statement from the American Heart Association.Circulation. 2012; 126: 2648-2667Google Scholar, 32Potapov EV Antonides C Crespo-Leiro MG et al.2019 EACTS expert consensus on long-term mechanical circulatory support.Eur J Cardiothorac Surg. 2019; 56: 230-270Google Scholar, 33Rihal CS Naidu SS Givertz MM et al.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.J Am Coll Cardiol. 2015; 65: e7-e26Google Scholar, 34Sánchez-Enrique C Jorde UP González-Costello J Heart transplant and mechanical circulatory support in patients with advanced heart failure.Rev Española Cardiol (English Edition). 2017; 70: 371-381Google Scholar 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.35Chen CK Manlhiot C Mital S et al.Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.Pediatr Transplant. 2018; 22: e13105Google Scholar,36Peng D Schumacher K. Risk factors for early and late mortality in pediatric heart transplantation.Pediatr Heart Transplant. 2019; : 224-248Google Scholar Pediatric risk factor models have been studied in early and late mortality.35Chen CK Manlhiot C Mital S et al.Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis.Pediatr Transplant. 2018; 22: e13105Google Scholar Risk factors for early mortality include: recipient variables such as diagnosis, age, gender, sensitization, pulmonary vascular resistance, noncardiac 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 0.81.37Almond 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.Am J Transplant. 2012; 12: 1240-1248Google Scholar The risk factor model using donor variables on 1-year or late mortality post-transplant has been studied using the OPTN registry38Zafar F Jaquiss RD Almond CS et al.Pediatric Heart Donor Assessment Tool (PH-DAT): a novel donor risk scoring system to predict 1-year mortality in pediatric heart transplantation.J Heart Lung Transplant. 2018; 37: 332-339Google Scholar 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 status in most pediatric chronic conditions is a major determinant of childhood well-being. Chronic HF in children is a major cause of malnutrition.39Godown J Friedland-Little JM Gajarski RJ et al.Abnormal nutrition affects waitlist mortality in infants awaiting heart transplant.J Heart Lung Transplant. 2014; 33: 235-240Google Scholar, 40Heuschkel RB Gottrand F Devarajan K et al.ESPGHAN position paper on management of percutaneous endoscopic gastrostomy in children and adolescents.J Pediatr Gastroenterol Nutr. 2015; 60: 131-141Google Scholar, 41Kirk R Dipchand AI Rosenthal DN et al.The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: executive summary.J Heart Lung Transplant. 2014; 33: 888-909Google Scholar, 42Schwarz SM Gewitz MH See CC et al.Enteral nutrition in infants with congenital heart disease and growth failure.Pediatrics. 1990; 86: 368-373Google Scholar, 43Spillane NT Kashyap S Bateman D Weindler M Krishnamurthy G. Comparison of feeding strategies for infants with hypoplastic left heart syndrome: a randomized controlled trial.World J Pediatr Congenital Heart Surg. 2016; 7: 446-453Google Scholar 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, proinflammatory cytokines, neurohormonal abnormalities, increased metabolic demands, reduced intake, and malabsorption.44Lewis KD Conway J Cunningham C Larsen BMK. Optimizing nutrition in pediatric heart failure: the crisis is over and now it's time to feed.Nutr Clin Pract. 2018; 33: 397-403Google Scholar 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 curves44Lewis KD Conway J Cunningham C Larsen BMK. Optimizing nutrition in pediatric heart failure: the crisis is over and now it's time to feed.Nutr Clin Pract. 2018; 33: 397-403Google Scholar,45WHO Child Growth Standards. Available at: https://wwwwhoint/childgrowth/standards/en/. 2021.Google Scholar (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

Purpose Hypertension (HTN) is common in heart transplant (HTx) recipients due to calcineurin inhibitors, steroids and renal disease. HTN increases risk of transplant vasculopathy, left ventricular hypertrophy, and renal failure, emphasizing need for adequate control. We assessed the effectiveness of nurse practitioner (NP) telehealth visits in achieving adequate blood pressure (BP) control in HTx patients (pts). Methods A retrospective study included HTx pts scheduled for a video or telephone visit with a HTx NP for BP management between Sept 2020 and July 2021. Pts hypertensive during a clinic visit, and requiring initiation or adjustment of antihypertensives, were referred for a follow up NP telehealth visit. Target BP goal was <130/80. Pts were instructed to obtain sitting BP 1-2 times/day at home, 2 hours after taking BP medications. Data obtained: BP measurements at clinic and with each NP telehealth visit, number of days from intervention to attainment of goal BP, number of NP visits conducted, and number of antihypertensive agents required to reach goal BP. Results Of 73 pts, 60 were followed by NP until target BP reached, 13 pts were hospitalized, lost to follow up, transferred care locally, or still undergoing titration of antihypertensives by NP. Of the 60 pts, average number of days to attain goal BP was 40.7 days, 83% of pts required 1-2 NP telehealth visits to attain goal BP, 78% of pts required 1-2 antihypertensive agents to attain goal BP. Conclusion NP telehealth BP management was effective in achieving target BP efficiently in HTx pts. Further studies evaluating long term BP control and optimal frequency of visits should be conducted.

Purpose Diversity in the United States is a point of keen interest within the communities. In the heart transplant selection committees, most programs believe they have no bias in accepting patients for heart transplantation. However, there may be some inherent biases that are not due to the program's decisions, but rather institutional decisions or limitations. Such limitations may include lack of medical insurance, gender, age or geography that may be present without foreknowledge. Therefore, we assessed our heart transplant selection committee decisions to assess whether there is any inherent, institutional or voluntary bias within committee decisions. Methods Between 2016 and 2020 we assessed 296 heart transplant candidates that were presented to the heart transplant selection committee. We assessed for various factors that may be associated with patients declined for transplant for age, gender, race, social support (SIPAT score), health insurance (Medicaid), and state of residence. The standard for comparison included a Caucasian with non-Medicaid health insurance, social support, and ability to travel. Results The declined patients compared to the accepted patients were significantly older (64.4 vs 54.6 years) and had a higher SIPAT score (13.7 vs 11.2). There was no difference between groups in % female, % non-Caucasian, % w/non-Medicaid health insurance and % from outside California. (see table) Conclusion Inherent bias within a selection committee is difficult to interpret as older patients are held to a higher standard as older age is a risk factor for lower post-transplant survival. Higher SIPAT scores are also known to be a risk for lower survival due to higher psychosocial risk. It is comforting to appreciate that there does not appear to be inherent bias in gender, race, type of health insurance and region. Larger studies are needed.

Purpose Donor selection in heart transplant is not standardized. Many donor hearts (DH) are declined due to quality issues such as older age, low left ventricular ejection fraction, left ventricular hypertrophy, diastolic dysfunction, underlying coronary artery disease. Yet, DH declined at one center are subsequently accepted at another center. It is not well known whether DHs declined due to quality and accepted by another program have acceptable post-transplant outcomes. Methods Between 2017 and 2019, we assessed 532 DHs that were allocated to a single center at Cedars-Sinai (CS). We declined 218 offers due to poor quality. We had follow-up with organ procurement organizations and found that 45 of these DHs that we turned down for poor quality were accepted by another program and transplanted. 1-year post-transplant survival of these patients were compared to those patients whose donor was accepted and transplanted at CS (n=314). Results The 45 declined DHs had the following issues: abnormal cardiac studies (n=12), donor cardiac history (n=6), other medical history including cirrhosis or infectious processes (n=6), possible cardiac cause of death (n=3), older age (n=14), estimated prolonged ischemic time (n=1), and other reasons (n=3). Compared to those patients transplanted at CS, there was no difference in 1-year patient or graft survival. The declined donor patients compared to CS patients had similar age and gender but had a longer cold ischemic time and less patients listed as high urgency status (status 1-3) at transplant. (see table). Conclusion DHs declined for quality may be accepted at another program with good post-transplant survival. Contrary to belief, these DHs were mostly not transplanted into high urgency waitlist patients. Donor declines due to quality should be reviewed as they could lead to more lives saved.

Purpose Heart-liver transplant (HLvTx) has been demonstrated to show an immune protective effect with the transplanted liver protecting the heart. There are several reports suggesting less rejection in the HLvTx group. It has not been established whether this benefit is present in the current era. Methods Between 2007 and 2017, we assessed 13 HLvTx patients compared to heart alone patients (HATx, n=758). Patients were assessed for freedom from 1-year rejection [acute cellular rejection (ACR) and antibody-mediated rejection (AMR)] and donor-specific antibodies (DSA). Other endpoints included 5-year survival and freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography) and non-fatal major adverse cardiac event (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke). Results HLvTx compared to HATx showed similar freedom from 1-year rejection (ACR, AMR) and DSA. 5-year survival, freedom from CAV and NF-MACE were also similar between the two groups (see table). Conclusion In the current era, HLvTx does not appear to provide immune protection in either rejection or CAV. A larger number of heart-liver transplant patients will be needed to confirm these findings.