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

ChairCostanzo MR: Midwest Heart Foundation, Lombard Illinois, USATask Force 1Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesù, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UKTask Force 2Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria.Task Force 3Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruña, La Coruña, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USAIndependent ReviewersDelgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium. Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesù, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruña, La Coruña, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium. Since the dawn of heart transplantation in the 1960s, the medical care of heart transplant recipients has been guided by the experience of individual clinicians and has varied from center to center. Despite many advances in surgical techniques, diagnostic approaches, and immunosuppressive strategies, survival after heart transplantation is limited by the development of cardiac allograft vasculopathy and by the adverse effects of immunosuppression. The International Society for Heart and Lung Transplantation (ISHLT) has made an unprecedented commitment to convene experts in all areas of heart transplantation to develop practice guidelines for the care of heart transplant recipients. After a vast effort involving 40 writers from 9 countries worldwide, the ISHLT Guidelines for the Care of Heart Transplant Recipients have now been completed and the Executive Summary of these guidelines is the subject of this article. The document results from the work of 3 Task Force groups:•Task Force 1 addresses the peri-operative care of heart transplant recipients, including the surgical issues affecting early post-operative care; monitoring and treatment of early hemodynamic, metabolic, and infectious issues; evaluation and treatment of allosensitization; evaluation and treatment of early coagulopathies; the organization of a multidisciplinary care team; management of ABO “incompatible” pediatric heart transplantation; and the use of extracorporeal membrane oxygenation (ECMO) for the hemodynamic support of pediatric recipients.•Task Force 2 discusses the mechanisms, diagnosis, and treatment of heart transplant rejection; the mechanisms of action, dosing, and drug level monitoring of immunosuppressive drugs as well as their adverse effects and interactions with concomitantly used medications; and reviews the major clinical trials and the immunosuppressive strategies to be used in special clinical situations.•Task Force 3 covers the myriad of clinical issues occurring long-term after heart transplantation, including cardiac allograft vasculopathy, the chronic adverse effects of immunosuppression (neurotoxicity, renal insufficiency, hypertension, bone disease, diabetes and malignancy), as well as reproductive health, exercise, psychologic problems, return to work, and operation of motor vehicles after heart transplantation. It is important to note that each task force was co-chaired by a pediatric heart transplant physician who had the specific mandate to highlight issues unique to the pediatric heart transplant population and to ensure their adequate representation. As the reader will undoubtedly observe, most of the recommendations only achieve a Level of Evidence C, indicating that these recommendations are based on expert consensus and not on randomized controlled clinical trials. A concerted effort was also made to highlight the numerous gaps in evidence pertaining to many aspects of the care of heart transplant recipients. This lack of “evidence-based” recommendations is mostly due to the limited number of heart transplant recipients worldwide. However, it is the hope of all contributing writers and reviewers that the increased awareness of the “gaps in evidence” provided by these guidelines will spur further research in many important areas of heart transplantation. Chair: Maria Rosa Costanzo, MD; Co-Chairs: Anne Dipchand, MD; Randall Starling, MD Contributing Writers: Allen Anderson, MD; Michael Chan, MD; Shashank Desai, MD; Savitri Fedson, MD; Patrick Fisher, MD; Gonzalo Gonzales-Stawinski, MD; Luigi Martinelli, MD; David McGiffin, MD; Jon Smith, MD 1Taking into consideration only the variable of “donor age,” the hearts of donors younger than 45 years will invariably have sufficient reserves to withstand the rigors of heart transplant (HT) even in settings of prolonged ischemic time, recipient comorbidities, and multiple previous recipient operations with hemodynamically destabilizing bleeding. Hearts from donors between the ages of 45 and 55 years should probably be used when the projected ischemic time is ≤ 4 hours and the potential recipient does not have comorbidities or surgical issues where anything less than robust donor heart performance could prove fatal. The use of donor hearts > 55 years should only be used if the survival benefit of HT for a recipient unequivocally exceeds the decrement in early HT survival due to transplantation of a heart with limited myocardial reserves.Level of Evidence: B. 1Hearts from donors with severe infection can be used provided that (1) the donor infection is community acquired and donor death occurs rapidly (within 96 hours); (2) repeat blood cultures before organ procurement are negative; (3) pathogen-specific anti-microbial therapy is administered to the donor; (4) donor myocardial function is normal; and (5) there is no evidence of endocarditis by direct inspection of the donor heart. If such hearts are used for transplantation, the recipient should undergo surveillance blood cultures on the first post-operative day and pathogen-specific anti-biotic therapy should be administered for an appropriate duration of time.Level of Evidence: C. 1Hearts from donors with a history of past or current non-intravenous (IV) cocaine abuse can be used for transplantation provided cardiac function is normal and LVH is absent.Level of Evidence: C.2In light of current information, the use of hearts from donors with a history of “alcohol abuse” remains uncertain, but is should probably be considered unwise.Level of Evidence: C.3The use of hearts from donors who have died of carbon monoxide intoxication can be recommended with caution, although the safety has not been completely established. It is recommended that these hearts be used provided there is a normal donor electrocardiogram (ECG) and echocardiogram, minimal elevation of cardiac markers, minimal inotropic requirements, a relatively short ischemic time, a favorable donor to recipient weight ratio and a recipient with normal pulmonary vascular resistance.Level of Evidence: C. 1As far as the function is concerned, a donor heart should not be used in the presence of intractable ventricular arrhythmias, the need for excessive inotropic support (dopamine at a dose of 20 μg/kg/min or similar doses of other adrenergic agents despite aggressive optimization of pre-load and after-load), discreet wall motion abnormalities on echocardiography or left ventricular ejection fraction (LVEF) < 40% despite optimization of hemodynamics with inotropic support.Level of Evidence: B.2A donor heart with a normally functioning bicuspid aortic valve can be used for HT. Anatomically and hemodynamically abnormal aortic and mitral valves may undergo bench repair or replacement with subsequent transplantation of the heart.Level of Evidence: C. 1The use of donor hearts with obstructive disease in any major coronary artery should be avoided unless the heart is being considered for the alternate list recipients with concomitant coronary bypass surgery.Level of Evidence: C.2It would seem appropriate to use hearts from donors with left ventricular hypertrophy (LVH) provided it is not associated with ECG findings of LVH and LV wall thickness is < 14 mm.Level of Evidence: C. 1As far as the function is concerned, a donor heart should not be used in the presence of intractable ventricular arrhythmias, the need for excessive inotropic support (dopamine at a dose of 20 mcg/kg/min or similar doses of other adrenergic agents despite aggressive optimization of preload and after load), discreet wall motion abnormalities on echocardiography or LV ejection fraction < 40% despite optimization of hemodynamics with inotropic support.Level of Evidence: B. 1As a general rule, the use of hearts from donors whose body weight is no greater than 30% below that of the recipient is uniformly safe. Furthermore, a male donor of average weight (70 kg) can be safely used for any size recipient irrespective of weight. Use of a female donor whose weight is more than 20% lower than that of a male recipient should be viewed with caution.Level of Evidence: C. 1As a general rule the ischemic time should be less than 4 hours. However, there are situations in which ischemic times longer than 4 hours are anticipated. Donor hearts with ischemic times longer than 4 hours should only be accepted when other factors interacting with ischemic time are ideal, including donor young age, normal cardiac function, and absence of inotropic support.Level of Evidence: C. 1Peri-operative monitoring of heart transplant recipients should include (1) continuous ECG monitoring; (2) post-operative 12-lead ECG; (3) invasive arterial pressure monitoring; (4) direct measurement of right atrial pressure (RAP) or central venous pressure (CVP); (5) measurement of left atrial or pulmonary artery wedge pressure (PAWP); (6) intermittent measurement of cardiac output (CO); (7) continuous measurement of arterial oxygen saturation; (8) intraoperative transesophageal echocardiogram (TEE); (9) continuous assessment of urinary output.Level of Evidence: C. 1Tricuspid valve regurgitation identified intraoperatively and estimated to be moderate or severe (> 2+), should be re-evaluated by transthoracic echocardiogram (TTE) or TEE within 24 hours of HT and closely monitored for the first few post-operative days. The frequency of subsequent follow-up should be guided by clinical and hemodynamic variables.Level of Evidence: C. 1DeVega annuloplasty of the donor tricuspid valve (TV) can be considered to maintain the normal size of the TV annulus.Level of Evidence: C. 1Pericardial effusions occurring after HT should be monitored by echocardiogram.2Percutaneous or surgical drainage should be done when the pericardial effusion causes hemodynamic compromise.Level of Evidence: C. 1Pericardial effusions that are not hemodynamically compromising do not require drainage unless there is a strong suspicion of an infectious etiology.Level of Evidence: C. (See Table 1)Table 1Properties of Intravenous Vasoactive Drugs Used after Heart TransplantationAdapted and reprinted with permission from Kirklin JK, et al.46Kirklin J.K. Young J.B. McGiffin D.C. Heart transplantation. Churchill Livingstone, Philadelphia2002Google ScholarPeripheral vasoconstrictionCardiac contractilityPeripheral vasodilationChronotropic effectArrhythmia riskIsoproterenol0+++++++++++++++Dobutamine0+++++++Dopamine++++++++Epinephrine+++++++++++++Milrinone/enoximone0++++++++Norepinephrine+++++++0++Phenylephrine++++0000Vasopressin++++0000 Open table in a new tab 1Continuous infusion of an inotropic agent should be used to maintain hemodynamic stability post-operatively. Inotropic agents should be weaned as tolerated over the first 3 to 5 days. The lowest effective dose should be used.Level of Evidence: C.2The following therapies are suggested:aisoproterenol, 1 to 10 μg/min, orbdobutamine, 1 to 10 μg/kg/min ± dopamine 1 to 10 μg/kg/min, orcisoproterenol, 1 to 10 μg/min ± dopamine 1 to 10 μg/kg/min, ordmilrinone, 0.375 to 0.75 μg/kg/minLevel of Evidence: C.3Continuous infusion of α-adrenergic agonists including phenylephrine, norepinephrine, or epinephrine can be used to maintain adequate mean arterial pressure.Level of Evidence: C.4Low dose vasopressin (0.03–0.1 U/min) or methylene blue can be added to α-agonist for vasodilatory shock.Level of Evidence: B. (See Figure 1) 1Inotropic agents that can be used to augment right ventricle (RV) function include isoproterenol, milrinone, enoximone, dobutamine, and epinephrine.Level of Evidence: C. 1Systemic vasodilators with pulmonary vasodilating properties, including nitroglycerine and sodium nitroprusside, can be used in the absence of systemic hypotension.Level of Evidence: C.2Selective pulmonary vasodilators that can be used in the management of peri-operative RV dysfunction include (1) prostaglandins (prostaglandin E1 [alprostadil], prostaglandin I2 [epoprostenol or prostacyclin], inhaled iloprost); (2) inhaled nitric oxide; (3) sildenafil.Level of Evidence: C. 1Mechanical circulatory support (MCS) should be initiated early if there is failure to wean from cardiopulmonary bypass (CPB) or other evidence of heart allograft failure such as the requirement for multiple high-dose inotropic agents to permit separation from CPB.Level of Evidence: B.2MCS should be considered if there is continued or worsening hemodynamic instability, such as decreasing cardiac index (CI) and a falling MVO2 or MVO2 < 50% that is not corrected by appropriate resuscitation.Level of Evidence: B.3Support for either LV or RV failure should escalate from pharmacotherapy to IABP to MCS.Level of Evidence: B.4Small ventricular assist devices (VADs) such as the TandemHeart and Levitronix Centrimag can provide adequate support for RV, LV, or biventricular (BiV) failure, and have benefits of ease of implantation, management, and explant.Level of Evidence: C. 1In the presence of hemodynamic instability, cardiac tamponade should be excluded by direct surgical exploration. The presence of hyperacute/antibody-mediated rejection should also be excluded. If hemodynamic instability persists in the absence of cardiac tamponade, MCS should be considered.Level of Evidence: C.2The timing MCS discontinuation should be guided by evidence of graft recovery. If there is no evidence of graft functional recovery within 3 to 4 days, hyperacute and antibody-mediated rejection should be excluded and the option of listing for repeat HT may be considered.Level of Evidence: C. 1Use of ECMO support in adults requires consideration of the risk of infection, immobility, and need for anti-coagulation.Level of Evidence: C. 1The increased risk of post-operative RV dysfunction must be carefully evaluated in children, although evidence suggests that children can safely undergo HT despite elevation of pulmonary vascular resistance (PVR) above values considered unsafe in adults.Level of Evidence: C.2Contrary to the experience and practice in adults, the first choice for support in the setting of primary graft failure (PGF) in the pediatric setting should be ECMO. Level of Evidence C. 1Pharmacologic chronotropic agents, including isoproterenol and theophylline can be used in the peri-operative setting to increase heart rate.Level of Evidence: B.2Atrial and ventricular temporary epicardial pacing wires should be placed at the time of HT even if the initial rhythm is sinus.Level of Evidence: B.3After HT, temporary pacing should be initiated in the setting of relative bradycardia to maintain heart rates of > 90 beats/min.Level of Evidence: B.4Pacing guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) and the European Society of Cardiology (ESC) lack recommendations specific for temporary pacing early after HT. Recommendations for permanent pacing exist for inappropriate chronotropic response 3 weeks after HT. Standard atrium-paced, atrium-sensed, inhibited-rate modulation (AAIR) or dual-paced, dual-sensed, dual-response to sensing, rate modulation (DDDR) pacemakers are preferable.Level of Evidence: C.5Treatment of tachyarrhythmias should be aimed at rate control.Level of Evidence: B.6Persistent tachyarrhythmias, whether atrial or ventricular, should prompt investigation of possible rejection and electrophysiological evaluation if rejection is absent.Level of Evidence: B.7Sustained ventricular tachycardia (SVT) should be evaluated with both an angiogram and an endomyocardial biopsy (EMB).Level of Evidence: B. 1The Class III anti-arrhythmics sotalol and amiodarone can be safely used in HT recipients and have minimal interaction with immunosuppressive agents.Level of Evidence: C.2Non-dihydropyridine calcium channel blockers (CCBs) and β-blockers may be used in HT recipients for rate control.Level of Evidence: B. 1The CVP should be maintained between 5 and 12 mm Hg, a level that provides adequate cardiac filling pressures without causing RV overload.Level of Evidence: C.2Colloid replacement is generally preferred in the first 24 hours after HT; blood, if indicated, is the first choice.Level Evidence: C.3Compatible blood products may be safely administered after HT without increasing the risk for rejection. In the setting of ABO incompatible pediatric HT special care must be taken in the selection of compatible products to account for both donor and recipient blood types.Level of Evidence: B.4Blood products should be leukocyte-depleted. Blood products should be cytomegalovirus (CMV) negative if donor and recipient are CMV negative.Level of Evidence: B.5IV loop diuretics are used to decrease volume overload. In addition to intermittent IV bolus, continuous IV infusion of loop diuretics with or without sequential nephronal blockade using thiazide diuretics or aldosterone antagonists may be necessary.Level of Evidence: C.6Hemodialysis for renal failure should be initiated early for both volume management and renal replacement. If the recipient is anuric, oliguric, or has a sharp rise in sCr within 2 to 4 hours after HT, then hemodialysis may be necessary.Level of Evidence: B. 1Ultrafiltration should be considered if RAP remains elevated (> 20 mm Hg) despite pharmacologic interventions.Level of Evidence: B. 1Delay of initiation of calcineurin inhibitor (CNI) therapy should be considered if there is significant pre-operative renal insufficiency or deterioration of kidney function in the first 2 post-operative days.Level of Evidence: C. 1Oral hypoglycemic agents should be discontinued pre-operatively.Level Evidence: C. 1A continuous infusion insulin regimen should be used to maintain blood glucose below 200 mg/dL during the intensive care unit (ICU) stay.Level of Evidence: B.2Aggressive management of hyperglycemia should be continued for the duration of hospitalization.Level of Evidence: C. 1Pre-operative anti-biotic prophylaxis should be used before the transplant operation.Level of Evidence: B.2Drugs should be selected based upon their activity against usual skin flora, specifically Staphylococcus species.Level of Evidence: B.3If a chronically infected device such as a VAD or a pacemaker is present, then peri-operative anti-biotics should be selected based on microbiologic sensitivities.Level of Evidence: B.4In the event that the donor had an ongoing bacterial infection, a course of suitable anti-biotics should be considered.Level of Evidence: B. (See Table 2)Table 2Typical Recommendations for the Prevention of Cytomegalovirus in Heart Transplant RecipientsGroupRecommendations/OptionsD+/R–Oral ganciclovir (1000 g PO TID) or valganciclovir (900 mg PO/day) for 3 monthsorIV ganciclovir (5–10 mg/kg/day) for 1–3 monthsPreemptive therapy generally not preferred due to high risk of diseaseSome HT centers will add CMV immune globulin for high risk patientsR+Oral ganciclovir (1000 g PO TID) or valganciclovir (900 mg PO/day) for 3 monthsorIV ganciclovir (5–10 mg/kg/day) for 1–3 monthsorPreemptive therapy. Monitor with nucleic acid testing or CMV antigenemia assayTherapy with IV ganciclovir or oral valganciclovirCMV, cytomegalovirus; D, donor; HT, heart transplant; IV, intravenous; PO, oral (per os); R, recipient; TID, 3 times daily. Open table in a new tab CMV, cytomegalovirus; D, donor; HT, heart transplant; IV, intravenous; PO, oral (per os); R, recipient; TID, 3 times daily. 1Prophylaxis against CMV should be initiated within 24 to 48 hours after HT.Level of Evidence: A.2The CMV serologic status of the donor and recipient may be used to stratify the patient as low-risk, intermediate-risk, or high-risk for developing a CMV infection.Level of Evidence: A.3Intravenous ganciclovir may be administered to intermediate and high-risk patients, whereas patients at low-risk for CMV infection may only receive anti-herpes simplex virus prophylaxis with acyclovir. (See Table 3.)Table 3Examples of Desensitization TherapiesAdapted from Kobashigawa J, et al.80Kobashigawa J. Mehra M. West L. et al.Report from a consensus conference on the sensitized patient awaiting heart transplantation.J Heart Lung Transplant. 2009; 28: 213-225Abstract Full Text Full Text PDF PubMed Scopus (56) Google ScholarTherapyDoseFrequencyPlasmapheresis(A, F) 1.5 volume exchanges(A) 5 consecutive days(B) 5 times, every other day(C) 2–3 times/week until transplant(D) 5 times, every other day, every 2–4 weeksIntravenous immunoglobulin (IV Ig)(A, B) 2g/kg IV divided over 2 days(A) Every 2–4 weeks(C) 2–3 g/kg IV divided over 4 days(D) 0.1 mg/kg IV(D) Every 2–4 weeks(E) 100 mg/kg IV(E) Every 4 weeks(F) 20 g (of 10% IV Ig)(G) 150 g (of 10% IV Ig) divided over 3 rounds(G) Every 4 weeksRituximab(A) 1 g IV(A) Weekly × 4(C, E) 375 mg/m2(C) ×2 doses(G) 500 mg(E) Weekly × 4(G) Every 2 weeksCyclophosphamide (used in the past)(A) 1 mg/kg orally(A) Daily(C) 0.5 μg/m2(D) 1 mg/kg orally(A) UCLA; (B) Stanford University; (C) University of Maryland; (D) University of Toronto; (E) University of Wisconsin; (F) Loyola University Chicago; (G) University of Berlin. Open table in a new tab Level of Evidence: A. (A) UCLA; (B) Stanford University; (C) University of Maryland; (D) University of Toronto; (E) University of Wisconsin; (F) Loyola University Chicago; (G) University of Berlin. 1Anti-fungal prophylaxis to prevent mucocutaneous candidiasis should be initiated once the recipient is extubated. The agents most commonly used are nystatin (4–6 mL [400,000 to 600,000 units] 4 times daily, swish and swallow) or clotrimazole lozenges (10 mg).Level of Evidence: C. 1Prophylaxis against Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia and Toxoplasma gondii (in indicated cases) should also be initiated in the early post-operative period. Trimethoprim/sulfamethoxazole (80 mg TMP/160 mg SMZ, 1 single- or double-strength tablet per day) is the most commonly used medication. In the setting of a sulfa allergy or glucose-6-phosphate dehydrogenase deficiency, alternative regimens can be used, including: (1) Aerosolized pentamidine (AP) isethionate (300 mg every 3–4 weeks). (2) Dapsone (diaminodiphenylsulfone) with or without TMP or pyrimethamine (50–100 mg/day). Pyrimethamine may be administered weekly (25 or 50 mg) to supplement dapsone (50–100 mg/day). Dapsone is metabolized via the hepatic cytochrome P-450 system (CYP3A). (3) Atovaquone (1500 mg PO QD). (4) Clindamycin and pyrimethamine.Level of Evidence: B. 1IV anti-fungal prophylaxis should be considered for infants (< 1 year of age) with an open chest and/or requiring ECMO support in the peri-operative period.Level of Evidence: C.2Prophylaxis for Pneumocystis jiroveci should be instituted for a minimum of 3 months up to a maximum of 24 months after HT.Level of Evidence: C. 1Screening panel reactive antibodies (PRA) should be performed in all HT candidates