Heart Transplantation Helene Logginidou, MD Clinical Assistant Professor Anesthesiology-Critical Care

Heart transplantation has become established treatment option First Heart Transplant in 1967 by Dr Barnard in South Africa. Pt survived 18 days. However, successful transplantation of a human heart was not ready for widespread clinical application until medications were developed to prevent the recipient from "rejecting" the donor heart. This happened in 1983 when the Food and Drug Administration (FDA) approved a drug called cyclosporine (Gengraf, Neoral). For end-stage heart about 2000 heart transplants performed annually in the United States. Survival rates following heart transplantation are about: 87% at 1 year, 70% at 5 years and 50% at 12 years. Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.

Indications for heart transplantation Deteriorating cardiac function and having a prognosis of less than 1 year to live. Dilated cardiomyopathy Ischemic cardiomyopathy Congenital heart disease for which no conventional therapy exists or that conventional therapy has failed Ejection fraction less than 20% Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted Pulmonary vascular resistance of less than 2 Wood units ( 160 dyn.s.cm-5) Age younger than 65 years Ability to comply with medical follow-up care

Contraindications for Heart Transplantation Healthy donor hearts are in short supply, strict rules dictate criteria for heart transplant recipients. Patients who may be too sick to survive the surgery or the side effects of immunosuppressive therapy would not be good transplant candidates. Active infection Pulmonary hypertension Chronic lung disease with loss of more than 40% of lung function Untreatable liver or kidney disease Diabetes that has caused serious damage to vital organs; Disease of the blood vessels in the brain, such as a stroke, Serious disease of the arteries Mental illness or any condition that would make a patient unable to take the necessary medicines on schedule continuing alcohol or drug abuse

- Actual medication and history of intolerance to medication - Surgery report in case of prior cardiac surgery - Heart catheterization data (left- and right-sided pressures, cardiac output, PVR, SVR and coronary angiography) - Evaluation of the present status of the patient: a) Functional class and predominant symptoms/problems b) Physical examination including peripheral/carotid vessels, and oral cavity (dental status) c) ECG d) Chest X-ray e) Blood type and Rhesus factor, electrolytes, renal and liver function, glucose, ESR or CRP, Hb, WBC and differentiation, platelets Serology for HBV and HCV and HIV Urine analysis for protein, glucose and sediment Stool tests for blood loss f) Echocardiogram (dimensions, systolic and diastolic ventricular function, estimation of right-sided pressures, valvular abnormalities) g) Exercise test, preferably with determination of peak VO2 h) Pulmonary function testing Neth Heart J. 2008 March; 16(3): 79–87. N. de Jonge et al. Preoperative Patient Evaluation

Recipient’s Criteria according to UNOS In the United States, the United Network for Organ Sharing (UNOS) determines priority for a heart transplant by grouping patients by the severity of their heart condition. This grouping lets those who need a transplant most be considered first. Status 1A – includes very ill patients who need constant inotropic medicines or mechanical assistance (left ventricular assist devices); these patients are expected to live less than one month without a transplant. Status 1B – includes medically stable patients who need constant inotropic medicines or mechanical assistance (left ventricular assist devices); these patients are expected to live more than one month without a transplant. Status 2 – All patients who do not meet the above standards.

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. Level of Evidence B: At least fair scientific evidence suggests that the benefits of the clinical service outweighs the potential risks. Clinicians should discuss the service with eligible patients. Level of Evidence C: indicating that these recommendations are based on expert consensus and not on randomized controlled clinical trials

Recommendations on Donor Cardiac Function: Class I: 1. 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.

Recommendations on Donor Heart Selection The Journal of Heart and Lung Transplantation, Vol 29, No 8, August 2010 Class IIa: 1. Taking 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 co morbidities, 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 co morbidities 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.

Recommendations on the Use of Donors with Pre-existing Cardiac Abnormalities Class I 1. As 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. 2 A 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. Class Iia 1 The 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. 2 It 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.

Recommendations on Ischemic Times The Journal of Heart and Lung Transplantation, Vol 29, No 8, August 2010 Class I: 1. As a general rule the ischemic time should be less than 4 hours. 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 absence of inotropic support. Level of Evidence: C.

Recommendations on Donor-Recipient Size Matching: Class I: 1. As 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.

Intra Operative Details Surgical technique Excision of Native Heart: Aorta, Pulmonary artery trunk, Cuff of Left Atrium with the four pulmonary venous connections, as well as SVC, and IVC connections remain Bicaval technique Biatrial Technique

Transplant Re-implantation Process: 5 Anastomoses Important the Anatomic Alignment of the Tx Heart in the Chest 1st: Left Atrium: Recipient's native LA Cuff that has remained with the 4 pulmonary veins and the donor’s LA is stitched in a parachute fashion BICAVAL TECHNIQUE: 2nd: IVC-RA ; size matching, tight suturing; no twisting; technically challenging due to the anatomic position and the vessel’s nature 3rd: SVC-RA; again right measurements required to avoid too short or long anastomoses that would result in tension or kinking respectively 4th: Pulmonary Artery anastomosis. The SGC is positioned in the Right PA branch for post op management of the pt 5th: Aorta. Engraftment of Aorta  Restablishment of blood flow ; Tight Seal with the sutures; High Pressures; correct size and alignment required Beating of the New transplanted Heart Starts! Release of Bicaval Snares, aortic cross clamp; Suctioning Catheter in Ascending Aorta remains for Air removal; Gradually wean Pt off Bypass.

View following cardiectomy showing cuffs for bicaval anastomosis.

Perfusion Preservation vs Static A recent development has been the study of Perfusion Preservation★ vs Static✪ preservation of donor hearts for cardiac transplantation. Organ Procurement : Beating Heart Harvest ✪ S/p Aortic Cross Clamp on donor’s heart preservation solution and ice is placed on the heart and speedy return to the recipient’s hospital ★The result is a portable device that functions as a miniature coronary perfusion system that supplies donor hearts with an oxygenated solution. The preserved heart is then reperfused using a modified ex vitro model named after its creator, Dr. Langendoor. Upon reperfusion of the donor hearts, measurements of contractility, left ventricular function and myocardial metabolism can be done. Additional studies are being conducted to evaluate the nature of reperfusion injury and identify variables to prevent it.

Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006 “The International Society of Heart and Lung Transplantation Guidelines for the Care of Heart Transplant Recipients.” It appears in The Journal of Heart and Lung Transplantation, Volume 29, Issue 8 (August 2010), p 914-956

Recommendations for the Evaluation of Donor/Recipient Histocompatibility: Class I 1 Screening panel reactive antibodies (PRA) should be performed in all HT candidates. When the PRA is elevated (≥10%) further evaluation is recommended. Level of Evidence: C. 2. The specificity of circulating antibodies should be determined with a solid-phase assay such as flow-cytometry, if possible, in a regional certified human leukocyte antigen (HLA) laboratory. Level of Evidence: C. 3. The complement fixation capability of detected antibodies should be reported. Level of Evidence: C. 4 .The anti-HLA class I and II specificities (ie, any HLA antibody directed against HLA-A, HLA-B, HLA-Cw, HLA-DR, and HLA-DQ antigens) should be defined. In the absence of international standards, each transplant center must define the threshold of antibody levels used to define which specific donor HLA antigens confer an unacceptable rejection risk. Level of Evidence: C. 5. The virtual crossmatch, which compares recipient anti-HLA antibody specificities with donor HLA antigens, should be routinely used

Post Operative Care The sinoatrial nodes of the donor and recipient remain intact, and both are present within the recipient. For 3 weeks after surgery, the electrocardiogram demonstrates 2 P waves; however, the heart rate and electrical activity of the new heart are purely dependent on the intrinsic electrical system of the heart and not on the neurological input from the recipient. Chronotropic and Inotropic support for the denervated graft, stunned; recovering from cold preservation ; ischemia reperfusion injury Parasympathetic interventions (carotid sinus massage, the Valsalva maneuver, or injection of atropine) have no effect on sinoatrial node activity or atrioventricular (AV) conduction. Antiarrhythmic agents that act at the AV node, such as digoxin and quinidine, are less effective than they would be in a native (innervated, nontransplanted) heart. The administration of adenosine is contraindicated after heart transplantation because it may result in prolonged asystole.

Post Operative Care Elevation of blood pressure by a selective alpha-agonist such as phenylephrine does not cause reflex slowing of the heart rate. Response to sympathomimetic amines that act indirectly by releasing catecholamines from nerve terminals (dopamine, ephedrine) is diminished. The response to direct beta-adrenergic agonists (isoproterenol, dobutamine, epinephrine, and norepinephrine) is qualitatively preserved. However, prolonged inotropic support of the donor heart depletes its myocardial catecholamine stores, so the cardiac allograft often requires higher than usual doses of even direct-acting catecholamines

Sinus Node dysfunction Sinus node dysfunction resulting in bradycardia is common during the first 2–3 postoperative days, until the graft recovers from ischemia reperfusion injury. Most bradyarrhythmias resolve over 1–2 weeks, but complete re-innervation takes months to years, if ever. Recovery may be further delayed in patients who received preoperative amiodarone. Isoproterenol has been replaced by the more predictable dobutamine as the mainstay in providing postoperative pharmacologic pacing. Some patients may require temporary pacing, and very rarely a permanent pacemaker may need to be inserted. Theophylline has been used to increase heart rate and facilitate weaning of chronotropic support after heart transplantation. Ventricular ectopy is common, and tachyarrhythmias should be treated by the usual pharmacologic methods . However because of the propensity for bradycardia, amiodarone should be used only if external or transvenous pacing is in place. It is also noteworthy that ventricular irritability and arrhythmias are important signs of acute cardiac allograft rejection .

Complications Bleeding from the suture lines. This is a rare occurrence but may require reexploration in the early postoperative period. Hyperacute rejection can occur immediately after blood flow is restored to the allograft and up to 1 week after surgery despite therapeutic immunosuppression. Infection is the primary concern in transplant patients.

Cardiovascular Post Operative Complications Good Graft Function: CI, PAP, CVP, Normal or even Hyperdynamic Adequate peripheral perfusion: U.O, Mentation, SVO2. TTE or TEE if any evidence of impaired graft function

Cardiovascular Post Operative Complications LV Failure RV Failure Acute TR Supraventricular Arrhythmias Cerebrovascular injury Acute Kidney Injury

Postoperative LV failure Ischemia-reperfusion injury (myocardial stunning) is the most common cause of post-CPB and, primary graft dysfunction may also be induced by inadequate graft preservation. In addition to reperfusion injury, acute rejection should always be considered and aggressively pursued by further evaluation including echocardiography and endomyocardial biopsy. Inotropic agents such as dobutamine, epinephrine, and milrinone are useful as supportive therapy. In severe cases, an intraaortic balloon pump (IABP) may be helpful for short-term support until recovery from ischemia-reperfusion injury. But if there are signs of end-organ injury, there should be a low thresholdfor placement of a short-term ventricular assist device (VAD) as a bridge to recovery or retransplant .

Recommendations for Peri-operative Vasoactive Drugs Use in Heart Transplant Recipients Class I: 1. Continuous 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. 2. The following therapies are suggested: a. isoproterenol, 1 to 10 mcg/min, or b. dobutamine, 1 to 10 mcg/kg/min dopamine 1 to 10mcg/kg/min, or c. isoproterenol, 1 to 10 mcg/min dopamine 1 to 10mcg/kg/min, or d. milrinone, 0.375 to 0.75 mcg/kg/min Level of Evidence: C. 3. Continuous infusion of a-adrenergic agonists including phenylephrine, norepinephrine, or epinephrine can be used to maintain adequate mean arterial pressure. Level of Evidence: C .4. Low dose vasopressin (0.03–0.1 U/min) or methylene blue can be added to a-agonist for vasodilatory shock Level of Evidence: B.

Right Ventricular Failure Indeed, RV failure accounts for more than half of all cardiac complications and 20% of all early deaths following heart transplantation . Many patients undergoing heart transplantation have long-standing secondary pulmonary hypertension with elevated pulmonary vascular resistance (PVR) that is exacerbated intraoperatively by CPB, blood transfusion, and vasoconstrictor catecholamines. The donor right ventricle is naive to elevated PVR and may easily fail in the immediate post-CPB and -operative period. The likelihood of RV failure is exacerbated by small donor heart size, inadequate RV preservation, and especially if PVR is 480 dyne-sec-cm-5. Post -operatively, it may be induced by overzealous transfusion of blood, blood products or fluid, mechanical obstruction of the pulmonary artery anastomosis, or acute rejection.

Differential Diagnosis of RV Failure Acute Cardiac tamponade; occurs in post op bleeding cases and rapid transfusion Hypotension, Low CI, elevated CVP: TEE for dd

RV Failure Acute RV failure is a devastating event Progressive cardiovascular collapse. The free wall of the RV is thin  distends when the ventricle fails CVP becomes progressively elevated. Severe RV dilation shifts the interventricular septum into the left ventricle,  impairs its filling decreases LV stroke volume low cardiac output syndrome: elevated CVP ; easily confused with acute cardiac tamponade. Early diagnosis with TEE is of paramount importance. Uncorrected RV failure: anasarca, hepatic congestion and acute kidney injury rapidly progresses to multisystem organ dysfunction and failure.

The principles of management of RV Failure Vasopressor support of MAP to improve RV coronary perfusion Inodilator therapy with milrinone and dobutamine to enhance contractility and decrease PVR, and RV afterload reduction with INO or prostacyclin. diuresis Successful therapy is evidenced by decreased CVP, RV size, and septal shift, and relief of anasarca

Hemodynamic Management of the Transplanted Heart The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients Recommendations for the Medical Management of Right Ventricular Dysfunction and Pulmonary Vascular Hypertension After Heart Transplantation The Journal of Heart and Lung Transplantation, Volume 29, Issue 8, August 2010, Pages 914-956 Maria Rosa Costanzo, Thomas Dengler, et al.

Recommendations for the Medical Management of Right Ventricular Dysfunction and Pulmonary Vascular Hypertension After Heart Transplantation Class I 1. Inotropic agents that can be used to augment right ventricle (RV) function include isoproterenol, milrinone, enoximone✪, dobutamine, and epinephrine. ✪Enoximone is a selective phosphodiesterase inhibitor ( type III) with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. Approved in UK Level of Evidence: C. Class Iia 1 Systemic vasodilators with pulmonary vasodilating properties, including nitroglycerine and sodium nitroprusside, can be used in the absence of systemic hypotension. Level of Evidence: C. 2. Selective 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.

Acute Tricuspid Regurgitation The rate of moderate-to-severe tricuspid regurgitation is reported to be as high as 50% at 5 years.

Recommendations on the Management of Peri-operative Tricuspid Valve Regurgitation Class I: 1. Tricuspid 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 Closely monitored for the first few post-operative days. The frequency of sub- sequent follow-up should be guided by clinical and hemodynamic variables. Level of Evidence: C. Class II: 1. DeVega annuloplasty of the donor tricuspid valve (TV) can be considered to maintain the normal size of the TV annulus. Level of Evidence: C. The Journal of Heart and Lung Transplantation, Volume 29, Issue 8, August 2010, Pages 914-956 Maria Rosa Costanzo, et al.

Supraventricular Arrhythmias Atrial fibrillation or flutter occurs in 20%–30% of patients after cardiac surgery, but the incidence is much lower after heart transplantation. The most likely explanation is cardiac denervation and pulmonary vein isolation; bradycardia, brad- yarrhythmias, and conduction defects are much more common. Post operative atrial fibrillation, when it does occur, may be a harbinger of acute rejection.

Recommendations for the Peri-operative Management of Cardiac Arrhythmias in Heart Transplant Recipients Class I: 1. Pharmacologic chronotropic agents, including isoproterenol and theophylline can be used in the peri-operative setting to increase heart rate. Level of Evidence: B. 2. Atrial 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. 3. After HT, temporary pacing should be initiated in the setting of relative bradycardia to maintain heart rates of > 90 beats/min. Level of Evidence: B. 4. Pacing guidelines of the American College of Cardiology (ACC)/American HeartAssociation (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. 5. Treatment of tachyarrhythmias should be aimed at rate control. Level of Evidence: B

Recommendations for the Peri-operative Management of Cardiac Arrhythmias in Heart Transplant Recipients 6. Persistent tachyarrhythmias, whether atrial or ventricular, should prompt investigation of possible rejection and electrophysiological evaluation if rejection is absent. Level of Evidence: B. 7. Sustained ventricular tachycardia (SVT) should be eval- uated with both an angiogram and an endomyocardial biopsy (EMB). Level of Evidence: B. Class IIa: 1.The 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 2.Non-dihydropyridine calcium channel blockers (CCBs) and β-blockers may be used in HT recipients for rate control. Level of Evidence: B.

Cerebrovascular Injury A quarter of all patients undergoing heart transplantation show some form of postoperative neurologic or cognitive impairment. In about 5%–14% of patients, the neurologic defect is focal, i.e., overt stroke, and is associated with increased morbidity, 1-year mortality and decreased long-term survival . Prevention, early detection, and early treatment are the keys to improving outcome.

Acute Kidney Injury Most recipients have some degree of preexisting renal insufficiency as a consequence of chronic heart failure. Most important determinant of renal outcome is cardiac graft function: if it is good, AKI is rare, but if it is poor, AKI is inevitable. Injudicious administration of nephrotoxic calcineurin inhibitors (cyclosporine A, tacrolimus) in patients with hypovolemia or low cardiac index exacerbates AKI. If early AKI is recognized, an alternate form of induction therapy (e.g., basiliximab) can be used with a suitable delay in initiation of calcineurin inhibitor therapy. Mild nephrotoxic AKI usually responds to cautious hydration and decreasing the dose of calcineurin inhibitor.

Recommendations on the Peri-operative Use of Mechanical Circulatory Support After Heart Transplantation: Class I: 1. Mechanical 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. 2. MCS 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. 3. Support for either LV or RV failure should escalate from pharmacotherapy to IABP to MCS. Level of Evidence: B. 4. Small ventricular assist devices (VADs) such as the TandemHeart and Levitronix Centrimag can provide ad- equate support for RV, LV, or biventricular (BiV) failure, and have benefits of ease of implantation, management, and explant. Level of Evidence: C.

The TandemHeart Percutaneous Transseptal Ventricular Assist System (PTVAS). Copyright 2011  Cardiac Assist Inc.  The TandemHeart continuous flow consists of 3 subsystems: A catheter set, which includes a 21F venous inflow cannula that is inserted transseptally into the left atrium to aspirate oxygenated blood A 9-17F arterial perfusion catheter that returns blood from the external pump to one or both femoral arteries; an external continuous flow pump, which provides flows of up to 5 L/min at a maximum speed of 7500 rpm; an external controller, which is used to program and control the pump. The device can remain implanted for up to 3 weeks, and patients are confined to their beds for the duration of support.

Tandem Heart pump Cardiac Assist, Inc Instead of using conventional mechanical roller bearings, this design features a hydrodynamic fluid bearing that supports the spinning rotor. The fluid bearing is supplied by a unique lubrication system which feeds a nominal 10 cc/hr of saline to which an anticoagulant (typically heparin) has been added. The fluid acts as a coolant and lubricant for the seal which separates the rotor chamber from the blood chamber, and the anticoagulant is delivered to the blood chamber precisely at the seal interface to minimize the risk of thrombus formation.

Levitronix CentriMag LVAS The Levitronix CentriMag short-term LVAS comprises a single-use centrifugal pump, a motor, and a primary drive console. Compared to other devices, the Levitronix LVAS is unique in that it is designed to operate without mechanical bearings or seals. This is possible because the motor magnetically levitates the impeller, achieving  rotation with no friction or wear.

The Pump The Levitronix CentriMag is a continuous-flow, centrifugal-type rotary blood pump that is placed outside the body (extracorporeally). The pump housing and rotor are made of medical-grade polycarbonate, designed for single-use. The only moving component within the pump is the impeller, which is magnetically levitated and rotated in a contact-free manner. The centrifugal pump design permits rotation of the impeller at lower speeds, while still achieving desired flow rates. The pump can rotate at speeds of 1500 rpm to 5500 rpm and can provide flow rates of up to 9.9 liters per minute. The Levitronix pump causes very little damage to the blood because it does not contain any bearings or seals—components that are known to cause hemolysis and promote thrombus formation.

Allograft vascular disease Main cause of late graft failure and death. The coronary arteries develop a progressive concentric myointimal hyperplasia. This hyperplasia can develop as early as 3 months after transplantation. The cause of the process is unclear. CMV infection and recurrent rejection episodes are thought to be associated with the cause. The initial ischemia/reperfusion injury of the allograft coupled with repeated rejection episodes might contribute to the process. The only available therapy is retransplantation. The process can sometimes be treated by stenting of the diseased vessels

Immunosuppression Initial induction phase followed by life-long maintenance Triple therapy: 1) Corticosteroids (methylprednisolone, prednisone) SE: glu intolerance 2) Cell cycle inhibitors/antimetabolites ( Azathiaprine, mycophenolate) SE: bone marrow depression: severe thrombocytopenia or leucopenia 3) Calcineurin inhibitors ( cyclosporin A, tacrolimus) when pt has enteral access. SE: dose dependent nephrotoxicity in IV depletion, neurotoxic manifestations.

Immunosuppression For difficult induction or acute rejection SE: SIRS and Anaphylaxis Interleukine-2 (IL-2) antagonists ( basiliximab or daclizumab) Monoclonal antilymphocytic antibody (OCT-3) Polyclonal antilymphocytic antibody ( Thymoglobulin)

Immunologic mechanisms/sites of action. Sista and Wall Postoperative Cardiac Care, edited by Robert N. Sladen, MD, Lippincott Williams & Wilkins, Baltimore © 2011.

TABLE 12-2. Immunosuppression after heart, heart-lung, and lung transplantation (66–69) Agent Dosage Target Level Dosage Adjustment Corticosteroids Methylprednisolone sodium succinate (Solu-Medrol) 0.5–1.0 g IV prior to perfusion of the allograft 125 mg IV every 8 hr 3 doses on ICU admission Daily taper regimen (e.g., 50 mg, 40 mg, 30 mg IV every 12 hr or equivalent taper) Prednisone 1 mg/kg PO given in divided doses daily, on transition IV methylprednisolone Co-Induction agents (anti-CD25 monoclonal antibody; interleukin-2 inhibitors) Daclizumab Basiliximab 1 mg/kg IV in OR with methylprednisolone Repeat on POD 7 and every other week 3 (total of 5 doses) Purine synthesis/cell cycle inhibitors Mycophenolate mofetil (CellCept) Start on POD 0 with 0.5–1.0 g IV every 12 hr Transition to PO when possible Hold for WBC 5000/mm3 Decrease or hold if diarrhea and GI intolerance Azathioprine (Imuran) Start on POD 0 with 1.0 mg/kg IV daily Transition to 2.0 mg/kg PO daily when possible Hold for WBC 5000/mm3 Calcineurin inhibitors Tacrolimus (FK506, Prograf) Start on POD 1 with 0.5 to 1.0 mg PO twice a day. Delay if serum creatinine is increasing. 12–15 ng/mL If level 12 ng/mL, increase dose by 0.5 mg twice a day If level 15 ng/mL, decrease dose by 0.5 mg twice a day Cyclosporine A (Neoral, Gengraf, Sandimmune) Start on POD 1 with 2.5–5.0 mg/kg PO twice a day. Delay if serum creatinine is increasing 350–400 ng/mL If level is 350 ng/mL, increase dose by 25 mg twice a day If level is 400, decrease dose by 25 mg twice a day GI gastrointestinal; ICU intensive care unit; IV intravenous; PO oral; POD postoperative day; OR operating room; WBC white blood count.

Nosocomial Infections Bacterial infections are the most common source of sepsis in the first month after transplantation, surgical site infections, ventilator-associated pneumonia, empyema, and catheter-related infections (blood stream and urinary tract). Agents: methicillin-sensitive and methicillin-resistant Staphylococcus aureus enteric gram-negative organisms that include lactose fermenters (Klebsiella, Escherichia coli, and Enterobacter) and non- lactose fermenters (Pseudomonas, Proteus, and Acinetobacter). Legionella infections are rare, but may occur if the water supply becomes contaminated.

Opportunistic infections CMV is the single most important pathogen after the first month following solid organ transplantation. Primary infection is most severe in a CMV-negative recipient who receives a graft from a CMV-positive donor (CMV mismatch). Routine prophylaxis is initiated immediately with intravenous gancyclovir (which appears to be superior to acyclovir), with transition to the oral prodrug valganciclovir when possible. If active infection is suspected, intravenous CMV immune globulin is administered as well

Opportunistic infections Pneumocystis carinii (now known as Pneumocystis jiroveci) is an important cause of opportunistic pneumonia. Prophylaxis is provided with trimethoprim-sulfamethoxazole; in patients who have sulfa allergy or intolerance, inhaled pentamidine or oral atovaquone are alternatives Fungal infection, especially aspergillosis, occurs frequently after lung transplantation, especially when a greater intensity of immunosuppression is needed to treat episodes of early acute rejection. Prophylaxis with inhaled amphotericin B is routinely used in these patients while hospitalized

Anesthesia for Patients With Previous Transplant Transplanted patients require anesthetic for surgical procedures that may or may not be cardiac related Preoperative evaluation includes extensive reevaluation of cardiac function Systolic function is usually normal but a significant number of patients develop diastolic dysfunction, manifested as exercise intolerance Abnormalities in isovolumic relaxation time correspond with varying degrees of rejection Increased peak inflow velocity and mitral deceleration are indicators of restrictive filling Rejection causes inflammatory infiltrate that causes edema The presence of rejection increases perioperative morbidity and the incidence of asymptomatic arrhythmias Complication related to immunosuppression should be considered, including opportunistic infections Immunosuppressants side effects include nephrotoxity as well as neurotoxicity and cyclosporin is associated with cholelithiasis, increasing the incidence of cholecystectomy in these patients Repeated biopsies for routine transplant management may cause injury to the tricuspid valve with severe tricuspid regurg Often requires tricuspid valve replacement

Anesthesia for Patients With Previous Transplant Choice of anesthetic depends on the type of surgery and condition of the patient Regional anesthesia can be used cautiously, with the knowledge that these patients cannot mount the usual response to vasodilation and hypotension Cardiovascular monitoring is dependent on the nature of the planned surgery. Invasive monitoring is not necessary for minor procedures. Intraoperative echocardiography is important in managing volume status. The ECG may have a double P wave, reflecting atrial activity in the native atrial cuff and the transplanted atrium Cardiac output of the transplanted heart is preload dependent and rely on changes in stroke volume. Ephedrine or isoproterenol should be readily available to treat bradycardia as atropine will not have an effect. Patients with prior heart transplantation have undergone successful pregnancies

References 1.Postoperative Cardiac Care, edited by Robert N. Sladen, MD, Lippincott Williams & Wilkins, Baltimore © 2011. Assistant Editor Michael Fanshawe, MBBS (Hons I), FANZCA with 43 contributorsopyright 2011 SOCIETY OF CARDIOVASCULAR ANESTHESIOLOGISTS 2. The International Society of Heart and Lung TransplantationGuidelines for the care of heart transplant recipients Chair: Maria Rosa Costanzo, MD J Heart Lung Transplant 2010;29:914–956 3. Heart Transplantation Treatment & ManagementAuthor: Donald M Botta Jr; Chief Editor: John Geibel, MD, DSc, MA