Introduction
Definition of heart failure- Heart failure (HF) is a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality, which is confirmed by either elevated natriuretic peptide levels or objective evidence of pulmonary or systemic congestion. As per the Left Ventricular Ejection Fraction (LVEF), HF can be classified as given in Figure 1.1, 2
The global burden of heart failure
HF is considered a global pandemic, with approximately 64.3 million people suffering in 2017.3
Heart transplant data
Heart transplantation provides the best outcome for acute or end-stage heart failure. Approximately 8988 heart transplants occurred in the year 2022 worldwide, as per data from ‘The Global Observatory on Donation and Transplantation’ (GODT).
According to the ‘NHS Organ and Tissue Donation and Transplantation Activity Report 2022-2023’ (data from 1st April 2022 to 31st March 2023) there were 325 new heart transplant registrations in the UK. Out of the 695 patients on the heart transplant waitlist- 384 were still on the waitlist or were suspended temporarily, 212 patients received heart transplants, 81 patients were removed from the waitlist, and 18 patients died while on the waitlist.4
The data from ‘The Organ Procurement and Transplantation Network (USA)’ states that, there are 3434 heart transplant waitlist candidates in the USA as of 20th May 2024. There have been 1445 heart transplants in USA in the year 2024 till 20th May 2024. While there was a total of 4545 heart transplants in 2023. 5 In the year 2020, 76% of candidates were on the waiting list for less than 1 year. Whereas, the proportion of candidates awaiting a transplant between one to two years, rose from 7.6% to 11.7%. 6
Indications for transplant
The most common indication for heart transplants has been end-stage non-ischaemic cardiomyopathy followed by ischaemic cardiomyopathy. The other indications being valvular heart disease, congenital heart disease, hypertrophic cardiomyopathy, restrictive cardiomyopathy.7, 8
Wait time for transplant
As per ‘OPTN/SRTR 2022 Annual data report: Heart’, about 45.8% patients had waited time of <90days in USA. With waitlist time ranging from 0 days to >2 years.9
Survival and morbidity post-transplant
As per ‘The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult heart transplantation report- 2019’ the median survival after adult heart transplants performed between years 2002 and 2009 is 12.5 years. Median survival of 14.8 years is seen in recipients surviving the first-year post-transplant. 60% of the surviving recipients were not re-hospitalization in the 1st year, and approximately 75% did not require re-hospitalization in the 2-5 years post-transplant.10
As per 'The registry of the International Society for Heart and Lung Transplantation: thirty-first official adult heart transplant report-2014', 1-year survival was 81% and 5-year survival was 69%, for transplants between 1982- June 2012.11
The common long-term causes of mortality after transplantation are graft failure, non-cytomegalovirus infection and multiple organ failure. Other causes of death being malignancy, acute rejection, cardiac allograft vasculopathy, and renal failure.10
Due to increasing donor heart requirements, a few countries such as Australia, America, Spain, UK have started accepting hearts from Donation after Circulatory Death (DCD).12 Prognosis of heart transplant recipients from a DCD donor are similar to from Donation after brain Death (DBD), however there is higher need for postoperative mechanical circulatory support.13
In an effort to promote organ donations, there is an increase in the number of countries with an opt-out method of organ donation protocol (e.g. Argentina, Chile, Columbia, Singapore, UK, Spain, France, etc). Here, every citizen is considered a willing prospective organ donor (in the event of death) unless the person or family specifically opts-out from donation.
The Indian Experience
On 16 February 1968, Dr. P.K. Sen and his team performed the first human heart transplant in India at ‘Seth G. S. Medical College & King Edward Memorial Hospital, Mumbai (erstwhile Bombay)’. It was the fifth cardiac transplant worldwide, and he was the fourth surgeon in the world to perform this historical procedure.14, 15 This was immediately followed by the 6th worldwide transplant by the team.16
The Transplantation of Human Organs Act, was passed in 1994, which allowed donation from Brain dead donors (DBD).17 This was followed by first successful heart transplant in India from a brain-dead donor was performed by Dr. P. Venugopal on 3rd August 1994 at the ‘All India Institute of Medical Sciences, New-Delhi’.18
Dr. K.M. Cherian performed heart transplant on 22nd-23rd September 1995, in Chennai, the first heart transplant surgery to be performed in a private hospital in India.19 The first heart-lung transplantation in India was done at Madras Medical Mission, Chennai on 3rd May 1999 by Dr. K.M. Cherian’s team.20, 21, 22
Dr. Jose Chacko Periappuram performed the first heart Re-transplant in Kochi, on 6th March 2014.23
Figure 2 shows Indian data for the total number of heart transplants from the year 2013 to 202224
Figure 2
Data for organ donation and transplantation (2013-2022)
(National organ & tissue transplantation organisation, DGHS, Ministry of Health & Family Welfare, Govt. of India)
Table 1 shows the Indian number of organ donation, organ utilization and heart transplants that occurred in the year 2022.
Anaesthesia Perspective
Management of heart transplant recipients from the Anaesthesia perspective is challenging due to a myriad of patient risk factors; and the urgent nature of surgery due to the unpredictable nature of donor heart availability.
The intraoperative aim is safe induction of anaesthesia, strict asepsis, immunosuppressive therapy, the anticipation of major vascular injury, managing pulmonary vascular resistance, ventricular support, optimal ventilatory strategy, and good haemostasis.
The postoperative goal is preventing infection, haemodynamic management, gradual weaning of supports, adequate analgesia, monitoring for complications, physiotherapy, and early discharge of the patient from the intensive care unit.
There is an increased complexity of heart transplant recipients due to the increasing use of pre-transplantation mechanical circulatory support devices, the number of patients with congenital heart diseases, redo-surgeries, multi-organ transplants, etc.25 The cardiac anaesthesiologist needs to know about the modern changes in the field of Heart Transplant.
In this review, we describe the peri-operative anaesthesia considerations in adult heart transplant recipients.
Indications and Contra-indications for heart transplantation.2, 26, 27
Table 2
Indication and contra-indication for heart transplantation
Allocation Criteria
In India, the hospital is expected to perform required investigations of potential heart, lung, and heart-lung transplantation recipients. Who are then registered on the ‘NOTTO portal-www.notto.gov.in’ by the hospital. Registered recipients are classified as per the Priority listing for organ allocation. Priority allocation criteria for heart, heart-lung: National Organ & Tissue Transplantation Organisation (NOTTO), Govt of India is described in Table 3. 28
Table 3
Priority allocation criteria for heart and heart-lung recipients (NOTTO, Govt of India)
Organ procurement & transplant network (OPTN) heart allocation criteria, USA is described in Table 4.29
Table 4
Adult heart allocation criteria (OPTN, USA)
Preoperative Evaluation & Workup
A detailed history of the present illness is taken, including its duration, and severity. The need for hospitalization, medication for heart failure or arrhythmia, current need for inotropes, presence of pacemaker/Implantable cardioverter defibrillator (ICD), and mechanical circulatory support devices. Aetiology of functional Heart Failure, Heart failure severity grading, and Presence of mechanical abnormality of the heart (e.g. ischaemic, valvular, cardiomyopathy, congenital heart disease) need to be elucidated.
History of Pulmonary pathology- presence of COPD, Asthma, Pulmonary arterial hypertension, Pneumonia, Obstructive sleep apnea.
Central Nervous System History- Carotid stenosis, Syncope, Stroke, Transient Ischaemic attack.
Assessment for Metabolic syndromes- Diabetes, Hypo-hyperthyroidism, autoimmune diseases, etc.
Assessment of Renal function- h/o renal failure, renal replacement therapy.
Assessment of Hepatic function- the presence of congestive hepatomegaly, cirrhosis, primary liver or gall bladder pathology.
Any other significant medical history e.g. recent infections, treated Tuberculosis, treated Malignancy.
Previous Surgeries for congenital heart disease (palliative/corrective), valvular surgery, Coronary artery bypass grafting, previous lung surgeries, Peripheral vascular surgeries and any other surgery.
Medication history- Current cardiac medications e.g. diuretics, digoxin, ace inhibitors, beta-blockers, inotropes, antiplatelets, anticoagulants, and antiarrhythmics. Pulmonary medications for asthma, pulmonary vasodilators. Anti-diabetic medication, Insulin, Thyroid medications. Antibiotics/Anti-viral drugs.
Anaesthesia history- h/o tolerance to general anaesthesia, and regional anaesthetics.
Note H/o drug allergy, transfusion (Allo-sensitization to blood products).
Ask about past or current H/o smoking, alcohol, drug abuse, and psychological or cognitive disabilities.
Measurements of- Weight, Height, BMI assessment, Frailty assessment, Blood pressure, heart rate and rhythm.
Investigations: Investigations for pre-transplant workup are mentioned in Table 5 . 32, 33, 34
Table 5
Pre-transplant workup investigations
[i] CPET: Cardio pulmonary exercise testing; RER: Respiratory exchange ratio; PASP: Pulmonary artery systolic pressure; CT: Computed tomography; PT/INR: Prothrombin time/ International normalized ratio; aPTT: Activated plasma thromboplastin time; PSA: Prostate-specific antigen; HBs Ag: Hepatitis B surface Antigen; HBs Ab; Hepatitis B surface Antibody; HBc Ab Hepatitis B core Antibody; Hep C Ab: Hepatitis C Antibody; HIV: Human Immunodeficiency Virus; IgG: Immunoglobulin G
General consultations obtained from- Psychiatry, Social work, and other clinical services as needed (e.g. Nephrology, Pulmonology, Department of Infectious Diseases, Gastroenterology, etc.)
Table 6
Describes the pre-transplant optimisation protocol for recipients34
Anaesthesia Assessment30, 31, 35, 36, 37
Patient assessment is done as part of a multidisciplinary workup after the patient is listed. The next screening assessment is just before transplant. Screening of history, current status, assessment of systemic functions and recent investigations is done.
Last oral intake is confirmed. General airway assessment is done.
Patient status whether ambulatory, bedridden, or haemodynamically unstable in the intensive care unit is noted.
The severity of Left and Right ventricular dysfunction, pulmonary hypertension, intercurrent deterioration, recent angina, volume status, inotrope requirement, and severity of end-organ damage is assessed.
Recent Haemoglobin, coagulation parameters, platelets, liver and renal function, Blood glucose, infection screen with antibiotic sensitivity reports are assessed along with Transthoracic ECHO, angiography, pulmonary function tests, Cardiac Computed tomography, cardiac catheterization data.
Congenital heart disease (CHD)- patients may be differentiated into those with uncorrected lesions, those who have undergone corrective or palliative surgery and those with a failing single ventricle physiology. May have limited sites for central venous access due to recurrent invasive procedures and abnormal anatomy. Assessment of CT chest is useful to plan venous cannulation, to note safe sternotomy routes, the presence of arterio-venous and veno-venous collaterals. Catheterization data can give further information about pulmonary vascular resistance, and aberrant pulmonary blood flow sources. Patients are screened for the presence of vascular thrombosis and infection foci.
Recurrent procedures or admission- Patients with recurrent central venous procedures have a predisposition to venous thrombosis. Venous Doppler sizing of femoral vessels is noted to prepare accessory sites of emergency peripheral cannulation.
Redosternotomy- History of Previous cardiac surgery is noted. The cardiac chambers might be stuck to sternum and there may be presence of extensive adhesions. The patient may be on anticoagulation (e.g. Fontan surgery or Valve replacement surgery) it predisposes to increased risk of bleeding, vascular injury during sternotomy. There are increased chances of vascular or major cardia chamber injury, bleeding, prolonged cardiopulmonary bypass time. External defibrillator pads, adequate blood products in operating room, rapid blood infusors, and preparation for emergency peripheral bypass should be arranged. Warfarin reversal might be considered.
Implantable Electronic devices- Cardiac Resynchronization Therapy (CRT), Implantable cardioverter defibrillator (ICD), and pacemaker is noted. Long duration of the device may predispose to lead fibrosis causing vessel narrowing. The leads may also be a nidus for infection. Respective company personnel are informed about the expected timing of surgery for device inactivation intraoperatively.
Mechanical circulatory devices- consists of IABP, ECMO, Ventricular Assist Devices (VAD). Patients may be on heparin, or warfarin. Vitamin K, Fresh Frozen plasma, and prothrombin complex concentrate may be required peri-operatively.37 Dissection around Ventricular assist devices might be difficult due to anticipated injury to the cardiac chambers.
Medication- patients on ACE inhibitors, Angiotensin Receptor blockers, Beta-blockers, Nitrates, Hydralazine may have perioperative hypotension or vasoplegia. Patients on warfarin, antiplatelet agents will be predisposed to increased bleeding; hence preparation for warfarin reversal, and increased blood product transfusion must be considered.
Consent- Informed written consent is to be taken for transplant, anaesthesia, risk of anticipated complications during surgery, invasive lines, blood transfusion, elective or emergency ECMO institution, unanticipated increase in ICU stay, immunosuppression-related complications, organ failure, renal replacement therapy, risk of morbidity and mortality.
Timing and Preparation of Surgery 37
In our Institute, the Pre-operative protocol is as follows:
Consent form and paperwork is confirmed. Fasting status is noted and patient is kept nil-by-mouth.
Leukocyte depleted, irradiated, CMV negative cross-matched 6 units each of packed RBC, FFP, and Platelet are arranged. Part preparation is done, along with nasal application of mupirocin ointment as MRSA prophylaxis.
Intravenous access is secured. Inj. Vitamin K 10 mg i.m. stat, Inj. Ceftazidime 1g i.v. stat, Inj. Teicoplanin 400mg i.v. stat, Tab. Thyroxine 25 mcg p.o. stat, and Tab. Mycophenolate mofetil 500mg p.o. stat is administered pre-operatively. Sedative agents are preferably avoided in an uncontrolled ward environment.
The goal of co-ordination at induction is to reduce graft ischaemia time, and pre-implantation time for the recipient to minimal. The donor heart should be inspected by the retrieval team, and the anticipated duration of donor heart travel time be calculated prior to anaesthetic induction of the recipient.
Approximately, 1 hour should be considered for induction of anaesthesia and 1 hour for surgical dissection. 2 hr of pre-implantation surgical dissection time should be considered for recipients undergoing redo-sternotomy.
Recipient heart explantation is undertaken only after the donor's heart is inspected at the recipient's operating room by the head surgeon.
Anaesthesia Management 31, 35, 36, 37, 38
A good co-ordination of the operating theatre team is of essence. The operating theatre team including Cardiac Anaesthesiologist, Senior Transplant Surgeons, Nurses, Technicians, Perfusionists should be available at induction. Company Technician must be available for CRT, Pacemaker, ICD interrogation, inactivation or reprogramming. In a patient with VAD, a practitioner trained in device management be present in the operating theatre till the device is removed.
Strict aseptic techniques are followed as the patient will be immunosuppressed post-operatively. Equipment and drugs are prepared as per routine on-pump cardiac surgeries. External defibrillator pads are to be applied. Standard monitoring (includes Pulse oximetry, 12 lead ECG, End-tidal CO2 monitor, Temperature monitor) and Cerebral oximetry using Near Infra-red Spectroscopy. Two Large-bore venous cannula and an arterial line is secured prior to anaesthesia induction. Ultrasound-guided Arterial line insertion can be done in the presence of Left VAD (due to non-pulsatile blood flow).
Central Venous Cannulation with Pulmonary Artery catheter placement after induction of anaesthesia (line should be secured before induction in very-high-risk patients). The right internal jugular vein may be reserved for future endo-myocardial biopsy access.
Preoperative inotropes, vasopressors, vasodilators, and pulmonary vasodilators infusions to be ready (e.g. Inj. Adrenaline, Nor-Adrenaline, Dobutamine, Nitrates, Milrinone, Levosimendan).2 Inotropes can be started just prior to induction to offset the sudden hemodynamic instability due to loss of intrinsic sympathetic tone, peripheral vasodilation, and negative inotropic effect of induction agents.
Induction: The aim at induction is to achieve rapid airway control with minimal myocardial depression and pulmonary vascular resistance, maintain systemic vascular resistance and preload.
The patient is considered to have a full stomach due to inadequate fasting and delayed gastric emptying. The modified rapid sequence induction is preferred for quickly securing the airway.
Patients may have exaggerated hypotensive responses to standard doses of sedative and opioid analgesics, and peak haemodynamic and hypnotic effects of drugs are delayed due to low cardiac output. Induction of anaesthesia must be gradual and titrated to effect, with adequate time for systemic drug circulation.
In our centre we use Inj. Midazolam 0.5mg i.v., Inj. Fentanyl 5mcg/kg i.v., Inj. Etomidate 0.25mg/kg i.v., Inj. Rocuronium 1-1.2mg/kg i.v. at Induction.
Ventilation- Tidal volume of 6-8ml/kg, adequate Positive end-expiratory pressure, a higher fraction of inspired oxygen (FiO2) used. Hypoxia, hypercarbia, atelectasis, and acidosis increase Pulmonary vascular resistance (PVR) which predisposes to RV failure. Nitrous oxide increases PVR, hence avoided intraoperatively.
Maintenance Anaesthesia
Other lines and monitors are placed after Anaesthesia Induction such as: -
Pulmonary Artery catheter (for cardiac output, mixed venous saturation, and PA pressure monitoring),
Orogastric tube (for gastric decompression),
Transoesophageal ECHO (for assessing bi-ventricular function, volume status, intra-cardiac thrombus, vegetations, valvular abnormality, shunts, effusion, aortic atheroma, adequacy of de-airing, readiness for weaning bypass etc.),
Foley’s catheter (for urine output measurement).
Balanced anaesthesia is maintained with air, oxygen mixture. Isoflurane, sevoflurane or propofol is used to maintain depth of anaesthesia. Inj. Fentanyl (for analgesia) and Inj. Rocuronium (for muscle relaxation) infusion is continued. Infusion of Inj. Atracurium as a muscle relaxant is used in patients with deranged liver and kidney function..
Hypotension is managed with fluid preloading and vasopressors for maintaining systemic vascular resistance, inotropes are added to increase cardiac contractility. Progressive haemodynamic instability may require urgent initiation of CPB. In patients with LVAD, a reduction in preload to the device may result in a low flow alarm. This is managed by intravenous fluid administration, followed by reduction in LVAD pump speed..
Antibiotics and immunosuppressants are administered after anaesthesia induction as per institutional protocol. Inj. methylprednisolone (1 gram i.v. is generally given after induction and 500mg i.v. at aortic cross-clamp release)..
Patients with a history of cardiac surgery have a higher risk of vascular injury at sternotomy. Femoral vessels are prepared before sternotomy for emergency initiation of peripheral Cardiopulmonary Bypass due to anticipated injury, bleeding and air embolism. Blood products are kept ready in the operating room. Cell saver and Rapid blood infusion system are on standby. An antifibrinolytic (Inj. Tranexamic Acid) is given to reduce bleeding and transfusion requirements.
Surgical Considerations
Sternotomy is followed by dissection of the aorta, pulmonary artery, Superior and Inferior Vena Cava. Pleural effusions are to be drained to reduce airway pressure. LVAD is to be mobilized. The Pulmonary Artery Catheter is withdrawn before Bi-Caval cannulation.
Before aortic cannulation, Inj. Heparin 400 U/kg i.v. is administered, to target activated clotting time > 480 sec.39 Heparin resistance can be managed by repeat heparin dose, Fresh frozen plasma administration, or antithrombin III concentrate (500 U i.v.) in patients with antithrombin III deficiency.40
High Aortic cannulation is done. Venous cannulae are placed in Superior and Inferior Vena Cava.
In Redo-surgeries, the femoral artery and femoral/axillary vein are cannulated for initiation of peripheral Veno-Arterial Bypass to decompress the heart, followed by central cannulation after cardiac dissection.
When the patient has been supported on an LVAD, at the time of transplant the patient is transitioned to CPB via standard Aorto-bicaval cannulation, CPB is commenced and outflow graft of the LVAD is clamped and the VAD is turned off. The Aorta is cross-clamped and the VAD hardware is removed from the surgical field.37, 41
The recipient's heart is explanted by transecting the Cavae, Aorta is transected proximal to the clamp, the pulmonary artery is transected prior to its bifurcation and the LA is transected keeping a broad cuff around the pulmonary vein which will be later matched to the donor LA cuff. Donor-recipient Aorta and Pulmonary Artery are anastomosed, Aortic cross-clamp is released. Then Donor-recipient SVC and IVC anastomosis is completed on a beating heart.42 Atrial and Ventricular pacing wires are fixed to the myocardium.
Preparation for Separating from CPB 30, 31, 36, 37
Inj. Methylprednisolone 500mg is administered just before cross-clamp release. Steep Trendelenburg position, and temporary mechanical carotid artery compression is achieved to prevent systemic air and debri embolism at cross-clamp release. 43 The Temporary pacemaker and transoesophageal echocardiography (TOE) machine is confirmed in operating room. Inotropes, vasopressors, and pulmonary vasodilators are kept available.
After cross clamp release, at least 1 hour reperfusion time is given to support the heart, especially for prolonged graft ischaemic time. While gradually rewarming (to >35.5degree centigrade) the patient on complete CPB, heart is allowed to eject while partly filled. ABG, Sr. electrolytes, Haemoglobin, Glucose levels are assessed. Lines are zeroed. De-airing of heart is confirmed using TOE.
Arrhythmias at cross-clamp release and weaning from CPB are managed by continued CPB support, increasing perfusion pressure, and maintaining Sr Potassium levels. Ventricular fibrillation or Ventricular tachycardia is managed by Internal defibrillation (10-30 Joules), Inj. Magnesium, Inj. Amiodarone and Inj. Lignocaine. Sinus bradycardia is managed by Inj. Isoproterenol i.v., Inj. Adrenaline i.v. or Atrial pacing.
Inotropic support
As the transplanted heart is denervated, there is a loss of direct sympathetic and parasympathetic input. The response to circulating catecholamines are blunted. Indirect-acting drugs (e.g. Atropine, glycopyrrolate, ephedrine) will not elicit a response. Cardiac output of denervated heart is dependent on chronotropy and preloading.
Following are the recommendations of medications as per ‘The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients, August 2010’ for support of transplanted heart.
Inj. Isoproterenol (1-10 mcg/min) i.v. (preferred due to chronotropic, inotropic, vasodilator activity), or
Inj. Dobutamine (1-10 mcg/kg/min) i.v. +/- Inj. Dopamine (1-10mcg/kg/min) i.v. or,
Inj. Isoproterenol (1-10 mcg/min) i.v. +/- Inj. Dopamine (1-10mcg/kg/min) i.v. or,
Inj. Milrinone (0.375-0.75mcg/kg/min) i.v. (inotropic, chronotropic, pulmonary>systemic vasodilator activity).
Vasoconstrictors such as Inj. Adrenaline (0.01-0.2 mcg/kg/min) i.v., Inj. Noradrenaline (0.01-0.3mcg/kg/min i.v., Inj. Phenylephrine i.v. can be used to maintain mean arterial pressure. Inj Vasopressin (0.03-0.1 Unit/min) i.v. or Inj. Methylene blue (1.5-2mg/kg) i.v. can be added to augment mean arterial pressure in case of vasoplegia resistant to the above vasoconstrictors.38, 44
Inhaled nitric oxide (iNO) at 10-20 ppm or Inhaled prostacyclin can be started as a pulmonary vasodilator (if low systemic pressures preclude the use of intravenous Milrinone) and to attenuate Primary graft dysfunction.
To reduce myocardial work, inotrope infusions are started at a low dose, along with pacing at 50-60 beats/min if heart rate is low.
Ventilation
The lung is recruited followed by the use of Lung protective ventilation strategy with FiO2 of 1 (eventually titrated to 0.6), Tidal volume 6-8ml/kg, PEEP 5cm H2O, and avoid high airway pressure. Measures to reduce pulmonary vascular resistance such as hyperventilation, hyperoxia, hypocarbia, alkalosis, avoidance of atelectasis, and avoidance of alveolar hyperdistention are ensured.
Transoesophageal echocardiography (TOE) is used to ensure de-airing of the heart, watch for intra-cardiac thrombus, and assess flow across anastomotic sites. Mid-oesophageal 4-chamber view is used while weaning CPB to assess LV and RV systolic/diastolic function, atrial and ventricular size, and degree of tricuspid/mitral regurgitation). Right ventricular failure on TOE can be assessed by evidence of RV dilatation, reduced RV ejection fraction, reduced free-wall contractility, tricuspid regurgitation, left shift of inter-atrial septum.
Slow weaning from CPB is started once-
Heart is adequately reperfused.
Patient is rewarmed, urine output assessed.
Haemoglobin, Electrolytes, ABG, Blood glucose levels are corrected.
TOE findings are acceptable.
12 lead ECG is shows regular sinus rhythm with no ST changes. Target heart rate of 100-110 beats/min is achieved. If donor heart rate is low, pacemaker is set to 90-110 beats/min, DOO mode)..
Inotropes, Vasoconstrictors, Pulmonary Vasodilators are optimised as per haemodynamics and TOE findings.
The PA Catheter is advanced into the pulmonary artery once CPB is weaned (pulmonary artery pressure, cardiac index and mixed venous oxygen saturation can be assessed).
Hemostasis is achieved, and drains are inserted. Hemodynamic stability is monitored during sternal approximation. Pacing is to be changed to DDD mode after chest closure.
Haemodynamic instability
can be due to RV and LV failure.
RV failure can be due to impaired RV systolic function or high PVR. RV failure management includes preload optimisation, PVR reduction, supporting RV contractility, maintain sinus rhythm and Atrio-ventricular synchrony, Ventilatory optimization. 45
Preload is evaluated by response of i.v. fluid to RV dimensions (on TOE) and central venous pressure (CVP). An increase in CVP beyond 15 mmHg may cause RV dilatation and tricuspid regurgitation.
Use of inotrope (e.g. dopamine, adrenaline)
Hypotension reduces RV perfusion pressure; It is managed by noradrenaline (to target Mean Arterial Pressure >60 mmHg).
Strategies to reduce PVR include optimizing ventilatory strategy, use of pulmonary vasodilators (e.g. Inj. Milrinone, inhaled nitric oxide, inhaled prostacyclin).
Table 7
LV systolic dysfunction and vasoplegia
LV dysfunction can be due to graft ischaemia, preexisting donor heart disease. Management includes inotropic support with reduction in systemic vascular resistance, and mechanical support with IABP or ECMO.
Vasoplegia (defined as hypotension in presence of normal LVEF, normal or elevated Cardiac index, refractory to increased filling pressure or high-dose vasopressors). Vasoplegia occurs in about 29% of patients after heart transplant.48 Predisposing factors are preoperative use of angiotensin-converting enzyme inhibitors, calcium channel blockers or amiodarone, presence of Left VAD or ECMO and prolonged Bypass time. Management includes vasopressors (Inj. noradrenaline and vasopressin) and Inj. methylene blue i.v.44
Mechanical circulatory support
Failure to wean from CPB due to borderline haemodynamics (MAP 65 mmHg, Cardiac Index <2L/min/m2, CVP >15mmHg) despite high inotropic support (e.g. Inj. adrenaline/noradrenaline >0.1-0.2 mcg/kg/min i.v.) is an indication for VA ECMO or temporary RV assist device in case of isolated RV dysfunction.37
Transfusion
Allosensitisation due to exposure to blood products is related to adverse outcomes post heart transplantation.49 Hence, blood conservation strategies are to be implemented, transfusion is to be given sparingly, and leucodepleted blood products are to be used. Cytomegalovirus (CMV) antibody-negative donor blood is used if the patient is Negative for CMV antibodies.37
Once Heparin is reversed with Inj. Protamine. Inj Tranexamic Acid (total dose of 20mg/kg i.v. intraoperatively) is repeated post CPB.50 Liver dysfunction, reoperations, VAD explant, and prolonged surgical time predispose patient to increased bleeding. Acquired von Willebrand syndrome in patients with VAD, respond to Inj. Desmopressin (0.3 mcg/kg i.v.).51
Packed RBCs, FFP, cryoprecipitate (or fibrinogen concentrate), and vitamin K use is guided by clinical assessment, preoperative coagulation status, amount of surgical dissection, CPB duration, and intraoperative values (of haemoglobin, platelet count, prothrombin time, activated partial thromboplastin time, point of care testing with thromboelastogram).
Post-operative Management
The goal of post-operative Intensive Care Unit (ICU) management includes maintaining haemodynamic stability, early extubation, maintenance of adequate analgesia, maintaining standard isolation and disinfection, antibiotic prophylaxis and immunosuppression, and monitoring for anticipated complications.
Future Directions52
There has been an increasing number of heart donations after circulatory death (DCD) with positive post-transplant results. These donations have also increased the donor pool.53
More data needs to be reviewed to assess the outcomes of Heart transplant from COVID-19-positive donor hearts.54
There is scope to increase the number of transplants in India by expanding government involvement, increasing public awareness for donation, public-private partnership for optimising transplantation process, infrastructure and skill building in government hospitals.
Studies in gene-edited pig-to-nonhuman primate (NHP) models, have provided encouraging data on pig heart survival with an anti-CD40m Antibody or an anti-CD154m Antibody immunosuppressive regimen.55, 56, 57, 58
There is in vitro evidence suggesting a weaker immune response when triple gene-knockout (TKO) pig organs (i.e., expression of three pig glycan xenoantigens is deleted) are transplanted into humans.59, 60, 61
Conclusion
The science of heart transplantation has evolved from an experimental procedure to an established standard of care for end-stage heart failure.
The preoperative assessment, intraoperative management, and postoperative management of heart transplant patients require an immense team effort and a robust transplant program.
Management of heart transplant recipients from the Anaesthesia perspective is challenging due to a myriad of patient risk factors; and the urgent nature of surgery due to the unpredictable nature of donor heart availability.
The cardiac anaesthesiologist needs to be well versed with the modern changes in the field of Heart Transplant.