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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5212_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Introduction
- •Contents
- •Renin-Angiotensin Inhibitors: ACE Inhibitors (ACEi), Angiotensin Receptor Blockers (ARB), and Combined ARB/Neprilysin Inhibitors (ARNi)
- •Beta-Blockers
- •Mineralocorticoid-Receptor Antagonists
- •SGLT2 Inhibitors
- •Editor and Contributors
- •1 Medical Therapy for Patients with End-Stage Heart Failure
- •Abstract
- •Clinical Pearls
- •Introduction
- •Medical Therapy for Heart Failure with Reduced Ejection Fraction HFrEF
- •Diuretics/Fluid Management
- •Hydralazine and Isosorbide Dinitrate
- •Additional Medications
- •Device Management of Advanced Heart Failure
- •Cardiac Resynchronization Therapy
- •Indwelling Pulmonary Artery Pressure Sensors
- •Treatment of the Hospitalized Patient with Acute Decompensation
- •References
- •2 Mechanical and Surgical Options for Patients with End-Stage Heart Failure
- •Abstract
- •Clinical Pearls
- •Introduction
- •Ventricular Assist Device Categories: A Generational History
- •Trends in Ventricular Assist Device Use: Strategies and Outcomes
- •Contraindications to LVAD Insertion
- •Potential Adverse Events with Left Ventricular Assist Devices
- •Left Ventricular Assist Device Selection
- •Short-Term Options for Mechanical Circulatory Support
- •Intra-Aortic Balloon Pump
- •Extracorporeal Membrane Oxygenation
- •Percutaneous Mechanical Circulatory Support
- •Heart Transplantation
- •References
- •3 Evaluation for Heart Transplant Candidacy
- •Abstract
- •Clinical Pearls
- •Introduction
- •Indications for Heart Transplantation
- •The Evaluation
- •Assessment of Heart Failure Severity
- •Models to Predict Survival in Advanced HF Patients
- •Psychosocial Evaluation
- •References
- •4 Potential Contraindications to Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Heart Transplant Contraindications
- •Obesity
- •Malignancy
- •Pulmonary Hypertension
- •Primary Pulmonary Disease
- •Diabetes Mellitus
- •Renal Dysfunction
- •Hepatic Dysfunction
- •Cerebrovascular and Peripheral Vascular Disease
- •Frailty
- •Infections
- •Hepatitis B
- •Hepatitis C
- •Tuberculosis
- •Chagas Disease
- •Substance Use
- •Other Systemic Diseases
- •Psychosocial Evaluation
- •Financial Considerations
- •References
- •5 Listing Criteria and Optimization of the Pre-transplant Patient
- •Abstract
- •Clinical Pearls
- •Listing Process
- •Allocation Criteria
- •A Brief History
- •The 2018 Allocation Revision
- •Optimization of the Pre-transplant Patient
- •Medical Surveillance on the Waitlist
- •Immunological Optimization
- •Other Considerations for Patients on the Waitlist
- •References
- •6 Overview of Transplantation Immunobiology
- •Abstract
- •Clinical Pearls
- •Innate Versus Adaptive Immunity
- •Human Leukocyte Antigens Polymorphism and Nomenclature
- •Overview and Polymorphism of HLA
- •HLA Nomenclature
- •Alloantigen Presentation
- •Antibody Production and Biology
- •Endothelial Cell Activation by Antibodies
- •Tolerance
- •References
- •Methods of Assessment for HLA and Non-HLA Antibodies
- •Panel Reactive Antibodies
- •Virtual Crossmatch
- •Non-HLA Antibodies
- •Calculated PRA (cPRA)
- •Therapeutic Options for the Sensitized Patient
- •Plasmapheresis and Immunoadsorption
- •Intravenous Immune Globulin (IVIg)
- •7 The Sensitized Patient Awaiting Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Risk Factors for Sensitization
- •Clinical Implication of HLA Antibodies
- •Rituximab
- •Proteasome Inhibitors
- •Emerging Desensitization Strategies
- •Splenectomy
- •Eculizumab
- •Monitoring of Sensitized Patients While Awaiting Transplantation
- •Conclusions
- •References
- •8 Donor Organ Procurement and Preservation
- •Abstract
- •Clinical Pearls
- •Donation After Brain Death (DBD)
- •Donation After Circulatory Death (DCD)
- •Donor Referral and Evaluation
- •Donor Acceptability and Recipient Matching
- •DCD Heart Evaluation
- •Donor Heart Procurement
- •Direct Procurement and Machine Perfusion (DP/MP)
- •Normothermic Regional Perfusion (NRP)
- •Donor Heart Preservation
- •Normothermic Machine Perfusion
- •Controlled Temperature Static Storage
- •Hypothermic Machine Perfusion
- •References
- •9 Surgical Considerations in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Surgical Technique of Donor Heart Recovery
- •Biatrial Orthotopic Cardiac Transplantation
- •Indications
- •Technique
- •Bicaval Technique
- •Operative Technique
- •Heterotopic Heart Transplantation
- •Indications
- •Operative Technique
- •Special Considerations
- •References
- •10 Physiology of the Transplanted Heart
- •Abstract
- •Clinical Pearls
- •Introduction
- •The Autonomic Nervous System
- •Functional Anatomy
- •Parasympathetic Fibers
- •Sympathetic Fibers
- •Cardiac Pacemaker
- •Autonomic Physiology
- •Homeostasis of the Cardiovascular System
- •Exercise and the Denervated Heart
- •Allograft Response to Exercise
- •Exercise Protocols for the Heart Transplant Recipient
- •High-Intensity Interval Training
- •Reinnervation
- •Determinants of Reinnervation
- •Quantifying Reinnervation
- •Parasympathetic Reinnervation
- •Electrophysiology of the Transplanted Heart
- •Pharmacology of the Transplanted Heart
- •Beta-Blockers
- •Beta-Adrenergic Receptor Agonists
- •Atropine
- •Adenosine
- •Digoxin
- •References
- •11 Immediate Post-operative Management After Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Recommended Hemodynamic Monitoring
- •Causes of Cardiac Allograft Dysfunction
- •Primary Graft Dysfunction
- •Management of Cardiac Allograft Dysfunction
- •Management of Vasoplegia
- •Hyperacute Rejection
- •Intrathoracic Hemorrhage and Cardiac Tamponade
- •Pulmonary Hypertension
- •Electrical Monitoring
- •Sinus Node Dysfunction
- •Atrial Fibrillation
- •Ventricular Tachycardia
- •Non-cardiac Medical Issues After Heart Transplant
- •Renal Dysfunction
- •Neurological Dysfunction
- •Gastrointestinal Dysfunction
- •Antibiotic Use for Prophylaxis of Infection
- •Debility
- •Conclusions
- •References
- •12 Maintenance Immunosuppression Strategies in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction to Transplant Immunosuppression
- •Immunosuppressive Agents for Maintenance Regimens
- •Corticosteroids
- •Mechanism of Action
- •Calcineurin Inhibitors: Cyclosporine and Tacrolimus
- •Mechanism of Action
- •Notes
- •Drug Interactions
- •Antiproliferative
- •Azathioprine
- •Mechanism of Action
- •Mycophenolate Mofetil (MMF)
- •Mechanism of Action
- •Notes
- •Proliferation Signal Inhibitors (PSIs): Sirolimus and Everolimus
- •Mechanism of Action
- •Notes
- •Drug Interactions
- •Statins
- •Major Clinical Trials of Maintenance Immunosuppression Regimens—Which Agent to Use?
- •Comparison by Survival
- •Comparison by Incidence of Rejection
- •Individualizing Immunosuppression
- •Conclusions
- •References
- •13 Induction Strategies in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Depleting Antibodies
- •Polyclonal Antibodies
- •Monoclonal Antibodies
- •Non-depleting Antibodies
- •Basiliximab
- •Eculizumab
- •References
- •14 Minimization of Immunosuppression in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Sequelae of Immunosuppression
- •Minimization of Immunosuppression Strategies
- •Standard Maintenance Immunosuppression
- •Prednisone Weaning
- •Calcineurin Minimization
- •Use of Proliferation Signal Inhibitors to Reduce or Replace Calcineurin Inhibitors
- •Tacrolimus Monotherapy to Minimize Immunosuppression
- •Personalizing Immunosuppression
- •T Cell Immune Function Assay
- •Future Directions to Minimize Immunosuppression
- •References
- •15 Pre-transplant Screening and Post-transplant Infection Prevention in Heart Transplant Recipients
- •Abstract
- •Clinical Pearls
- •Pre-transplant Screening of the Donor and Recipient
- •Donor Screening
- •Bacterial Transmission
- •Fungal Transmission
- •Viral Transmission
- •Hepatitis B
- •Hepatitis C
- •Cytomegalovirus
- •Human T-Lymphotropic Virus
- •West Nile Virus
- •SARS-CoV2
- •Protozoal Transmission
- •Toxoplasma Gondii, Trypanosoma Cruzi (Chagas Disease)
- •Recipient Screening
- •Bacterial/Fungal/Viral Infections
- •Preventive Measures
- •References
- •16 Managing Infections After Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Bacterial Infections
- •Peri-Operative Prophylaxis
- •Gram-Positive Organisms
- •Staphylococci
- •Enterococci
- •Streptococcus Pneumoniae
- •Listeria Monocytogenes
- •Nocardia
- •Rhodococcus Equi
- •Mycobacteria
- •Gram-Negative Organisms
- •Aerobic Gram-Negative Bacilli
- •Legionella
- •Clostridium Difficile
- •Viral Infections
- •Peri-Operative Prophylaxis
- •Cytomegalovirus
- •Herpes Simplex Virus
- •Varicella Zoster Virus
- •Epstein Barr Virus
- •Community Respiratory Viruses
- •Hepatitis B
- •Hepatitis C
- •Other Viruses
- •Fungal Infections
- •Peri-Operative Prophylaxis
- •Candida Spp.
- •Aspergillus
- •Pneumocystis Jiroveci
- •Opportunistic Molds and Yeasts
- •Protozoa
- •Toxoplasma Gondii
- •Trypanosoma Cruzi
- •Clinical Approach to Infectious Features
- •Fever
- •Wound Infections
- •Urinary Tract Infections
- •CNS Infection
- •GI and Liver Infections
- •References
- •17 COVID-19 Considerations in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •COVID-19 in Heart Transplant Recipients
- •Management of COVID-19-Positive Heart Transplant Patients
- •Adjusting Chronic Immunosuppressive Therapies
- •Pharmacologic Therapies
- •Ritonavir-Boosted Nirmatrelvir (Paxlovid)
- •Remdesivir
- •Molnupiravir
- •COVID-19 Convalescent Plasma
- •Corticosteroids
- •Interleukin-6 Inhibitors and Janus Kinase Inhibitors
- •COVID-19 Vaccination Immune Paresis in Heart Transplant Recipients
- •Correlates of Protection
- •Waning Immunity and Variant Evolution
- •Strategies to Mitigate COVID-19 Vaccine Immune Paresis in Heart Transplant Recipients
- •References
- •18 Cardiac Allograft Rejection Surveillance
- •Abstract
- •Clinical Pearls
- •Introduction
- •Pathology and Diagnosis of Cardiac Allograft Rejection
- •The Endomyocardial Biopsy (EMB)
- •Procedural Technique
- •Procedural Limitations
- •Potential Complications
- •Scheduling of EMB
- •Histological Features of Allograft Rejection
- •Intragraft mRNA Transcript Diagnostics to Augment the EMB
- •Non-invasive Diagnostic Methods in Cardiac Allograft Rejection
- •Clinical Evaluation and Antibody Surveillance
- •Donor-Derived Cell-Free DNA
- •Electrocardiogram (ECG)
- •Echocardiography
- •Cardiac Magnetic Resonance Imaging (CMRI)
- •Biomarkers
- •Future Directions
- •References
- •19 Cardiac Allograft Rejection Treatment
- •Abstract
- •Clinical Pearls
- •Introduction
- •Acute Cellular Rejection (ACR)
- •Risk Factors for ACR
- •Treatment of ACR
- •Recurrent Cellular Rejection
- •Hyperacute Rejection
- •Antibody-Mediated Rejection (AMR)
- •Risk Factors for AMR
- •Treatment of AMR
- •Biopsy Negative Rejection
- •Late Acute Rejection
- •Future Directions
- •References
- •20 Medical Adherence and Outcomes After Heart Transplant
- •Abstract
- •Clinical Pearls
- •Introduction
- •Metrics of Compliance and Associated Challenges
- •Adherence and Heart Transplant Outcomes
- •Factors Associated with Poor Medical Adherence
- •Compliance with Lifestyle Habits
- •Interventional Strategies to Improve Adherence in Heart Transplant Recipients
- •Future Directions
- •References
- •21 Cardiac Allograft Vasculopathy
- •Abstract
- •Clinical Pearls
- •Epidemiology
- •Pathophysiology
- •Clinical Features
- •Diagnosis
- •Invasive Assessment of Cardiac Allograft Vasculopathy
- •Non-invasive Assessment of Cardiac Allograft Vasculopathy
- •Management
- •Medical
- •Interventional
- •References
- •22 Long-Term Complications in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Outpatient Management
- •Malignancy
- •General Medical Management
- •Cardiovascular Risk Factors
- •Renovascular
- •Endocrine
- •Gastrointestinal
- •References
- •23 Pediatric Cardiomyopathies
- •Abstract
- •Clinical Pearls
- •Dilated Cardiomyopathy
- •Hypertrophic Cardiomyopathy
- •Restrictive Cardiomyopathy
- •Oncological Cardiomyopathy
- •References
- •24 Pediatric Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Indications for Heart Transplantation
- •Candidate Evaluation
- •Anatomy
- •Pulmonary Vascular Resistance
- •ABO Incompatibility
- •Pre-transplant Sensitization
- •Infection
- •Other Organ Systems
- •Psychosocial Factors
- •Donor Selection
- •Wait List Management
- •Bridge to Transplant
- •Post-operative Management and Complications
- •Cardiovascular System
- •Respiratory System
- •Renal Function
- •Gastrointestinal System
- •Immunosuppression
- •Infection
- •Rejection Surveillance
- •Rejection
- •Long-Term Complications
- •Cardiac Allograft Vasculopathy
- •Infection and Malignancy
- •Survival and Outcomes
- •Equity
- •Summary
- •References
- •25 Adult Congenital Heart Disease—Special Considerations
- •Abstract
- •Clinical Pearls
- •Introduction
- •Challenges in Identifying Advancing ACHD-HF
- •Evaluation of the ACHD Patient Referred for Transplant Listing
- •Indications for Referral and Evaluation
- •Multi-disciplinary Evaluation
- •Role of the ACHD Cardiologist
- •HF Pharmacotherapy
- •Special Considerations for the ACHD Patient
- •Pre-transplant Hemodynamic and Vascular Assessment
- •Transplant Surgical Evaluation
- •Pulmonary Hypertension
- •Cyanosis
- •Sensitization
- •Liver Disease
- •Management of ACHD Patient Listed for Transplant
- •Mechanical Circulatory Support
- •ACHD Transplant Outcomes
- •References
- •26 Combined Heart and Other Organ Transplants
- •Abstract
- •Clinical Pearls
- •Introduction
- •The Ethics of Dual Organ Transplantation: Evaluating Fairness in Organ Allocation
- •Heart-Kidney Transplantation
- •The Pathophysiology of Cardiorenal Disease Leading to End Organ Failure
- •Safety Net
- •Outcomes of Heart-Kidney Transplantation
- •Management of the sHKT Patient
- •Heart-Liver Transplantation
- •Concerns for CHD Patients, Particularly the Fontan Population Who Require CHLT
- •Criteria to Proceed with CHLT
- •Surgical Approach and CHLT for Highly Sensitized Patients
- •Recommendations for Post-CHLT Management
- •Heart–Lung Transplantation
- •Indications for Heart–Lung Transplantation
- •Recipient and Donor Considerations for Heart–Lung Transplant
- •Management and Complications of Heart Lung Transplant Recipients:
- •Survival After Heart–Lung Transplantation
- •References
- •27 Pregnancy in Heart Transplant Recipients
- •Abstract
- •Clinical Pearls
- •Introduction
- •Preconception Counseling
- •Contraception
- •Assisted Reproductive Technology (ART)
- •Shared Decision-Making
- •Fatherhood After Transplantation
- •Risk Assessment, Management, and Outcomes of Pregnancy After Heart Transplantation
- •Timing of Pregnancy
- •Patient Risk Assessment
- •Surveillance
- •Baseline Evaluation of Graft Function and Risk Assessment
- •Surveillance of Rejection
- •Diagnosis and Treatment of Acute Rejection
- •Maternal and Fetal Outcomes
- •Maternal Outcomes
- •Fetal Outcomes
- •Management of Comorbid Conditions During Pregnancy
- •Diabetes
- •Hypertension
- •Infections
- •Immunosuppression During Pregnancy
- •Postpartum Management
- •References
- •Abstract
- •Clinical Pearls
- •Introduction
- •Historical Perspectives
- •Abiomed AbioCor TAH
- •Carmat Aeson TAH
- •BiVACOR TAH
- •Perioperative Management
- •Clinical TAH Outcomes
- •Summary and Future Directions
- •References
- •29 Xenotransplantation
- •Abstract
- •Clinical Pearls
- •History of Xenotransplantation
- •Xenograft Rejection
- •Hyperacute Rejection
- •Complement Activation
- •Acute Humoral Rejection
- •Acute Cellular Rejection
- •Graft Overgrowth
- •Infections
- •Ethical Considerations
- •References
- •30 Quality-of-Life After Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Introduction
- •Aspects of Quality-of-Life
- •Assessing Quality-of-Life
- •Physical Wellbeing
- •Functional Status
- •Employment
- •Operating Vehicles
- •Mental Health
- •Social Functioning
- •Reproductive Health
- •References
- •31 Patient Selection in the Context of Organ Scarcity
- •Abstract
- •Clinical Pearls
- •Introduction
- •Ethical Principles
- •Optimizing Donor and Recipient Risk Matching
- •Psychosocial Considerations
- •Financial Considerations
- •Balancing Individual and Societal Interests
- •References
- •32 Diversity and Access in Heart Transplantation
- •Abstract
- •Clinical Pearls
- •Map of Racial Disparities in Heart Failure Prevalence and Access to Advanced Therapies
- •Insurance Status and Access to Transplantation
- •Socioeconomic Stressors and Heart Transplant-Related Outcomes
- •The New Allocation System and Its Impact on Improved Access to Transplantation for Racial Minorities
- •Gender Disparities
- •Future Directions
- •References

94 P. Catarino
Donation After Brain Death (DBD)
Death may be determined in the patient who has
suffered a catastrophic brain injury on the basis
of coma, brainstem areflexia, and apnea. Since
brainstem function predicts the permanence of
coma, most of the testing focuses on demonstrating loss of brainstem reflexes (absence of
pupillary and corneal reflexes, absent response
to pain above the neck, and absent caloric
oculo-vestibular reflex). Apnea requires a setting of adequate stimulus for breathing, typically
hypercarbia. All testing requires the absence
of confounding factors such as hypotension,
hypothermia, metabolic derangements, or drug
effects. Diagnosis of brain death is primarily a
clinical diagnosis, with ancillary imaging only
performed as a backup measure. However, evidence of a brain injury compatible with brain
death is essential to the diagnosis. There are specific guidelines with a standardized approach to
testing applicable to particular jurisdictions [1,
2]. These patients are legally dead if confirmed
by brain death testing. At this point, they may be
referred for potential organ donation. The heart
continues to beat, and organ viability is maintained by mechanical ventilation and intensive
care measures.
Donation After Circulatory Death (DCD)
DCD refers to organ donation, which takes place
after a patient has been declared dead on the
basis of irreversible cessation of respiratory and
circulatory function [3]. For heart donation, this
is currently only feasible in the setting where
there has been a planned withdrawal of life-supporting therapies (WLST) following a determination of the futility of further active treatment.
These are referred to as Maastricht category III
donors to distinguish them from other potential
DCDs that occur in uncontrolled settings.
Here, the WLST is coordinated with the
organ procurement process. WLST is followed
by a decline in the patient’s vital signs, culminating in circulatory arrest. Death is determined
on the basis of mechanical (not electrical)
asystole—a flat arterial trace—and the absence
of breathing. After a standoff period, which is
usually 5 min, the absence of spontaneous autoresuscitation confirms permanence or irreversibility and allows confirmation of death. The
donor is transferred to the operating theatre for
organ procurement. There is no circulation, and
the organs all suffer a warm ischemic injury during this period.
Donor Referral and Evaluation
Organ donation represents a remarkable act
of compassion and solidarity for our fellow
man and maybe the final autonomous wish of
patients. Healthcare providers who deliver endof-life care have a duty to refer potential donors
to fulfill this wish. Intermediary organizations
take responsibility for the process of consent,
donor management and evaluation, and donor
allocation, removing any conflict of interest between those caring for potential donors
and those providing transplants to potential
recipients.
Potential donors require due diligence to
obtain as complete a picture as possible regarding their social and medical history and any condition that might be a contraindication to organ
donation. Standard laboratory tests, electrocardiograms, and chest X-rays are performed, as is
serology for a range of blood-borne pathogens
and human leukocyte antigen typing.
Specific testing for heart donors includes
transthoracic echocardiography. Coronary angiography may be performed selectively, usually
in donors with risk factors for coronary artery
disease, including age over 45 years. This may
be declined in the DCD setting, where invasive
testing may not be felt to be in the best interests
of the not-yet-deceased patient. In DCD, the
management of the patient continues under their
usual physicians, and the needs of the patient
remain the priority of care. In DBD, management transfers to the organ procurement intermediary team and may last many hours or days.
The period of donor evaluation is also one of

958 Donor Organ Procurement and Preservation
goal-directed intensive care management, with
attention to hemodynamics, fluid and electrolyte
management, and ventilatory parameters with
the aim of optimizing the viability of all organs.
Adjuncts such as steroid or thyroxine supplementation have been used historically, but there
is limited evidence of their effectiveness.
Donor Acceptability and Recipient Matching
The consideration of any donor's heart needs
to be made in the context of the recipient's
situation, with individual risk–benefit analyses carried out in each case. This requires an
understanding of the overall availability and
quality of donors. Individual transplant centers’ ability to absorb risk may also be a factor.
Standard acceptable donors are of age 45 years
or younger, with a normal echo [specifically
EF > 50%, normal valves, and no left ventricular hypertrophy (wall thickness < 14 mm)],
and normal hemodynamics [MAP > 60 mmHg,
CVP ≤ 12 mmHg and cardiac index > 2.4 L/min/
m2]. In some situations, extended criteria donors
would also be acceptable [4].
The up-to-date functional assessment of the
heart by hemodynamics and echocardiography
carries the most weight. This means that the circumstances of the death, for example, provoked
cardiac arrest with a long downtime or cardiopulmonary resuscitation and raised biomarkers,
would be mitigated by evidence of functional
recovery after the event. Brainstem coning at the
time of brain death results in a catecholamine
storm, which can impair ventricular function,
inducing a Takotsubo cardiomyopathy, which
may take days to resolve. Repeated evaluations
may be helpful.
ABO blood group matching to the recipient
is essential, as is size-matching. Predicted heart
mass provides the best metric for size-matching
accounting for age, gender, height, and weight
[5]. Online calculators are available. Generally,
up to 10% under-sizing relative to the recipient's predicted heart mass would be acceptable,
whereas more than 15% under-sizing would be
too small. Increased risk factors such as high
pulmonary vascular resistance in the recipient,
the presence of a durable left ventricular assist
device, and longer ischemic time would, however, influence this decision, as would other features of the donor.
Logistic factors will also come into play, particularly the predicted ischemic time. Ischemic
time in DBD starts at the time of application of
the aortic cross-clamp in the donor. It includes
the time for cardioplegia flush and cardiac
explant, travel time between donor and recipient centers, and time for implant in the recipient until the recipient's aortic cross-clamp is
removed. Ischemic times over 4 h correlate with
a higher incidence of primary graft dysfunction. The use of normothermic or hypothermic
machine perfusion has been shown to mitigate
risk in extended criteria donors, more challenging recipients, and long-predicted ischemic
times [6, 7].
DCD Heart Evaluation
The evaluation of DCD hearts follows similar principles to those outlined above for DBD
hearts. Two main differences exist:
1. Only around 50% of patients suffer circula-
tory arrest following WLST within the time
permitted, typically two hours. Therefore,
the prediction of which donors will decline
in a suitable time is part of their acceptabil-
ity. Several scoring systems exist but have
not proved clinically useful. Glasgow Coma
Score (GCS) = 3 is associated with around
a 2/3rds chance of rapid decline, but over-
breathing on the ventilator reduces this prob-
ability. A low PaO2:FIO2 ratio is one of the
strongest predictors.
2. There is an inevitable warm ischemic injury
prior to procurement. Once the donor's sys-
tolic blood pressure drops below 50 mmHg,
“functional warm ischemia” ensues, which
continues until the donor's heart is perfused
(either with blood or with cardioplegia). To
maximize functional recovery, this period

96 P. Catarino
should be kept below 30 min. This warm
ischemic injury results in a substantial depletion of the metabolic substrate in the donor
heart. The need to replenish these substrates
prior to transport means that standard procurement strategies for DBD (i.e., cardioplegia followed by cold static storage) are
poorly effective in DCD. Warm ischemic
injury means that, until now, mainly standard
criteria for hearts as defined for DBD have
been accepted in the DCD setting. It remains
to be seen what the results will be with
extended criteria DCD hearts.
Donor Heart Procurement
DBD
Standard DBD heart procurement is performed
by beating the heart and supporting the circulation in the setting of a multi-organ procurement
[8]. It is essential that there is good communication between teams and that equipment is
prepared, such as adequate field suction, to facilitate visualization during the period of organ
flush. Sternotomy is followed by opening the
pericardium and visualizing the heart, including
right and left ventricular distension wall motion
and coronary artery palpation. This visualization
is usually sufficient to determine acceptability
but may be augmented by direct pressure measurements, e.g., left atrial and even pulmonary
artery catheter measurements. At this point, the
recipient team can be given the go-ahead to start
the recipient procedure.
The surgical technique of donor heart procurement will be detailed in Chap. 9. The
explanted heart is moved to the back table to be
prepared for transportation. In the great majority of cases, the heart is placed in a cold crystalloid solution surrounded by ice in a series of
sterile containers, known as cold static storage.
The goal of preservation in this setting is to minimize metabolic demand by producing a rapid
mechanical and electrical arrest and inducing
hypothermia. The actual cardioplegia solution
would appear to be central to achieving these
goals; however, limited evidence is available to
support any particular solution.
DCD
There are two distinct protocols that have been
developed for the procurement of DCD heart.
Direct Procurement and Machine Perfusion (DP/MP)
This technique requires rapid explant of the
heart and ex-situ warm blood re-perfusion. The
TransMedics Organ Care System (OCS) Heart
device is the only device currently available to
achieve this. Donor blood is required to prime the
device, and so the first step in surgery is to aspirate 1.2–1.5L of donor blood from the right atrium
without any contamination from solutions used to
flush the other organs, especially the liver. Once
this is collected, the heart and other organs can be
flushed, the heart with 500–1000 ml of cold crystalloid cardioplegia (Del Nido and St Thomas’
solution are the most used, sometimes supplemented with GTN and erythropoietin). The heart
is explanted as described above for DBD, with a
longer main pulmonary artery preferred and high
placement of the cardioplegia cannula so that this is
excised when the aorta is transected. The explanted
heart is moved to the back table, which is prepared
for connection to the OCS heart device [9].
Normothermic Regional Perfusion (NRP)
This technique involves the rapid in-situ reperfusion of all the organs while excluding the
cerebral circulation. The term TA-NRP is used
to emphasize thoracic and abdominal organ
perfusion. The donor is cannulated for cardiopulmonary bypass, usually draining the right
atrium and re-infusing oxygenated blood into
the ascending aorta. The aortic arch branches are
clamped or ligated and may be vented, thereby
preventing cerebral perfusion. A modified extracorporeal membrane oxygenation circuit with a
hard-shell reservoir is used.

8 Donor Organ Procurement and Preservation
97
Fig. 8.1 Advances in Donor Heart Preservation.
Reprinted from Journal of the American College of
Cardiology, 79(11), Ersilia M. DeFilippis, Kiran K.
Khush, Maryjane A. Farr, Amy Fiedler, Arman Kilic,
The DCD heart typically re-animates within
one minute of NRP, which is then continued
for around 40 min, with the aim of correcting
the metabolic imbalance that has accumulated
in the agonal and circulatory arrest periods.
During this time, the lungs can be re-intubated
and recruited, and a bronchoscopy can be performed. The abdominal surgical preparation can
continue, and the external iliac arteries can be
ligated to augment visceral perfusion. The NRP
can then be weaned off, allowing the heart to
support the thoraco-abdominal regional perfusion. Functional assessment of the heart can be
carried out by visualization and basic hemodynamics, or more advanced measures applied like
Swan-Ganz catheterization and/or transesophageal echocardiography. The donor has now
become similar to a DBD donor, and further
procurement proceeds as it would in that situation, including cardiac preservation with cold
crystalloid cardioplegia and transportation in
cold static storage [10].
Michael M. Givertz, Evolving Characteristics of Heart
Transplantation Donors and Recipients JACC Focus
Seminar, 1108–1123., Copyright (2022), with permission
from Elsevier
Donor Heart Preservation
Standard preservation is cold static storage,
which involves placing the heart in a cold crystalloid solution surrounded by ice, which has
generally been considered safe for 4 h of total
ischemic time. Nevertheless, primary graft dysfunction may still occur even within this limit,
especially if there are other adverse features of
the donor organ. This has led to an increasing
use of alternative approaches to preservation
(Fig. 8.1). These include normothermic machine
perfusion, controlled temperature static storage,
and hypothermic machine perfusion.
Normothermic Machine Perfusion
The TransMedics Organ Care System for Heart
delivers normothermic blood perfusion to the
ex-situ heart. It is essential to the strategy of DP/
MP as described above [9] but is also useful in

98 P. Catarino
extended criteria DBD heart, particularly for prolonged ischemic times, increased donor age, and
reduced ejection fraction [6]. The device uses a
pulsatile pump to deliver oxygenated blood at
34 °C into the aorta and down the coronary arteries, recirculating the coronary venous return and
passing through the right atrium and right ventricle into a cannula in the pulmonary artery. The
left atrium is open and vented, so the left heart
is unloaded. The heart beats typically in sinus
rhythm, but it can also be paced. Adenosine is
infused to prevent coronary vasoconstriction,
and epinephrine is used to control aortic pressure. A wireless monitor displays real-time aortic pressure, coronary flow rate, temperature,
oxygen saturation, and hematocrit. Visualization
of wall motion is possible, although it must
be interpreted in the light of the left side not
being loaded and the right side only partially
so. Trends in the aortic pressure (65–90 mmHg)
required to achieve a given coronary blood flow
(650–850 ml/min), as well as the venous versus
arterial blood lactate levels, provide some functional assessment as surrogates for microvascular
function and cardiac metabolism. Preservation
times of 4–8 h are common. Once the recipient
is ready for the implant, the heart can be cooled
and re-arrested with cold crystalloid cardioplegia
prior to separation from the device.
The key studies that underpin the use of the
OCS Heart are the EXPAND trial and its continued access protocol, which showed that a high
proportion (87%) of extended criteria hearts could
be used with an acceptable safety profile, with
comparable outcomes to general HTx [5]; and the
US DCD Heart study which showed early outcomes for DCD HTx with a DP/MP strategy to be
comparable to those of general DBD HTx [9].
Controlled Temperature Static Storage
The Paragonix SherpaPak is designed to keep
the donor heart at 4–8 °C. The donor's heart is
suspended by the aorta in a cold preservation
solution container, which is placed in a sterile
canister around temperature-controlled packaging
elements. These elements contain a specialized
phase-change material that can absorb or release
heat and sustain the desired temperature range for
many hours. The transport device also monitors
and logs the temperature in the container. The
main premise of the technology is the avoidance
of freeze-induced injury, although increasing evidence supports better sub-cellular preservation at
temperatures higher than 0 °C [11].
The GUARDIAN-Heart registry is a manufacturer-supported international multicenter
database that allows for propensity-matched
cohort comparisons. These types of analyses
support a reduction in severe primary graft dysfunction and an improvement in one-year survival with the SherpaPak compared to standard
cold storage, particularly where ischemic time is
increased [12].
Hypothermic Machine Perfusion
The XVIVO hypothermic perfusion apparatus
consists of a reservoir from which a blood-based
perfusate is pumped with a roller pump through
an oxygenator, leucocyte filter, and heater-cooler
unit into the aorta of the donor heart. The perfusate is at eight °C and has a hematocrit of 15%.
The aortic pressure is controlled at 20 mmHg,
producing a coronary flow rate of 150–250 ml/
min. The device has been used in several clinical
studies in DBD transplants [7], in a small number of clinically directly procured DCD transplants, and in the first clinical xenotransplants.
References
1. Greer DM, Kirschen MP, Lewis A, Gronseth GS,
Rae-Grant A, Ashwal S, et al. Pediatric and adult
brain death/death by neurologic criteria consensus guideline: report of the AAN guidelines subcommittee, AAP, CNS, and SCCM. Neurology.
2023;101(24):1112–32.
2. Shemie SD, Wilson LC, Hornby L, Basmaji J, Baker
AJ, Bensimon CM, et al. A brain-based definition of
death and criteria for its determination after arrest of
circulation or neurologic function in Canada: a 2023
clinical practice guideline. Can J Anesthesia/Journal
canadien d’anesthésie. 2023;70(4):483–557.

998 Donor Organ Procurement and Preservation
3. Statement on Controlled Organ Donation After
Circulatory Death [Internet]. https://www.asahq.org/
standards-and-practice-parameters/statement-oncontrolled-organ-donation-after-circulatory-death.
Accessed 13 Oct 2024
4. Copeland H, Knezevic I, Baran DA, Rao V, Pham
M, Gustafsson F, et al. Donor heart selection: evidence-based guidelines for providers. J Heart Lung
Transplant. 2023;42(1):7–29.
5. Kransdorf EP, Kittleson MM, Benck LR, Patel JK,
Chung JS, Esmailian F, et al. Predicted heart mass is
the optimal metric for size match in heart transplantation. J Heart Lung Transplant. 2019;38(2):156–65.
6. Schroder JN, Patel CB, DeVore AD, Casalinova S,
Koomalsingh KJ, Shah AS, et al. Increasing utilization of extended criteria donor hearts for transplantation: the OCS Heart EXPAND trial. Heart Fail.
2024;12(3):438–47.
7. Rega F, Lebreton G, Para M, Michel S, Schramm
R, Begot E, et al. Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the
short-term outcome from a randomised, controlled,
open-label, multicentre clinical trial. The Lancet.
2024;404(10453):670–82.
8. Copeland H, Hayanga JWA, Neyrinck A,
MacDonald P, Dellgren G, Bertolotti A, et al. Donor
heart and lung procurement: a consensus statement.
J Heart Lung Transplant. 2020;39(6):501–17.
9. Schroder JN, Patel CB, Devore AD, Bryner BS,
Casalinova S, Shah A, et al. Transplantation outcomes with donor hearts after circulatory death. N
Engl J Med. 2023;388(23):2121–31.
10. Hoffman JRH, Hartwig MG, Cain MT, Rove JY,
Siddique A, Urban M, et al. Consensus statement:
technical standards for thoracoabdominal normothermic regional perfusion. Ann Thorac Surg. 2024.
11. Radakovic D, Karimli S, Penov K, Schade I,
Hamouda K, Bening C, et al. First clinical experience with the novel cold storage SherpaPak
TM
system for donor heart transportation. J Thorac Dis.
2020;12(12):7227.
12. D’Alessandro D, Schroder J, Meyer DM, Vidic
A, Shudo Y, Silvestry S, et al. Impact of controlled
hypothermic preservation on outcomes following heart transplantation. J Heart Lung Transplant.
2024;43(7):1153–61.

Surgical Considerations in Heart Transplantation
Fardad Esmailian and Andrew Lin
9
Abstract
Heart transplantation (HTx) represents one of
the seminal accomplishments of cardiac surgery. This chapter reviews the evolution of
surgical techniques for donor heart recovery
and HTx. We also shed light on surgical strategies to optimize outcomes of complex cases.
Keywords
Heart transplantation · Donor · Procurement ·
Brain death · Donor selection · Organ
preservation · Bicaval · Biatrial ·
Cardiothoracic surgery
Clinical Pearls
• Various surgical techniques for organ procurement exist, but key universal principles
include occluding or venting systemic and
pulmonary venous return, ensuring excellent
delivery of cardioplegia with rapid and effective arrest, prevention of ventricular distention, and avoiding injury to any structure that
is utilized in donor implant.
• The bicaval technique is the most common
operative technique for heart transplant in
the modern era, but the biatrial technique is
useful where dissection of the vena cavae is
hazardous.
• Transplant candidates with existing mechanical circulatory support devices or previous
sternotomies usually have significant mediastinal adhesions; in these situations, the operating team should be given sufficient time to
prepare the recipient to minimize ischemic
time.
• Any patient being considered for heart transplantation via redo sternotomy should have
a preoperative computed tomography scan
of the chest performed as part of the preoperative workup in order to better evaluate the
intrathoracic anatomy
Introduction
Heart transplantation (HTx) represents one of
the seminal accomplishments in the field of car-
F. Esmailian (*)
Cedars-Sinai Smidt Heart Institute, Los Angeles,
CA, USA
e-mail: fardad.esmailian@cshs.org
A. Lin
Aurora St. Luke’s Medical Center, Milwaukee, WI, USA
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
J. Kobashigawa (ed.), Clinical Guide to Heart Transplantation, https://doi.org/10.1007/978-3-031-88290-6_9
diac surgery. The first successful human heart
implant was performed on December 3, 1967,
by Dr. Christiaan Barnard in Cape Town, South
Africa. Several weeks later, Dr. Norman E.
101

102 F. Esmailian and A. Lin
Shumway of Stanford University performed the
first adult HTx in the United States [1]. Since
the era of these early pioneers, nearly all elements of the procedure have undergone significant modification and refinement. In 1983, the
use of cyclosporine and subsequent improvement in the medical management of organ rejection allowed HTx outcomes to improve as well
as the therapy to be widespread [2]. Currently,
over 4000 transplants are performed in the
United States annually. While organ procurement and preservation are discussed in Chap. 8,
we review surgical techniques for donor heart
recovery and HTx in this chapter.
Surgical Technique of Donor Heart Recovery
The donor is transported to the operating room
from the Intensive Care Unit with a secure airway and continuous monitoring. They are supine
with tucked arms and a slight pad under the
scapulae. Skin is cleansed, and sterile draping is
undertaken. A sternotomy is performed, taking
care to avoid injury to the underlying heart and
lungs. The pericardium is divided and retracted.
The heart may then be assessed for donor suitability, with special attention given to the size of
the organ, ventricular function, and evidence of
gross abnormalities such as trauma or coronary
artery disease. Various surgical techniques for
organ procurement exist, but key universal principles include (i) occluding or venting systemic
and pulmonary venous return, (ii) ensuring
excellent delivery of cardioplegia with rapid and
effective arrest, (iii) prevention of ventricular
distention, and (iv) avoiding injury to any structure that is utilized in donor implant. It is also
important to be conscientious of the needs of
the other organs undergoing procurement, such
as the length of the Inferior Vena Cava (IVC) for
the liver and lengths of the atrial cuff and pulmonary arteries (PA) for the lungs.
A typical operative sequence for procurement
in a brain-dead donor may proceed as follows:
(i) Mobilize the ascending aorta and encir-
cling with an umbilical tape to allow
separation from the underlying right pulmonary artery
(ii) Mobilize the superior vena cava (SVC)
and place a snare around it superior to the
azygos vein; dissect the azygos and ligate
with free tie
(iii) In conjunction with other organ procure-
ment teams, administer heparin and place
antegrade cardioplegia/pressure monitoring catheter in the ascending aorta and
connect arterial pressure monitoring line
(iv) When all teams ready, the SVC can be
snared with a Rummel tourniquet to limit
upper body venous return
(v) Pulmonary venous return is drained by
venting of the left atrium by rapidly transecting the pulmonary vein (our preference is the right superior or left inferior
when no lung team is present); in the
presence of a lung team, the left atrial
appendage or incision of the left atrium
between the orifice of the right pulmonary veins and Sondegaard’s groove
(vi) Incise the anterior IVC just above the
diaphragm
(vii) With the heart empty, cross-clamp aorta
and begin antegrade cardioplegia with
a goal aortic root pressure tracing of
60–80 mmHg (we believe it is important to measure the aortic root pressure to
ensure adequate delivery of cardioplegia
since finger palpation will not be accurate;
one must be extremely cautious in accepting the organ if the preservation solution
cannot be delivered with adequate aortic root pressure); place ice slush around
heart and complete the cardioplegia infusion ( approximately 15 cc/kg) while
checking for left ventricular distention

1039 Surgical Considerations in Heart Transplantation
(viii) Divide IVC at junction with right atrium;
divide left and right pulmonary veins or
left atrium if lungs are being procured;
divide ascending aorta distally, divide
pulmonary arteries, divide SVC distal to
the azygos vein; we recommend taking an
extended length of SVC for complex redo
cases
(ix) Inspect the heart on the back table for any
abnormality (e.g., patent foramen ovale,
valvular pathology), (xv) place the heart
in cold preservation.
In cases of procuring the heart and lungs, care
must be taken to avoid delivery of the pulmonary preservation solution into the coronary circulation. This can be achieved by dividing the
ascending aorta as soon as cardioplegia delivery
is completed and ensuring a very large incision
in the left atrial appendage and/or opening the
interatrial groove to aspirate the return from the
pulmonary veins.
Biatrial Orthotopic Cardiac Transplantation
Indications
The biatrial method represents the original
operative technique for HTx and was widely
utilized in the 1980’s. This operation has essentially been replaced by the bicaval method, but it
remains useful in certain surgical circumstances.
A review of the UNOS database by Davies et al.
revealed that the biatrial technique was associated with increased need for permanent pacemaker (OR 2.6, CI 2.2–3.1) and that the bicaval
technique was associated with improved 30-day
survival (OR 0.83, CI 0.75–0.93) [3]. The major
advantage of the biatrial technique in the modern era is for circumstances in which dissecting
out the SVC and IVC represent severe hazards,
such as in redo operations with dense adhesions.
Technique
The recipient is brought to the operating room,
and appropriate monitoring lines are inserted,
including arterial line and central venous line.
Once the donor’s heart is confirmed to be appropriate for procurement, the implanting team can
begin preparing for the implant operation. The
sternal incision is made 60–90 min prior to the
anticipated time of organ arrival, and preferably earlier in the setting of redo sternotomy.
The ascending aorta is typically cannulated
just proximal to the aortic arch, but the axillary
or femoral arteries may prove useful in special circumstances such as a heavily calcified
ascending aorta or a difficult preoperative mediastinum. The SVC and IVC are then snared and
cannulated distally to allow room for anastomoses. A left ventricular vent may be placed at the
discretion of the implanting surgeon to avoid
rewarming of the heart by the blood returning from the pulmonary veins from collateral
flow during the implantation. Once the donor’s
heart is confirmed to have arrived safely, cardiopulmonary bypass is initiated, and the aorta is
cross-clamped. The native heart is then excised,
taking care to leave an appropriate cuff of tissue
along the aorta, PA, right atrium, and left atrium.
Any defibrillator leads are excised as proximal
as possible at this time without a forceful pull to
avoid tearing the SVC or innominate vein. The
donor’s heart is inspected on the back table and
assessed for any potential valvular abnormalities, a patent foramen ovale requiring closure,
or structural injury requiring repair. Once the
back-table preparation is complete, the organ
is removed from the ice bath and brought into
the surgical field. The left atrial anastomosis is
performed first. This suture line must be performed with meticulous attention to hemostasis, as accessibility is difficult upon completion
of the implantation. The donor’s right atrium is
then opened from the right atrial appendage to
the IVC, taking care not to injure the sinoatrial

104 F. Esmailian and A. Lin
node. The donor SVC is oversewn. The donor’s
right atrial cuff is anastomosed to the recipient’s
right atrium, starting directly over the left atrial
suture line and continuing circumferentially
along the atrial free wall. Next, one-half of the
PA anastomosis is performed, followed by the
aortic anastomosis. Several minutes prior to the
release of the cross clamp, systemic glucocorticoids (e.g., solumedrol) are administered. An
aortic root vent is placed, and the aortic crossclamp is then removed by venting the aortic root
to prevent the introduction of air into the coronary circulation. After reperfusion of the donor
graft, the remaining half of the PA anastomosis
is completed if not previously performed in its
entirety. The patient is then weaned off cardiopulmonary bypass after initiation of the inotropic support and de-airing of the left ventricle.
Protamine is administrated, and decannulation is
performed in the standard fashion. A partial left
pericardectomy can be performed to decrease
the chance of significant pericardial effusion
in the postoperative period, especially in cases
where there is a very large pericardial space in
comparison to the size of the donor organ. The
defibrillator generator and the remnant of the
pacing leads, if present, are then removed with
the chest still open. Chest tubes and pacing
wires are placed. Hemostasis is optimized, and
the wound is closed. An illustrative comparison
between the biatrial and bicaval techniques is
demonstrated in Fig. 9.1 [4].
Bicaval Technique
reperfusion to reduce warm ischemic time. The
aortic anastomosis is completed, and the crossclamp is released. The remaining PA anastomosis is completed. The donor SVC is then opened
into the azygos vein to allow a large anastomosis
and prevent postoperative stenosis. Care must
be taken to keep the orientation of the SVC and
avoid any kinking. The anterior anastomosis of
the IVC is then completed. Weaning from cardiopulmonary bypass is initiated, and the operation is completed, as discussed previously.
Heterotopic Heart Transplantation
Indications
Heterotopic HTx is not widely utilized and is
useful only for select circumstances. Accepted
indications include (1) irreversible high pulmonary vascular resistance (PVR) in the recipient
and (2) severe donor-recipient size mismatch.
A potential third indication in the future may
include xenotransplant bridging, as immunomodulation advances may eventually make this
a feasible option. As the donor graft serves to
augment the native heart, it functions as a de
facto bi-ventricular assist device. One advantage of the heterotopic technique is preservation
of the native heart as a safety margin in case of
graft dysfunction. Recognized complications
include a high incidence of ventricular dysrhythmias, anatomic compression by the graft (e.g.,
right lung), and a high incidence of premature
structural deterioration of the donor organ [5–7].
Operative Technique
Preparation of the recipient mediastinum is
largely similar to the biatrial technique, with
the major alteration being the isolation of the
SVC and IVC. The SVC is divided at the cavoatrial junction, and the free wall of the right
atrium is trimmed to allow for a sewing cuff just
above the true IVC. The left atrial anastomosis
is performed first, followed by the IVC and PA
anastomoses. The posterior portions of the IVC
and PA anastomoses can be performed prior to
Operative Technique
Cardiopulmonary bypass is established, and the
right pleura is incised. An opening is made on
the donor’s left atrium just below the interatrial
groove, and this is anastomosed to a cuff of the
recipient’s right pulmonary vein. A longitudinal
incision is then made on the recipient’s right
atrium and extended to the SVC. The donor
right atrium and SVC are similarly incised, and
a running anastomosis is performed. The donor
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