Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5212_Библиотеки_им_академика_М_И_Перельмана.pdf
X
- •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

• Poorly controlled diabetes
• Less than 1 year post-transplant
• Nonadherence
• Uncontrolled hypertension
,
2
• Severe renal dysfunction (creati-
nine > 2.5 mg/dl, eGFR < 30 ml/min/1.73m
or dialysis)
• Significant proteinuria
• Inability to maintain therapeutic levels of
• Donor-specific antibodies
maintenance immunosuppression with CNI
• Heart transplant: cellular rejection in the
past year, any history of AMR, CAV grade 2
or greater
• Heart transplant: reduced EF (<30%), severe
• CMV infection within the past year
• Inability to stop mycophenolate products
valvular disease (stenotic lesions)
• Active infection
34927 Pregnancy in Heart Transplant Recipients
• Rejection may recur during pregnancy or after delivery and portends increased risk
• Graft dysfunction is associated with high risk of complications during pregnancy and a
risk of fetal CMV disease
• Pre-pregnancy DM, renal dysfunction and proteinuria are associated with higher risk of
preeclampsia
lial CM); special considerations for patients with pre-transplant diagnosis of PPCM
• Social history
History • Genetic condition may trigger need for genetic counseling (ARVC, HCM, CHD, fami-
Assessment Impact on management or outcome Contraindications to planned pregnancy
Table 27.2 Recommended baseline assessment of clinical status and graft function in lung transplant and heart transplant recipients desiring pregnancy
Clinical examination • Arterial hypertension is associated with higher risk of preeclampsia • Symptomatic graft dysfunction
• DM requires close monitoring to lessen risk for macrosomia and shoulder dystocia
Laboratory assessment: compre-
hensive metabolic panel, Hgb
A1c, urinalysis
Anti-HLA antibodies • Pregnancy could trigger alloimmunization
risk of rejection
• Sensitized patients have a worse long-term outcome
• Close monitoring of immunosuppression levels is recommended
Immunosuppressive levels • Trough levels of immunosuppression should be stable before pregnancy, to minimize the
• CMV seronegative patients should be advised to take additional precautions
Serology and PCR for CMV • Primary CMV infection and, to a lesser extent, CMV reactivation are associated with the
Standard assessment of graft func-
• CAV portends increased risk
worse long-term outcome
In-depth assessment of the graft
function (if clinically indicated)
with RHC/biopsy, coronary
tion with echocardiogram
angiogram
Souza et al., Reproductive health after thoracic transplantation: an ISHLT expert consensus statement, e1–e42, Copyright (2023), with
terization. Reprinted from The Journal of Heart and Lung Transplantation, 42(3), Kittleson, Michelle M., Ersilia M. DeFilippis, Catriona J. Bhagra, Jillian P. Casale, Matthew
Cauldwell, Lisa A. Coscia, Rohan D’
CMV = cytomegalovirus; DM = diabetes mellitus; EF = ejection fraction; HCM = hypertrophic cardiomyopathy; PPCM = peripartum cardiomyopathy; RHC = right heart cathe-
AMR = antibody-mediated rejection; ARVC = arrhythmogenic right ventricular cardiomyopathy; CAV = cardiac allograft vasculopathy; CHD = congenital heart disease;
permission from Elsevier

350 M. M. Kittleson
(continued)
EMB (preferably echo-guided) if rejection is suspected
week and then every
th
Every 4 weeks 24 h-monitoring of BP if hypertension is suspected
1–2 months until 24
4 weeks until delivery
Monitoring liver enzymes and platelet count if HELLP syndrome is suspected
Every 4 weeks Increase in eGFR is expected
Every 4 weeks Check for proteinuria
Every 4 weeks Additional therapy if increase in steroid dose is needed
Between 24 and 28 weeks May be performed earlier in patients at risk for diabetes
Additional therapeutic drug monitoring in the first two trimesters may be sugge-
sted, following daily dose adaptation, as needed
Every 4 weeks until 32nd week; every
2 weeks until 36th week; weekly until deli-
1–3 months after delivery Earlier testing of HLA-specific Ab if acute rejection during pregnancy
very and the first month after delivery
Every 4 weeks
Third trimester (36 0/7–37 6/7 weeks of
gestation)
Third trimester (36 0/7–37 6/7 weeks of
gestation)
Exam Timing Notes
Graft function and rejection
Physical examination, vital parameters
12-lead EKG Every 4 weeks EMB (preferably echo-guided) if rejection is suspected
Table 27.3 Timetable of periodic assessment during pregnancy in lung transplant and heart transplant recipients
Echocardiography At least every trimester and ideally every
Hypertensive disorders
Renal function, liver function, blood cells
count
Urinalysis
Diabetes mellitus
Fasting plasma glucose
Glucose challenge test
Immunosuppression
Circulating levels
HLA-specific antibodies
PCR for CMV genome Every 4 weeks
Infections
Urine culture Every 4 weeks
Complete blood count, CRP
Vaginal swab culture for Streptococci B
Serology for Toxoplasma (in seronegative
patients), HSV, hepatitis

35127 Pregnancy in Heart Transplant Recipients
In diabetic patients:
– consider closer monitoring of fetal growth from 28th week
– weekly monitoring from 32nd week
9 weeks of gestation when available
Nuchal translucency scan between 11 and
14 weeks gestation when available
Early (transabdominal or transvaginal)
anatomy scan between 11 and 16 weeks of
gestation when available
Every 2 months until 24th week; every
4 weeks until delivery
Exam Timing Notes
Fetal growth
Table 27.3 (continued)
Echo assessment of fetal well-being Routine dating ultrasound between 8 and
Abbreviations BP = blood pression; CMV = cytomegalovirus; CNI = calcineurin-inhibitors; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; EMB =
endomyocardial biopsy; HELLP = hemolysis, elevated liver enzymes, low platelets; HLA = human leukocyte antigen; HSV = herpes-simplex virus; PCR = polymerase chain
reaction. Reprinted from The Journal of Heart and Lung Transplantation, 42(3), Kittleson, Michelle M., Ersilia M. DeFilippis, Catriona J. Bhagra, Jillian P. Casale, Matthew
Cauldwell, Lisa A. Coscia, Rohan D’Souza et al., Reproductive health after thoracic transplantation: an ISHLT expert consensus statement, e1–e42, Copyright (2023), with
permission from Elsevier

352 M. M. Kittleson
(continued)
normal graft
function, no
LVEF reported
Before preg-
nancy: 5 (36)
During preg-
nancy: 3 (14)
[17]
8.2 ± 5.2
25.3 ± 5.8
0 (0)
Macera et al. [50] D’Souza et al. [51] Dagher et al. [16] Bhagra et al.
8.2 (2.6–24.6)
25.5 (17.6–33.3)
7.3 ± 4
28 ± 5.8
5.6
Not reported Not reported 16.0 (6.2–26.6) Not reported
33
61 (55–65) All with
All with normal graft function
but LVEF not reported
but no LVEF reported
2 (25)
During pregnancy:
– Before pregnancy:
Before pregnancy: 5 (45)
During pregnancy: 1 (6)
5 (39)
0 (0) During pregnancy: 1 (6) Before pregnancy:
1 (13)
During pregnancy:
2 (15)
Series (year) Punnoose et al. [6] (includes
Table 27.4 Summary of Maternal and Fetal Outcomes in Heart Transplant Recipients across contemporary published series, with > 10 reported pregnancies
TPRI data [5])
157 (91) 17 (11) 17 (16) 18 (8) 22 (17)
Number of pregnancies (number of
7 ± 6
women)
Unplanned pregnancies, n (%) 59 (46) Not reported Not reported 10 (56) 18 (82)
Mean time from transplant (years)
20 ± 8
27 ± 5.6
Mean age at transplant (years)
LVEF (%) pre-pregnancy Not reported All with normal graft function
Mean age at pregnancy (years)
During pregnancy: 72 (46)
Maternal complications (as % of pregnancies)
Hypertension, n (%) Before pregnancy: 65 (42)
Preeclampsia, n (%) 27 (23) 0 (0) 2 (12) 2 (15) 13 (4)
During pregnancy: 11 (7)
Diabetes mellitus, n (%) Before pregnancy: 7 (5)
2 (2) 0 0 0 (0) 0
Graft loss (within 2 years of deli-
Renal failure, n (%) Not reported Not reported 4 (24) Not reported Not reported
Infection, n (%) 22 (14) 0 (0) 2 (12) 3 (23) Not reported
very/termination), n (%)
Rejection, n (%) 14 (9) 0 (0) 2 (12) 0 (0) 1 (5)

35327 Pregnancy in Heart Transplant Recipients
[17]
immediate
postpartum
period from
postpartum
hemorrhage)
3.9 (2.6–5.4) Not reported
At 10 and 18 months after deli-
34 ± 4
very (attributed to rejection from
nonadherence with immunosup-
pression)
Macera et al. [50] D’Souza et al. [51] Dagher et al. [16] Bhagra et al.
TPRI data [5])
Series (year) Punnoose et al. [6] (includes
Table 27.4 (continued)
0 0 (0) 0 (0) 0 (0) 1 (during
Maternal Death during Pregnancy,
n (%)
9.4 (0.5–26) 11
Maternal death, n (%) 30 (33) 3 (27) 2 (12) 3 (38) 4 (24)
Mean time from pregnancy to
maternal death (yrs)
36 36.5 Not reported 35
Obstetric and Fetal outcomes (as % of pregnancies except as noted)
Live birth, n (%) 111 (69) 12 (71) 14 (81) 13 (72) 20 (91)
Mean gestational age at delivery
(weeks)
Fertility treatments used, n (%) Not reported Not reported Not reported Not reported 1 (5)
45 (42) 10 (83) 8 (46) 5 (39) 11 (55)
Cesarean delivery, n (% of live
births)
Miscarriage, n (%) 41 (25) 3 (18) 1 (6) 3 (17) 2 (9)
Ectopic pregnancies, n (%) 2 (1) Not reported Not reported Not reported Not reported
Terminations, n (%) 7 (4) 2 (12) 2 (12) 2 (11) 0 (0)
9 (8) * Not reported 2 (14%) ** 1 (8) 0
live births)
Duodenal atresia, tetralogy of Fallot, laryngomalacia, facial deformities, vermian hypoplasia of the cerebellum, hypospadias, cystic hygroma, pectus excavatum, lip and ton-
gue tie, and long QT syndrome
*
** Frontonasal dysplasia, bilateral radial ray anomalies with oligodactyly
Congenital malformations, n (% of
Low birth weight (<2500 g), n (%) 41 (37) 4 (36) Not reported 6 (46) 9 (45)
Preterm (<37 weeks), n (%) 45 (41) 4 (36) 6 (46) 7 (54) 9 (45)
*** Only fetal cardiac malformations noted; perimembranous ventricular septal defect
LVEF, left ventricular ejection fraction; TPRI, Transplant Pregnancy Registry International
Reprinted from The Journal of Heart and Lung Transplantation, 42(3), Kittleson, Michelle M., Ersilia M. DeFilippis, Catriona J. Bhagra, Jillian P. Casale, Matthew Cauldwell,
Lisa A. Coscia, Rohan D’Souza et al., Reproductive health after thoracic transplantation: an ISHLT expert consensus statement, e1–e42, Copyright (2023), with permission
from Elsevier

354 M. M. Kittleson
breastfeeding
No significant interactions with
CNI
be avoided during breastfee-
ding due to association with
depression
Beta-blockers may be less
well-tolerated in heart transplant
recipients due to denervation
with reduced exercise tolerance;
propranolol, metoprolol, and
labetalol have the lowest trans-
fer into breast milk
TID dosing may limit adhe-
rence; safe during breastfeeding
Should be avoided in the first
trimester (data about teratogeni-
city showed conflicting results);
may reduce milk volume during
breastfeeding
None
retention
To promote peripheral vasodilation Edema, headache, tachycardia Safe during pregnancy and
Sedation, dizziness, depression Safe during pregnancy; may
7 years
Postural hypotension
Bronchospasm (if history of asthma or
COPD)
To lower systemic vascular resistance (α-ant-
agonism is more pronounced than β-blocking
Fetal bradycardia, growth restriction
activity)
Often used for hypertensive crisis (intravenous)
decreasing their metabolism)
Hypovolemia, transient electrolytes and
metabolic disbalance in mother and fetus
To treat water retention
Complementary treatment in severe drug-re-
sistant hypertension and oliguria
Measure Rationale Potential side-effects Comments
Non-pharmacological
Low-sodium diet To prevent RAAS-mediated sodium and water
Pharmacological
Table 27.5 Treatment of hypertension during pregnancy in transplant recipients
Dihydropyridine calcium-channels blockers
Amlodipine
Nifedipine
Methyldopa Available data about safety in offspring up to
Beta-blockers
Labetalol
Hydralazine Peripheral vasodilatation May increase CNI trough levels (by
Diuretics
Loop diuretics
Thiazide diuretics
Bhagra, Jillian P. Casale, Matthew Cauldwell, Lisa A. Coscia, Rohan D’Souza et al., Reproductive health after thoracic transplantation: an ISHLT expert consensus statement,
e1–e42, Copyright (2023), with permission from Elsevier
Abbreviations CCB = calcium-channels blockers; CNI = calcineurin-inhibitors; COPD = chronic obstructive pulmonary disease; HT = heart transplantation; RAAS
= renin-angiotensin aldosterone system. Reprinted from The Journal of Heart and Lung Transplantation, 42(3), Kittleson, Michelle M., Ersilia M. DeFilippis, Catriona J.

35527 Pregnancy in Heart Transplant Recipients
Yes
breastfeeding
Continue treatment with corti-
Cleft palate may occur with high
Yes
costeroids when indicated
Frequent monitoring of levels
No teratogenic potential in human
10–15 mg prednisolone daily)
doses used in the first trimester (over,
(every 2–4 weeks)
registries
Limited evidence
Discontinue 6–12 weeks
before planned conception;
from animal studies
Not recommended
evaluate risk vs benefit on
case-by-case basis in heart
transplant recipients with CAV
Discontinue 6–12 weeks
No evidence of terato-
before planned conception or
immediately if unplanned
Relatively safe at contempo-
and congenital malformations
May use in place of mycophenolate
genic effect in human
studies
rary clinical dosing
depending on patient’s risk of rejection
dosing
Drug class Safety for use in pregnancy Risk of teratogenicity Special instruction Safety for use while
Table 27.6 Immunosuppressive agents in pregnancy
Corticosteroids Relatively safe at contemporary clinical
Relatively safe at contemporary clinical
dosing
Insufficient data to affirm safety Limited data in humans; potential risk
Calcineurin inhibitors
Cyclosporine
Tacrolimus
mTOR inhibitors
Everolimus
Sirolimus
No Teratogen: risk of spontaneous abortion
Mycophenolate products
Mycophenolate mofetil
human studies
Mycophenolate sodium
Azathioprine No evidence of teratogenic effect in
CAV = cardiac allograft vasculopathy; mTOR = mammalian target of rapamycin. Reprinted from The Journal of Heart and Lung Transplantation, 42(3), Kittleson, Michelle
M., Ersilia M. DeFilippis, Catriona J. Bhagra, Jillian P. Casale, Matthew Cauldwell, Lisa A. Coscia, Rohan D’Souza et al., Reproductive health after thoracic transplantation:
an ISHLT expert consensus statement, e1–e42, Copyright (2023), with permission from Elsevier.

356 M. M. Kittleson
done with lead draping of the abdomen [14].
Recommended regimens for the treatment of
acute cellular rejection during pregnancy include
high-dose corticosteroids; however, due to the
relative insulin resistance induced by pregnancy,
closer glucose monitoring is recommended if
steroids are used. The safety of other agents for
the treatment of rejection, such as anti-thymocyte globulin, in pregnancy has not been established and should be used with utmost caution.
Maternal and Fetal Outcomes
A key component of preconception counseling
is explaining the maternal and fetal pregnancy
outcomes. Table 27.4 provides a summary of the
key maternal and fetal outcomes in HTx recipients across a review of the largest series in the
literature.
Maternal Outcomes
HTx rejection is uncommon during pregnancy
but occurs more frequently after delivery.
Rejection rates in the peripartum period range
from 5 to 12% and episodes are most commonly
low grade without significant hemodynamic
compromise [5, 6, 16, 17, 50, 51]. Episodes can
often be treated with adjustments to baseline
immunosuppression and may be related to both
activation of maternal alloreactive T-cells and
subtherapeutic exposure to immunosuppressive
drugs, the latter being secondary to changes in
circulating blood volume, intestinal motility,
and renal function [17, 50]. However, rejection
in HTx recipients may also occur after delivery,
noted in 7% of patients within 3 months after
delivery [6]. The cause for rejection may be due
to variable immunosuppressant levels due to
increased blood volume.
The association between pregnancy and
the development of CAV is not clear. In 157
pregnancies in 97 HTx recipients, 2 individuals developed CAV after pregnancy, leading to
listing for re-transplantation, and 5 had CAV
or myocardial infarction listed as the cause of
death [6].
In a large series of HTx recipients, mortality during pregnancy was low at 0.5% [52].
However, the longer-term survival of HTx recipients after pregnancy warrants consideration. In
one analysis, 33% of HTx recipients who experienced pregnancy died with the median time
after first pregnancy to death of 8.9 years with
an average survival of 9.4 years [6]. In other
series, post-pregnancy mortality in HTx recipients ranges from 10.8% over 3–7 years followup [52] to 33% with 8.7 years of follow-up [5].
Notably, the mean age of the child at the time of
maternal death was 10.8 years [5].
Fetal Outcomes
The rate of miscarriage in HTx recipients
ranges can be as high as 25% [19, 52] compared to 16% in non-transplant pregnancies
[53]. However, several contemporary published
series have shown that with careful intrapartum management pregnancy in HTx recipients
can be successful with a reported live birth
rate between 69 and 91% [5, 6, 16, 17, 50–52].
Cesarean delivery occurs commonly in HTx
recipients, 39–83% [5, 19, 54]. Nonetheless,
about half of the infants in the published series
were delivered preterm, prior to 37 weeks
gestation, and 35–40% had low birth weight
(<2500 g) [5, 6, 16, 17, 50–52]. About 20% of
infants born to HTx recipients are admitted to
neonatal intensive care units [52] and 6.5–9%
have congenital anomalies [5, 52]. Data are limited regarding detailed longer-term follow-up of
offspring of HTx recipients.
Management of Comorbid Conditions During Pregnancy
Diabetes
Pregnancy can exacerbate pregestational diabetes
and lead to gestational diabetes with significant
impacts on both the fetus and pregnant individual [55]. Pregestational diabetes, both type 1 and
type 2, is associated with congenital anomalies
and both pregestational and gestational diabetes

35727 Pregnancy in Heart Transplant Recipients
are associated with fetal growth abnormalities, fetal growth restriction and macrosomia,
and fetal demise if glycemic control is poor
[56]. Pregestational diabetes is common in HTx
recipients; 21% develop diabetes within 5 years
of transplant [57] and up to 11% of HTx recipients have pregestational and gestational diabetes
[6, 17, 50]. This is not surprising, as pregnancy
is physiologically associated with insulin resistance, mediated by progesterone, cortisol, and
prolactin. Furthermore, compensatory increases
in insulin production may be impaired in transplant recipients, due to predisposing factors and
diabetogenic effects of calcineurin inhibitors
and steroids [58]. Consistent with recommendations from the American College of Obstetrics
and Gynecology (ACOG), screening for gestational DM should be performed at 24–28 weeks
in pregnant HTx recipients, potentially earlier in
those with an increased risk for diabetes [59, 60].
Treatment of DM during pregnancy should occur
in consultation with a maternal–fetal-medicine
specialist or an endocrinologist.
Hypertension
In HTx recipients, hypertension is common,
with a prevalence of 72% at 1 year and 92% at
5 years after HTx [61]. The pathophysiological mechanisms of post-transplant hypertension
are related to systemic and renal vasoconstriction resulting from calcineurin inhibitors as
well as cardiac denervation in HTx recipients.
Cardiac denervation results in the inability to
suppress the renin–angiotensin–aldosterone
system (RAAS), thus leading to sodium and
water retention, which may be exacerbated
by corticosteroids. The expansion of circulating volume and hemodilution occurring during
pregnancy can further enhance the development
of hypertension [7, 62]. Physiologic pregnancy
is usually associated with estrogen-promoted
peripheral vasodilation and an increase in creatinine clearance, which may partially counterbalance this process [63]. However, hypertension
during pregnancy is commonly diagnosed
post-transplant in 25–48% of HTx recipients [5,
52]. Baseline hypertension in transplant recipi-
ents results in an increased risk of preeclampsia,
observed in 17–29% of HTx recipients [5, 52],
and preterm delivery [1]. To manage hypertension in these patients, one must consider the cardiovascular adaptation to hemodynamic changes
related to pregnancy, as well as the pharmacological interactions between anti-hypertensive
drugs and immunosuppression [14, 39, 64–66].
Meticulous control of blood pressure is advisable; generally nifedipine, amlodipine, labetalol,
hydralazine, and methyldopa can be used safely
in pregnancy (Table 27.5).
Infections
Infections, especially those of the urinary tract
and respiratory tract, can be more common in
pregnancy and should be actively screened for
and treated [7]. CMV infection is of particular concern in pregnant transplant recipients.
Primary CMV infection and reactivation are
common after transplantation, and during pregnancy, there are additional concerns about the
risk of congenital CMV disease in the fetus, a
potentially serious condition associated with
intellectual disability, microcephaly, and visual
or hearing loss [67]. The risk of transmission of
CMV to the fetus could be as high as 40% [67,
68] during primary infection, while for reactiva-
tion, the risk is lower [69]. As CMV carries a
significant risk to the fetus [70] as well as to the
transplant recipient, pregnant transplant recipients should be tested monthly for CMV viremia
during pregnancy. Patients who are CMVseronegative at the time of pregnancy should be
advised to adopt specific behaviors to minimize
the risk of primary infection. As CMV is often
transmitted through the care of young children,
regular hand washing, particularly after changing diapers, is recommended to decrease the
spread of infection and may reduce exposure to
CMV [71]. Maternal primary infection should
be treated to reduce the risk of vertical transmission, especially in the first trimester.

358 M. M. Kittleson
Immunosuppression During Pregnancy
Given the need to maintain adequate immunosuppression during pregnancy to prevent graft
rejection and loss, several important pharmacologic considerations must be considered in
the management of pregnancy after HTx. The
physiological changes observed during pregnancy can have a significant impact on the pharmacokinetics of immunosuppressants and other
agents critical to a transplant recipient’s medication regimen. The risks of fetal toxicities resulting from in utero medication exposure must be
weighed against the pregnant transplant recipient’s requirements. Many of these medications
also transfer into human milk, and the potential
for drug exposure to the infant via breastfeeding
should be considered. The efficacy and safety of
immunosuppression medications in pregnancy
and their use in breast feeding are summarized
in Table 27.6. Due to the inability to study the
safety of medication use during pregnancy and
lactation through robust, randomized controlled
trials, data to guide clinical decision-making are
limited to case reports and series. There is also
no international standard for risk assessment in
pregnancy and lactation in drug labeling.
The Transplant Pregnancy Registry
International is a critical source of information
regarding maternal and fetal outcomes of pregnant transplant recipients. As a voluntary registry, clinicians are strongly encouraged to enroll
pregnant patients to contribute to this body of
knowledge. Physiological changes affecting
pharmacokinetics during pregnancy can have
unpredictable effects on drug levels. Reduced
gastrointestinal motility, nausea and vomiting,
increased plasma volume and fat stores, changes
in plasma binding protein concentrations, and
drug metabolism can all impact immunosuppression levels [72–75]. While some studies
have described no change in immunosuppression levels during pregnancy, others report the
need for dosage escalation [21, 76, 77]. Due to
this unpredictability, therapeutic drug monitoring every 2–4 weeks with dose adjustment as
required to achieve target levels is advised during pregnancy [21, 77]. Frequent evaluation of
immunosuppression levels after delivery is also
essential as drug distribution and hepatic metabolism normalize in the postpartum period.
Postpartum Management
Given the increased risk of cardiovascular events
in the immediate postpartum period, postpartum
care in an intensive care unit setting is recommended, and early discharge from the hospital (<72 h) should be discouraged. Postpartum
thromboprophylaxis should follow local protocols. Postpartum monitoring of immunosuppression levels and for infection is critical. In
the general population, breastfeeding is associated with a myriad of immunologic, emotional,
and nutritional benefits. In HTx recipients, the
decision to breastfeed should be based on a
risk–benefit analysis of the potential for immunosuppressive medications to be excreted in the
breast milk. After 1–2 weeks of breastfeeding,
it is reasonable to check the infant’s serum for
measurable drug levels of cyclosporine or tacrolimus [78]. If significant levels are detected,
the mother may be counseled to discontinue
breastfeeding. Limited data are available regarding the excretion of mTOR inhibitors in breast
milk. Therefore, caution must be advised regarding breastfeeding in mothers taking mTOR
inhibitors. The Drugs and Lactation Database
(LactMed) and e-lactancia can be helpful
resources for physicians and patients when
determining which medications are safe for
breastfeeding mothers after HTx [79, 80].
References
1. Mastrobattista JM, Gomez-Lobo V. Pregnancy
after solid organ transplantation. Obstet Gynecol.
2008;112(4):919–32.
2. Kittleson MM, DeFilippis EM, Bhagra CJ, Casale
JP, Cauldwell M, Coscia LA, et al. Reproductive
health after thoracic transplantation: an ISHLT
expert consensus statement. J Heart Lung
Transplant. 2023;42(3):e1–42.
Соседние файлы в папке Библиотека им академика М.И. Перельмана
