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30 M. Hamilton and Y. Manla
Table 3.2 Recommended tests for initial evaluation of heart transplant candidacy
Recommended tests
• Weight/body mass index
• Immuno-compatibility
– ABO typing
– Human leukocyte antigen tissue typing
– Panel reactive antibodies and flow cytometry
• Assessment of severity of heart failure
– Cardiopulmonary exercise test
– Echocardiogram
– Right heart catheterization
• Evaluation of multi-organ function
– Routine laboratory work (basic metabolic profile, complete blood count, liver function tests)
– Urinalysis with toxicology screen
– 24-h urine collection for protein and creatinine
– Pulmonary function tests
– Chest radiograph
– Abdominal ultrasonography
– Carotid Doppler (if >50 years or with ischemic heart disease)
– Ankle-brachial indices (if >50 years or with ischemic heart disease)
– Dental examination
– Ophthalmologic examination (if diabetic)
– Chest and abdomen/pelvic CT scans (if indicated)
• Infectious serology and vaccination
– Hepatitis B surface, core, envelope antigen, antibody (IgG/IgM)
– Hepatitis C Ab
– Human immunodeficiency virus (HIV)
– Rapid plasma reagin
– Immunoglobulin G for herpes simplex virus
– Cytomegalovirus, toxoplasmosis, Epstein-Barr virus, varicella
– Purified protein derivative
– If from Latin American: Chagas screen
– Immunizations: influenza, pneumovax, hepatitis B, COVID
• Preventive and malignancy
– Stool for occult blood × 3
– Colonoscopy (if indicated or if >50 years)
– Mammography (if indicated or if >40 years)
– Papanicolaou smear test
– Prostate-specific antigen and digital rectal examination (men >50 years)
• General consultations
– Social assessment
– Psychiatry
– Financial
– As indicated: pulmonology, nephrology, infectious disease, endocrinology, hematology
Abbreviations: IgG: immunoglobulin G; IgM: immunoglobulin M
incorporated in the CPET test. Surpassing anaerobic threshold (AT) defines a maximal CPET
test from a cardiac standpoint. AT is defined
as the point during exercise at which oxygen
delivery to exercising muscles is insufficient
to sustain aerobic respiration, so anaerobic
pathways are predominantly utilized. Exercise
beyond this threshold, identified by respiratory
exchange ratio (RER) > 1.05, helps differentiate
true cardiac limitation from poor effort or potentially confounding pulmonary or musculoskeletal limitations. Ventilatory efficiency (VE/
V
) on CPET testing, defined as the ratio of
CO2
minute ventilation (VE) to the rate of carbon
dioxide production (V
), maybe a more pow-
CO2
erful prognostic factor than VO2max and is independent of body mass index [20, 21]. Stability
or improvement on serial CPET testing is also
313 Evaluation for Heart Transplant Candidacy
a useful finding for identifying patients who, in
conjunction with clinical stability, may be safely
removed from the transplant waiting list.
Models to Predict Survival in Advanced HF Patients
While certain measurements, such as LVEF,
are poor prognostic indicators by themselves,
the combination of multiple measures, including hemodynamics and peak VO2, can improve
prognostic value. Several broader models have
been developed to provide further predictive
value, but they are of variable use in individual
decision-making. Since 1- and 3-year transplant
survival is approximately 90% and 85% respectively, the ISHLT guidelines recommend HTx
only for patients with predicted survival on medical therapy significantly less than these values.
The HF Survival Score (HFSS) is a risk model
derived from a multivariable analysis of 268
ambulatory patients referred for consideration
of cardiac transplantation initially from 1986 to
1991 and subsequently validated in a population of 199 similar patients from 1993 to 1995,
with further modifications since then [22]. The
component predictors of survival in the HFSS
included the following: presence or absence of
coronary artery disease; resting heart rate; LVEF
by echocardiography; mean arterial blood pressure; presence or absence of an intraventricular
conduction delay on electrocardiogram; serum
sodium; and peak VO2 as determined by CPET.
Using this analysis, patients can be categorized
into low risk, with a one-year survival of 93%,
for whom transplant can generally be safely
deferred, or medium and high risk, with a 1-year
survival of 72% and 43%, respectively [22],
warranting consideration for HTx.
The Seattle HF Model (SHFM) is another
scoring tool derived from a cohort of 1125 HF
patients and subsequently validated in 9942
patients [12]. It is most useful for estimating the
prognosis of ambulatory patients with advanced
HF. The SHFM incorporates more clinical
and laboratory variables. Most pertinently, the
model is able to assess the impact of newer HF
therapies and devices (including implantable
cardioverter-defibrillators and cardiac resynchronization therapy) on predicted survival. The
primary limitation of the SHFM is that it was
derived from an ambulatory HF population and
thus may overestimate survival in the overall
advanced HF population [23, 24].
Psychosocial Evaluation
Psychosocial assessment should be performed
on all candidates prior to listing for transplantation to make sure they have the support, understanding, and commitment needed to have a
successful transplant. This involves compliance
with the complex medical regimen, as well as
the social support needed to assist with personal
care, meals, and transportation to follow-up
appointments or emergency care. This usually
requires both primary and secondary dedicated
caregivers. Isolated, stable cognitive impairment is not a contraindication to transplant if the
social support structure is strong, but dementia
would not be acceptable, owing to its progressive nature and overall poor prognosis.
Psychiatric evaluation should also be incorporated into the overall evaluation process for
HTx listing to identify any active psychiatric illness that may negatively affect adherence to care
regimens and would need to be stabilized and
monitored longitudinally before transplant listing. Since depression is common in HF patients
and can adversely affect post-transplant outcomes, it should be addressed and treated both
pre and post-transplant. Evaluation by palliative
or support care teams is required for consideration of durable mechanical support and should
be considered for transplant evaluations as well.
References
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JM, Mentz RJ, et al. Quantifying benefit-risk preferences for heart failure devices: a stated-preference
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2. Varshney AS, Berg DD, Zhou G, Sinnenberg L,
Hirji S, DeFilippis EM, et al. Bridging strategies and
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3. Peled Y, Ducharme A, Kittleson M, Bansal N,
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4. Barboza AB, Dhanani NH, Browning K, Wood RP,
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6. Hanke JS, Dogan G, Zoch A, Ricklefs M, Wert L,
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7. Velleca A, Shullo MA, Dhital K, Azeka E, Colvin
M, DePasquale E, et al. The International Society
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Heart Lung Transplant. 2023;42(5):e1-141.
8. Mehra MR, Kobashigawa J, Starling R, Russell S,
Uber PA, Parameshwar J, et al. Listing criteria for
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9. Miller LW, Kubo SH, Young JB, Stevenson LW,
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11. Keogh AM, Baron DW, Hickie JB. Prognostic
guides in patients with idiopathic or ischemic
dilated cardiomyopathy assessed for cardiac transplantation. Am J Cardiol. 1990;65(13):903–8.
12. Levy WC, Mozaffarian D, Linker DT, Sutradhar
SC, Anker SD, Cropp AB, et al. The Seattle heart
failure model: prediction of survival in heart failure.
Circulation. 2006;113(11):1424–33.
13. Rickenbacher PR, Trindade PT, Haywood GA,
Vagelos RH, Schroeder JS, Willson K, et al.
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14. Kittleson MM, Kobashigawa JA. Management of
advanced heart failure: the role of heart transplantation. Circulation. 2011;123(14):1569–74.
15. Mancini DM, Eisen H, Kussmaul W, Mull R,
Edmunds LH Jr, Wilson JR. Value of peak exercise
oxygen consumption for optimal timing of cardiac
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failure. Circulation. 1991;83(3):778–86.
16. Goda A, Lund LH, Mancini D. The Heart Failure
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21. Bard RL, Gillespie BW, Lange DC, Nicklas JM.
Improving prognostic assessment of patients with
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Goin JE, Mancini DM. Development and prospective validation of a clinical index to predict survival
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23. Gorodeski EZ, Chu EC, Chow CH, Levy WC, Hsich
E, Starling RC. Application of the Seattle heart
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24. Kalogeropoulos AP, Georgiopoulou VV, Giamouzis
G, Smith AL, Agha SA, Waheed S, et al. Utility
of the Seattle heart failure model in patients
with advanced heart failure. J Am Coll Cardiol.
2009;53(4):334–42.
Potential Contraindications to Heart Transplantation
Michelle M. Kittleson
4
Abstract
Heart Transplantation (HTx) is considered the gold standard for the treatment of
refractory end-stage heart failure. Due to
the scarcity of available donor hearts, careful evaluation for HTx candidacy is warranted. Thus, the goal of a HTx evaluation
is to determine if: the patient’s cardiac status
is limited enough, on optimal medical therapy, to benefit from HTx; the patient does
not have co-morbidities that would preclude
HTx; and the patient demonstrates compliance and possesses adequate social support.
Finding a balance between maximal individual survival benefit and maximal utility
will always remain a complex issue requiring
frequent reassessment. Ultimately, the decision to list a patient for transplantation is not
based on any one test or factor but acknowledges multiple factors, including indicators
for poor prognosis without transplant as well
as potential contraindications that may cause
suboptimal outcomes post-transplant. This
chapter will summarize the contraindications
to HTx as well as psychological and financial
considerations.
M. M. Kittleson (*)
Cedars-Sinai Smidt Heart Institute, Los Angeles,
CA, USA
e-mail: michelle.kittleson@cshs.org
Keywords
Heart failure · Heart transplantation ·
Contraindications · Evaluation ·
Psychological · Financial
Clinical Pearls
• Potential relative contraindications include
age > 70 years, obesity (BMI > 35 kg/m2),
pulmonary hypertension, primary pulmonary disease, poorly controlled diabetes
(HbA1C > 7.5%) or diabetes with end-organ
damage, renal dysfunction (eGFR < 30 ml/
min/1.73 m2), and any active infection
excluding left ventricular assist device
-related infections.
• Absolute contraindications include severe or
multiple of the above relative contraindication factors, metastatic malignancy, severe
cerebrovascular disease, strong indicators
for non-compliance, and a lack of social/caregiver support.
• Ultimately, the decision to list a patient for
transplantation is not based on any one test
or factor but acknowledges multiple factors,
including indicators for poor prognosis without transplant as well as potential contraindications that may cause suboptimal outcomes
post-transplant.
© 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_4
33
34 M. M. Kittleson
Introduction
Despite advances in pharmacological and device
treatment of chronic heart failure (HF), longterm morbidity and mortality remain unacceptably high; the 5-year mortality rate for patients
with symptomatic HF approaches 50% and
may be as high as 80% at 1 year for end-stage
patients [1]. For those patients in whom these
therapies (as detailed in Chaps. 1 and 2) have
been attempted without success, heart transplantation (HTx) may be a suitable option and
is considered the gold standard for the treatment of refractory end-stage HF. Evaluation for
transplant candidacy and transplant indications
have been described in Chap. 3. This chapter
will summarize the contraindications to HTx.
Due in part to the scarcity of available donor
hearts, careful evaluation for candidacy is warranted. Thus, the goal of a HTx evaluation is
to determine if: (1) the patient’s cardiac status
is limited enough, on optimal medical therapy,
to benefit from HTx (i.e., “sick enough”); (2)
the patient does not have co-morbidities that
would preclude HTx (i.e., “well enough”); and
(3) the patient demonstrates compliance and
possesses adequate social support (“can adapt
to a transplant lifestyle”). Finding a balance
between maximal individual survival benefit
and maximal utility will always remain a complex issue requiring frequent reassessment. A
limited number of established contraindications
are described in Table 4.1. Many of these factors
are not absolute and need to be considered in the
context of the severity of the patient’s heart disease and associated co-morbidities. The degree
to which they are interpreted and applied may
vary considerably among transplant programs.
A useful rule is that the presence of any
non-cardiac condition that would substantially
increase the peri- or postoperative risks of the
transplant or itself shorten life expectancy would
represent a medical contraindication. Similarly,
any psychosocial issues that would increase the
risk of death from rejection due to medical nonadherence would also place the patient at a prohibitively high risk for transplant.
Heart Transplant Contraindications
Age
As life expectancy continues to increase, traditional age limits for HTx may be expanded in
select cases. Generally, patients are considered
for HTx if they are 70 years of age or less, since
advances in post-transplant care have shown
that survival in the older age group is comparable to that of younger recipients [2]. Older age
does confer more risk of certain post-transplant
complications; compared to recipients under
the age of 60 years of age, older transplant
recipients have more infections, renal dysfunction, and malignancy, but less rejection [3, 4].
Increasing recipient age is associated with an
increase in post-transplant mortality, particularly
in patients aged ≥ 70 years at the time of trans-
plant, with the incidence of specific causes of
post-transplant mortality varying widely with
recipient age [3, 4]. Thus, patients over the age
of 70 years may have acceptable outcomes, but
careful consideration of associated co-morbidities is essential. At some centers, such patients
are offered nonstandard donor hearts, including those with coronary artery disease, mildly
decreased left ventricular ejection fraction, left
ventricular hypertrophy, or donor age older than
55 years old. This practice allows older patients
to undergo HTx without denying the scarce
resource to younger candidates, with comparable outcomes [5]. However, while older donors
may be considered for older HTx candidates,
this practice is of uncertain value given the
observation that older donors are associated with
worse post-transplant survival both in young and
old recipients [6]. This issue raises the ethical
question of using the scarce resource of young
donor hearts for older recipients, further exacerbated by the potential need for dual organ transplantation [7]. Physiologic age may be more
important than chronologic age with respect to
survival and rehabilitation potential. As a result,
many programs focus less on fixed upper age
limits and instead assess the patient’s functional
status, integrity of major organ systems, and the
4 Potential Contraindications to Heart Transplantation
Table 4.1 Summary of potential contraindications to cardiac transplantation
Potential contraindication Comments
Age
>70 years old is a relative contraindication depending on
associated comorbidities
Obesity
BMI < 35 kg/m2 is recommended
Malignancy Active or metastatic neoplasms are an absolute contrain-
dication
Pulmonary Hypertension
TPG > 15 mmHg, PVR > 5 Wood units or pulmonary
artery pressure > 60 mmHg with one of the above, or the
inability to achieve PVR < 2.5 Wood Units with vasodilator or inotropic therapy, are relative contraindications;
such patients may benefit from long-term unloading
with ventricular assist device followed by reassessment
Primary Pulmonary Disease In the presence of known primary lung disease, e.g.
emphysema or fibrosis, in combination with impaired
pulmonary function tests, defined as FEV
dicted, FVC < 50% of normal, DLCO < 40%, is a relative
< 40% of pre-
1
contraindication
Recent pulmonary embolism (within 6 weeks) is also a
contraindication
Diabetes Uncontrolled diabetes (HbA
mol) or diabetes with significant end-organ damage is a
> 7.5% or 58 mmol/
1C
relative contraindication
Renal dysfunction
eGFR < 30 is a relative contraindication
Hepatic dysfunction Cirrhosis with portal hypertension is a relative contrain-
dication
Peripheral vascular disease Severe disease not amenable to revascularization is an
absolute contraindication
Infection Active infections except LVAD-related infections are
contraindications; HIV, Hepatitis B and Hepatitis C are
not contraindications if not active and well-controlled by
treatment as defined by viral load/CD4 thresholds
Latent TB and Chagas are not contraindications
Substance use
6 months of abstinence from smoking, alcohol and illicit
drugs is required; in critically ill patients, consultation
with psychiatry and social work is essential. Marijuana
is a controversial topic
Psychosocial issues Non-compliance, lack of caregiver/social support, and
dementia are absolute contraindications; mental retardation may be a relative contraindication
35
BMI: body mass index; DLCO: lung diffusion capacity; eGFR: estimated glomerular filtration rate; FEV: forced
expiratory volume; FVC: forced vital capacity; HbA1C: glycosylated hemoglobin; HIV: human immunodeficiency
virus; LVAD: left ventricular assist device; mg: milligrams; mmol: millimoles; mol: moles; PVR: pulmonary vascular
resistance; TPG: transpulmonary gradient; TB: tuberculosis; dl: deciliters
36 M. M. Kittleson
presence of comorbidities that might impact survival, rehabilitation potential, and quality of life.
Obesity
Increasing rates of obesity are observed in the
HTx population, with a significant increase
in body mass index (BMI) over time [8].
Obesity with BMI ≥ 35 kg/m2 is associated
with increased waitlist time, increased waitlist
mortality, and increased post-mortality [9, 10].
There is a graded relationship between increased
BMI and worse post-transplant survival in multiple registries and meta-analyses, with the best
survival observed in those patients with normal
BMI but acceptable survival in those patients
with BMI 30–35 kg/m2 [11–14]. Considering
obesity is a potentially modifiable risk factor,
achieving a BMI under 35 kg/m2 is preferred to
optimize post-transplant quality of life and survival. For some patients, options including bariatric surgery may be considered, depending on
center expertise, resources, and patient stability
[15–17].
Malignancy
Malignancy after HTx remains a significant
cause of morbidity and mortality. All HTx candidates should be screened for breast, prostate,
and colon cancer as indicated and recommended
for the general population, as there is little data
to support malignancy screening recommendations specific to the HTx candidate [18]. Skin
cancer screening by full-body skin examination
completed by a dermatologist for all HTx candidates can be useful given the high prevalence
of skin cancer after HTx. For those HTx candidates with pre-transplant malignancies, collaboration with an oncologist is essential for an
individualized approach to risk stratification.
While a period of observation prior to transplant listing may be recommended, this will be
unique and specific to the given patient’s cancer history. An individualized approach with
multidisciplinary collaboration is essential, as
arbitrary time intervals for observation may
result in unnecessary delays in transplant listing.
Those candidates with low-risk pre-transplant
malignancy, including early-stage cancers with
full resection and/or low-risk features, including prostate adenocarcinoma, renal cell carcinoma, cervical cancer, and bladder cancer, may
undergo HTx with minimal or no pre-transplant
observation and plans for post-transplant intervention [19]. On the other hand, active and/
or metastatic neoplasms, with the exception of
non-melanoma skin cancer, are absolute contraindications to HTx, as the course of the tumor
may be accelerated by immunosuppression and
the utility of the donor heart would not be maximized. Further guidance is available in consensus statements from the American Society of
Transplantation with granular recommendations
on transplant candidacy in transplant candidates
with pre-transplant malignancies [19, 20].
Pulmonary Hypertension
Pulmonary hypertension (mean pulmonary
artery pressure > 20 mm Hg), most commonly
Group 2 due to left heart disease (pulmonary capillary wedge pressure > 15 mm Hg)
[21–23], is common in patients with HF [24,
25], and an elevated pulmonary vascular resist-
ance (PVR) ≥ 2.5 Wood units is associated with
increased early post-transplant mortality [26].
Although elevations in pulmonary artery systolic pressure (PASP), transpulmonary gradient (TPG), and pulmonary vascular resistance
(PVR) above certain thresholds have been proposed as contraindications to HTx listing, the
risk associated with each parameter is continuous from low to high values and absolute cutoffs do not exist [27, 28]. Even so, in patients
with PASP ≥ 50 mm Hg and either TPG ≥ 15 or
PVR ≥ 3 Wood units, a vasodilator (e.g., inhaled
nitric oxide or nitroprusside if nitric oxide is not
available) should be administered to document
an acute reduction in PVR to acceptable levels
[29]. An appropriate response to the vasodilator
challenge would be if the TPG can be reduced
to ≤ 12–15 mm Hg and the PVR to ≤ 2.5–3 WU.
4 Potential Contraindications to Heart Transplantation
37
If the PVR is reversible but systolic blood pressure falls to < 85 mm Hg with pharmacologic
maneuvers, the risk of right HF remains high
[29, 30]. When the response to the acute vasodilator challenge is not acceptable, hospitalization
with continuous vasoactive therapies and hemodynamic monitoring would be the next step in
management [31], followed by implantation of
temporary mechanical circulatory support or a
durable left ventricular assist device (LVAD) in
eligible candidates [32–38].
Primary Pulmonary Disease
Up to one‐third of unselected patients with HF
have concurrent chronic obstructive pulmonary disease (COPD), largely attributed to the
shared risk factor of smoking [39]. HF also
commonly co-exists with other lung diseases,
including interstitial lung disease [40]. Patients
with HF and lung disease have an increased
risk of longer post-transplant hospital stays and
increased mortality [41, 42]. Thus, it is essential
to screen HTx candidates for pulmonary parenchymal disease with pulmonary function testing, including spirometry, volume assessment,
and diffusion capacity, as well as chest imaging, most commonly non-contrast computed
tomography, to assess for parenchymal disease.
As pulmonary congestion may interfere with
the interpretation of these tests [43, 44], optimization of volume status with diuretic therapy
should occur prior to pulmonary evaluation.
Further testing may be required as dictated by
a pulmonary specialist. Patients with moderate
or severe airway obstruction (forced expiratory
volume in 1 s (FEV1) to forced vital capacity
(FVC) ratio < 0.7 and FEV1 < 80% predicted)
had higher operative mortality after cardiac
surgery, with the highest operative mortality in
those patients with diffusing capacity of the lung
for carbon monoxide < 50% of predicted [45]. In
HTx recipients in particular, FEV1 < 50% predicted and FVC < 50% predicted each was associated with significantly higher post-transplant
mortality, and these should be considered contraindications to transplantation in conjunction
with input from pulmonary consultants [41]. In
addition, chronic hypoxia requiring supplemental oxygen, attributable to a pulmonary source,
would contraindicate transplantation. A pulmonary embolism within the last 6 weeks also
serves as a contraindication to transplantation
because of the fear of recurrent emboli from
the original source and the potential for abscess
formation at the embolism site. Such patients
should be treated with anticoagulation and then
re-evaluated 4–6 weeks later with pulmonary
imaging to assess candidacy for listing.
Diabetes Mellitus
Approximately 30% of patients with advanced
HF and 20% of HTx recipients have preexisting diabetes [46, 47]. The presence of
uncomplicated post-transplant diabetes is not
associated with worse post-transplant survival
[47]. However, those HTx candidates with dia-
betes-related complications, including obesity,
kidney dysfunction, cerebrovascular disease, or
peripheral vascular disease, have worse posttransplant survival as well as an increased risk
of post-transplant infections and kidney failure in one registry analysis [47] and additional
risks of late graft failure and mortality in other
cohorts [48–53]. Therefore, diabetes per se is
not considered a contraindication for HTx, but
careful assessment of diabetic control and endorgan damage (atherosclerotic vascular disease,
nephropathy, proliferative retinopathy) is necessary. Posttransplant use of calcineurin inhibitors and corticosteroids will worsen glycemic
control [54], so pretransplant optimal control
to achieve glycosylated hemoglobin (Hgb A1c)
7–8% in collaboration with endocrinologists is
highly encouraged [55]. On a program-specific
basis, centers may identify a Hgb A1c level
that is considered a relative contraindication to
transplantation, especially in conjunction with
diabetes-related complications, which portend
worse post-transplant outcomes and because
poorly controlled diabetes may also be an indicator of suboptimal medical adherence in some
cases.
38 M. M. Kittleson
Renal Dysfunction
The goal of the pretransplant evaluation of kidney function is to differentiate chronic kidney
disease (CKD) that will not improve post-HTx
from acute kidney injury (AKI) or CKD, which
may reverse with the hemodynamic optimization afforded by HTx. This evaluation should
take into account (1) historical trends in kidney function during the months to years prior
to cardiac decompensation, (2) current trends
in kidney function when the patient is hemodynamically optimized, ideally over a few weeks
duration, (3) comorbidities (e.g., diabetes, lupus)
known to be associated with irreversible kidney
damage (4), and other findings like the presence of proteinuria [56]. Transplant candidates
should have two independent measurements for
GFR at least 2 weeks apart using serum creatinine measurements and race-free equations for
eGFR [57–59]. The confirmatory GFR measurement should be a measured GFR, such as
24-h creatinine clearance [60]. The results of
ancillary testing may be used to assess for the
presence, severity, and chronicity of intrinsic
renal disease, including the presence of cortical scarring on renal ultrasound or proteinuria.
A kidney biopsy is rarely required. While worse
renal function pre- and post-HTx portends worse
outcomes post-HTx [2, 61, 62], data demonstrating improved survival with simultaneous
heart-kidney transplant versus HTx when pretransplant GFR is below a specific threshold are
limited [63–66]. A UNOS registry analysis of
over 13,000 recipients transplanted 2005–2018
determined that transplant recipients derived
increased survival for simultaneous heart-kidney
transplant vs. HTx if they had eGFR < 45 ml/
min/1.73 m2 though kidney graft survival was
lower in patients after simultaneous heart-kidney
transplant than kidney transplant alone (1-year
graft loss 14.7% vs 4.5%) [67]. Another challenge is marked changes in kidney function in
HTx candidates while on the waiting list. In situations where there is inadequate time to assess
for AKI recovery, both heart and kidney specialists should weigh all factors (i.e., perceived
kidney reserve and recovery potential, risk or
presence of CKD) in order to decide simultaneous kidney and HTx vs HTx candidacy. A caveat
to qualify for simultaneous kidney with HTx
is that the patient must have evidence for CKD
(eGFR < 60 ml/min/m2 at 90 days apart. This
policy was initiated as patients with AKI without CKD are mostly able to have kidney recovery after HTx. If patients with eGFR < 30 ml/
min/m2 are deemed ineligible for kidney transplantation, HTx alone should generally not be
pursued, given worse outcomes in recipients of
HTx alone compared with simultaneous kidney and HTx when eGFR < 30 ml/min/m2 [67].
Collaboration with nephrologists is essential
for optimal donor stewardship. In the United
States, a Safety Net approach has been proposed to theoretically allow better prioritization
of donor organs. In this policy, HTx recipients
would qualify for the Safety Net kidney donor
if they were (1) registered on the kidney waiting list prior to the one-year anniversary of their
HTx and (2) were on chronic dialysis or had a
measured or estimated creatinine clearance or
GFR ≤ 20 ml/min/1.73 m2 between day 60 to
day 365 posttransplant [68]. Some critically ill
HTx recipients face a high rate of renal allograft
dysfunction due to peri-operative hemodynamic
instability and may benefit from this option,
assuming a living donor is not available.
Hepatic Dysfunction
Patients with severe heart disease may have
co-existing liver disease from various causes.
Patients with advanced HF and chronic liver
disease who undergo HTx alone have reduced
survival compared to those without liver disease
[69]. Irreversible hepatic cirrhosis can significantly increase the risks of a HTx and is usually
considered an absolute contraindication unless a
combined heart and liver transplant (CHLT) can
be performed [70].
CHLT is increasingly offered as an option
for such patients. In recent years, approximately
40–50 CHLT surgeries have been performed
4 Potential Contraindications to Heart Transplantation
39
annually in 25 centers in the United States. The
most common indications for liver transplant
in CHLT include non-congenital heart disease
with non-cardiac cirrhosis (e.g., hepatitis C virus
(HCV), alcohol-associated cirrhosis), congenital
heart disease (CHD) with congestive hepatopathy and variant transthyretin cardiac amyloidosis (though less common in the current era
due to the advent of effective disease-directed
therapies).
A meta-analysis found that a CHLT is a safe
and effective procedure for managing progressive heart and/or liver failure [71]. This metaanalysis included 16 studies with 860 patients.
The mortality rate following CHLT was 14.1%.
One and five-year survival rates were 85.3 and
71.4%, while the heart and liver rejection rates
were 6.1 and 9.1%, respectively. The hospital
stay was 25.8 days, and the intensive care unit
stay was 9.9 days. These results are comparable
to heart-alone transplantation. The authors note
that CHLT is a complex procedure that requires
expert surgeons, multidisciplinary consultation,
and advanced immunology and critical care
knowledge.
Liver cirrhosis is generally considered a contraindication to a HTx. However, some studies suggest that patients with end-stage HTx
and liver cirrhosis may be eligible for a HTx
if cases are carefully selected [72]. However,
liver cirrhosis has been linked to poor outcomes
after a HTx, and one study found that liver cirrhosis with moderate to severe ascites can lead
to worse overall survival for up to two years
after the transplant [73
]. In that study, between
1994 and 2018, 170 patients with advanced HTx
underwent HTx. Abdominal sonography or CT
was performed to assess ascites in 163 patients
preoperatively. Among them, 49 patients
(30.0%) had visualized ascites and enrolled in
this study. These patients were divided into two
groups [group A; mild ascites (n = 35), B; mod-
erate to massive ascites (n = 14)] and compared
the clinical outcomes. The 1, 2, 5 and 10-year
survival rates were 82.8 versus 74.3%, 78.4 versus 74.3%, 74.6 versus 74.3% and 74.6 versus
74.3%, respectively, and the survival rates were
significantly lower until 2 years in group B than
A (p = 0.035). However, there was no difference
after 2 years (p = 0.793). Cox-regression analy-
sis showed a moderate to massive ascites was
associated with an increased risk of all-cause
death after transplantation (p < 0.001).
The decision of when liver transplantation
is warranted in a patient with advanced HF
and compensated chronic liver disease is challenged by difficulties in differentiating those
patients with moderate hepatic fibrosis (which
may be reversible) from those with advanced
fibrosis and/or cirrhosis who could benefit from
this intervention. This can be particularly challenging given the overlap in clinical symptoms
in advanced cardiac and liver disease and the
lack of rigorous data for CHLT. Dedicated liver
imaging should be performed for HTx candidates with the presence or prior history of liver
disease or greater than 10 years of cardiac disease. If the liver appears potentially cirrhotic
(nodular) on imaging, then liver transplant
evaluation should be pursued. In this situation,
participants in a consensus conference on heartliver transplantation agreed that a liver biopsy
should be performed when technically feasible
and acceptably safe [74]. A liver biopsy may not
be required if there are stigmata of portal hypertension (e.g., varices, ascites). In the presence
of ascites, it is important to perform diagnostic
paracentesis to determine the cause of ascites
(hepatic or cardiac). Isolated hepatic venous
pressure gradient (HVPG) should not be used to
rule in or rule out portal hypertension, especially
in patients with Fontan-associated liver disease
(FALD), as it may not be reliable. If crosssectional imaging reveals portosystemic collaterals, upper endoscopy should be performed
for variceal screening and the need for primary
prophylaxis. In lower-risk patients (those with
compensated HF), a normal elastography result
(consistent with a liver biopsy of F0/F1) can be
used to exclude advanced liver disease.
Biopsy-proven cirrhosis, regardless of the
presence of portal hypertension, is generally
considered a contraindication for HT alone.
Biopsy-proven stage 3 fibrosis (F3) and/or clinical evidence of portal hypertension should be
a barrier to HT alone. The CHLT rate for adult