International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449

Contents lists available at ScienceDirect

International Journal of Cardiology

Congenital Heart Disease
journal homepage: www.journals.elsevier.com/international-
journal-of-cardiology-congenital-heart-disease

Nutrition, dietary recommendations, and supplements for patients with

congenital heart disease
Macarena Lorente a, María Josefa Azpiroz a, *, Paula Guedes b, Rosa Burgos c, Amador Lluch c,
Laura Dos a, d, e
a
Adult Congenital Heart Disease Unit. Cardiology Department. Vall d’Hebron University Hospital, Barcelona, Spain
b
Adult Congenital Heart Disease Unit. Cardiology Department. Canary Island University Hospital. Tenerife. Spain
c
Nutrition Support Unit, Endocrinology and Nutrition Department, Vall d’Hebron University Hospital. Spain
d
Vall d’Hebron Institut de Recerca (VHIR), Barcelona. Spain
e
CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III. Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Nutrition is the cornerstone of a healthy life and is crucial for the prevention of cardiovascular disease. Patients
Congenital heart disease with congenital heart disease (CHD) are prone to nutrition disorders, including abnormalities in body compo­
Nutrition sition such as overweight or obesity which, along with other classic cardiovascular risk factors, places our
Dietary recomendation
increasing and aging adult CHD (ACHD) population at a higher risk for acquired cardiovascular disease. These
Cardiovascular risk prevention
Iron status in cyanotic congenital heart disease
patients are also at risk of cachexia or sarcopenia as well as macronutrient and micronutrient deficiencies derived
from the development of heart failure as a complication of their underlying cardiac disease. In this paper, we
review different dietary recommendations and supplementation with specific macronutrients and micro­
nutrients. We also discuss some special scenarios in ACHD patients and the importance of the microbiota, a new
therapeutical target as yet underexplored in this patient population.

1. Introduction
Healthy habits are crucial for the prevention of cardiovascular dis­
ease (CVD). Nutrition, together with regular exercise, smoking cessa­
tion, and appropriate rest, among others, is the cornerstone of a healthy
life. Indeed, there is strong evidence supporting the association between
diet and increased risk of CVD and it has been estimated that nutritional
factors are responsible for about 40% of all CVD [1]. Unhealthy dietary
patterns (i.e., excessive intake of sodium and processed foods; added
sugars; unhealthy fats) predominant in Western countries, as opposed to
healthier dietary patterns (favouring intake of fruit, fibre, vegetables,
whole grains, fish, legumes, and nuts) such as the Mediterranean diet,
lead to a proinflammatory state responsible for the development of
atheromatosis [2].
If dietary habits are important for disease prevention, once heart
disease is established, either due to acquired or congenital conditions,
nutrition becomes paramount. Interestingly, nutrition disorders,
including abnormalities in body composition such as obesity, cachexia
or sarcopenia, and/or macronutrient and micronutrient deficiencies, are
highly prevalent in cardiac patients, predominantly in those afflicted
with heart failure (HF), the leading cause of morbidity and mortality in
ACHD [3]. In fact, malnutrition (defined as deficiencies or excesses in
nutrient intake, imbalance of essential nutrients, or impaired nutrient
utilisation) is independently associated with an increased risk of major
cardiovascular events in ACHD patients [4].
Sarcopenia is defined as a progressive and generalised disease of
skeletal muscle, characterised by a decrease in muscle strength and
mass, and is frequently associated with advanced stages of HF [5]. In
addition to sarcopenia, the definition of sarcopenic obesity requires the
presence of excess adiposity [6].
The terms sarcopenia and cachexia are often used interchangeably;
however, they correspond to different body composition phenotypes.
Cachexia is defined as an unintentional, non-edematous weight loss of
5–6% in the last 12 months. Cachexia typically shows a decrease in fat
mass, in contrast to sarcopenia and sarcopenic obesity, in which loss of
lean mass is accompanied by preservation of, or even an increase in, fat
mass. Cachexia is associated with anorexia as well as progressive
worsening of functional capacity [7].
On the other hand, obesity is a well-known cardiovascular risk factor
and an independent risk factor for HF. Recent evidence has shown that

* Corresponding author.
E-mail address: jazpirozfranch@gmail.com (M.J. Azpiroz).

https://doi.org/10.1016/j.ijcchd.2023.100449
Received 31 January 2023; Received in revised form 3 March 2023; Accepted 12 March 2023
Available online 17 March 2023
2666-6685/© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
M. Lorente et al.
metabolic syndrome is more prevalent in ACHD than in the general
population, and its prevalence increases with age [8]. Considering an
increasingly large and aging ACHD population, with high rates of
overweight and obesity [4], it is of vital importance to emphasise a
broader assessment of health behaviours and healthy habits.
Regarding the assessment of the patient’s nutritional status, several
methods have been used, the most common tool in clinical practice
being the body mass index (BMI). While it is easy to use, it does not
differentiate weight due to excess fluid or lean mass. However, lower
BMI values are associated with worse prognosis, particularly in symp­
tomatic patients with complex CHD [9]. Conversely, the methods that
measure body composition allow us to differentiate the proportion of fat,
lean, and liquid mass. However, some methods are inaccurate in the case
of excess body water (dual-energy X-ray absorptiometry or bioelectrical
impedance analysis), while other methods are expensive and/or
impractical (magnetic resonance imaging) [7]. The use of opportunistic
CT scans to evaluate muscle mass could help to evaluate sarcopenia in
patients with heart disease [10]. Biomarkers such as albumin, pre­
albumin, and lymphocyte count have been reported as indicators of poor
nutritional prognosis in patients with HF; although simple to measure,
they can be affected by comorbidities, medications, and inflammation
[11].
Finally, multidimensional assessment tools incorporate several do­
mains to categorise the severity of malnutrition in the context of HF. The
nutritional risk index (NRI) combines serum albumin levels and weight
loss and has been validated in many populations of patients with ac­
quired heart disease, being a better predictor of survival than albumin or
BMI alone [12]. A low NRI has been shown to be an independent pre­
dictor of cardiovascular event in CHD patients [4]. These scores have
been extensively validated, however, there is no accepted reference tool
and their results may reflect the severity of the patient’s underlying
disease rather than malnutrition.
Beyond detecting patients with stablished nutritional deficits, it is
important to detect population at risk. Such assessment should include
medical history, current and past dietary intake (including energy and
protein balance), physical examination and anthropometric measure­
ments, functional and mental assessment, quality of life, medications,
and laboratory parametres. Futhermore, some Nutritional Scores have
been developed to detect peadiatric patients at risk of nutritional dis­
orders. According to a systematic review [13] at least 33 different
nutritional risk screening tools exist, for use in various clinical settings
and patient populations (inpatients, community, geriatrics, etc.). The
European Society for Clinical Nutrition and Metabolism (ESPEN) rec­
ommends specially three of them: the Nutritional Risk Screening 2002
(NRS-2002) for the inpatient setting, the Malnutrition Universal
Screening Tool (MUST) for the ambulatory setting and the Mini Nutri­
tional Assessment (MNA) for institutionalized geriatric patients [14]. So
far, there are no specific tools developed for the setting of CHD patients.
In this paper, we review different dietary recommendations and
supplementation with specific macronutrients and micronutrients. We
also discuss some special scenarios in CHD patients (see Table 1) and the
importance of microbiota. We will focus on the CHD literature available
but, for those topics in which the evidence for CHD is scarce or absent,
we will mainly refer to the literature regarding the HF population as it is
the main driver of morbidity and mortality in ACHD. CHD patients are at
a higher risk of developing classic cardiovascular risk factors, such as
overweight and obesity, metabolic syndrome, hypertension,
Table 1
Nutritional disorders associated to specific congenital heart defects
Specific congenital heart disease Nutritional deficit
Cyanotic CHD Iron deficiency
Fontan circulation Protein-losing enteropathy
Failing systemic right ventricle Malnutrition, sarcopenia, cachexia
Tetralogy of Fallot Dysbacteriosis
2
International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449
dyslipidaemia, and diabetes mellitus. Thus, it is expected that dietary
interventions with a proven lowering of the cardiovascular risk profile
and risk factors, will be particularly beneficial in this population.
2. Dietary recommendations
The importance of a patient’s nutritional status for a complete
medical assessment has been increasing during the last few years. ESC
Guidelines offer dietary advice for the prevention of CVD in the general
population. However, when it comes to specific patient groups, dietary
recommendations are scarce and weak. As an example, although some
dietary interventional trials have already been undertaken, the current
HF guidelines offer only short recommendations on nutrition, mainly
derived from expert opinion consensus.
2.1. Nutritional restrictions
Dietary recommendations in HF are so uncertain that even the
worldwide strategy of dietary sodium restriction is not exempt from
controversy. It reduces congestive symptoms and improves functional
class; however, some studies have reported neurohormonal activation in
response to sodium restriction with renin-angiotensin-aldosterone sys­
tem activation and worsening renal function. A low-sodium diet (<1500
mg daily), in the recently published SODIUM-HF trial, was associated
with a better quality of life and functional status with no significant
improvement in outcomes [15].
The same applies to the body weight control recommendation. The
main HF guidelines recommend intentional weight reduction to
decrease adiposity to lower the risk of incident HF and increase peak
oxygen consumption. However, numerous studies have reported the
obesity paradox, in which a protective effect of class I or II obesity on the
survival of patients with established HF was found. The exact mecha­
nisms are not well established yet but an underlying metabolic reserve
and increased muscle mass have been suggested.
2.2. Dietary patterns
The Mediterranean (MedDiet) and the DASH (Dietary Approaches to
Stop Hypertension) diets are the most frequently studied patterns for
CVD risk reduction. Both share many common characteristics, encour­
aging the consumption of fruit, vegetables, whole grains, and legumes.
While the DASH diet limits sodium, saturated fatty acids, and total fat
intake, the MedDiet emphasises unsaturated fatty acids (Fig. 1A and B).
The PREDIMED clinical trial [16] showed a lower incidence of
myocardial infarction, stroke, or cardiovascular death in participants
randomised to MedDiet. Ensuing large observational trials have
demonstrated a reduction in HF incidence, as well as improvement in
clinical outcomes in patients with existing HF adhering to a MedDiet.
The main benefit of this diet against CVD is mainly derived from the
improvement of risk factors: blood pressure, lipid profile, glucose
metabolism, arrhythmic risk, or gut microbiome. Additionally, it was
suggested that the MedDiet has an anti-inflammatory effect with a
reduction in adiposity, C-reactive protein, insulin resistance, and
interleukin-6 (components associated with a higher likelihood of CVD)
[17]. However, the scarce evidence concerning CHD shows a low
adherence of our patient population to this diet [18].
On the other hand, the DASH study reported that a dietary pattern
with fruit, vegetables, low-fat dairy, low saturated fat, total fat, and
cholesterol, reduced systolic and diastolic blood pressure. The DASH
diet provides a complex mixture of nutrients, low in sodium and high in
potassium with evidence supporting an improvement in cardiac func­
tion, functional capacity, blood pressure, oxidative stress, and mortality
[19].
Fasting has increased in popularity over the past decade and is
commonly used worldwide at different intervals and for different rea­
sons, such as religion or health. Intermittent fasting is reported to have
M. Lorente et al.
various beneficial effects on health, such as regression of obesity and
insulin resistance, leading to overall improvement of cardiovascular risk
factors. There are different fasting patterns: alternate-day fasting implies
alternate days of ≤25% intake of baseline energy needs with days of ad
libitum food consumption, whereas periodic fasting subjects only fast for 1
or 2 days a week. However, as a strategy to maintain body weight and
optimal cardiometabolic health, it appears less effective than simple
caloric restriction. This is due to the difficulty in sustaining such re­
gimes, which also limits the development of large studies with quality
data to assess the long-term effects of intermittent fasting. A Cochrane
review [20] published in 2019 concluded that, compared to ad libitum
feeding, intermittent fasting produces weight loss of 3–8% over the
course of 3–24 weeks, but without any clinical impact, probably due to
the short-term follow-up.
Regarding HF, a recently published study [21] found an association
between regular periodic fasting and a reduction in all-cause mortality
and the incidence of HF. However, for those patients in advanced HF
with a fragile fluid balance, fasting should be discouraged. Indeed, the
recommendations published in 2020 by the British Islamic Medical As­
sociation advised against fasting for patients with advanced HF and
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International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449
Fig. 1. Comparison between the Mediterranean and
the Dietary Approaches to Stop Hypertension (DASH)
diets.A. Mediterranean diet: is based on the diary
intake of vegetables, whole grain, fruits and beans.
Animal origin protein is recommended once a day,
mainly fish and seafood, also eggs and dairy products;
while low consumption of red meat is recommended.
The Mediterranean diet emphasises the consumption
of unsaturated fatty acids, being olive oil the main
source of fat in the diet.B. Dietary Approaches to Stop
Hypertension (DASH) diet: it is also based on fruits,
vegetable and whole grain and cereal, recommending
higher intake of fish and white meat, and lower
intake of low-fat dairy products. Low consumption of
red meat and sweets is also recommended. DASH diet
limits sodium, saturated fatty acids, and total fat
intake. (For interpretation of the references to colour
in this figure legend, the reader is referred to the Web
version of this article.)
those with severe pulmonary hypertension [22]. There is no specific
recommendation for CHD patients, just emphasising a referral to the
CHD specialist for an individualised decision. This individualised
recommendation should take into consideration the unique fluid bal­
ance of certain CHDs, such as cyanotic or Fontan patients, for example.
The ketogenic diet (KD) is of particular interest in HF (Fig. 2). The
failing heart progressively loses its capacity to oxidise free fatty acids
(FA) and glucose switches the energy supply toward ketone body (KB)
substrates (Fig. 2). Experimental studies suggested that the provision of
KBs to the failing heart may have salutary effects by improving cardiac
efficiency [23]. Ketosis can be achieved by prolonged fasting, a KD, or
exogenous ketone administration. The KD is defined by a high intake of
long-chain FAs (55%–75% of daily caloric intake) and decreasing car­
bohydrate intake (5%–10% of daily caloric intake). However, chronic
exposure to a KD is not exempt from concerns as it increases low-density
lipoprotein cholesterol, thus increasing atherosclerotic CVD. On the
other hand, KD reduces peripheral glycogen stores, a strong determinant
of exercise capacity.
M. Lorente et al.
Fig. 2. The ketogenic diet: The KD is defined by a high intake of long-chain FAs (55%–75% of daily caloric intake) and decreasing carbohydrate intake (5%–10% of
daily caloric intake). The low carbohydrate intake induces the hepatic synthesis of ketone bodies, which are a source of energy.
3. Dietary supplements
There are several studies focusing on the role of dietary supplements
in cardiovascular health, both in the setting of secondary and primary
prevention. However, the conflicting nature of the results precludes
strong recommendations for the general population and particularly in
patients with CVD. In the field of CHD, the evidence is scarce, and most
recommendations are extrapolated from studies in patients with ac­
quired heart diseases. Only a few interventions in specific scenarios have
demonstrated an improvement in cardiovascular health.
3.1. Micronutrient supplementation
Micronutrient deficiency is relatively common in patients with heart
disease, particularly in those afflicted with HF. It is associated with poor
clinical status and correction of these deficiencies has been shown to
improve physical performance and quality of life [24].
Concerning minerals, coenzyme Q is known to have antioxidant
activity and its deficiency has been associated with worse cardiac
function in HF. However, a recent meta-analysis concluded that there
was no convincing evidence to support or refute the use of coenzyme
Q10 for HF due to the limited quality of the data available from pub­
lished studies [25]. Supplementation with magnesium or other
commonly deficient minerals in HF, such as zinc, calcium, and folate,
has also failed to improve cardiovascular outcomes [26].
Interest in the potential benefits of vitamin supplementation is sup­
ported by basic research and biological evidence regarding their ca­
pacity to decrease thrombogenesis, the inflammatory profile, and
improve endothelial function [27]. Severe thiamine (vitamin B1) defi­
ciency can lead to reversible cardiomyopathy, and less severe deficits
are common in HF, related to diuretic use. Small trials suggested that the
thiamine supplementation could improve ejection fraction and HF
symptoms [28]. L-carnitine is a key cofactor for myocardial energy
production, and essential for decreasing the pathological accumulation
of long-chain fatty acids that occurs during myocardial ischemia. Small
trials suggested that administration of L-carnitine in the setting of
myocardial infarction provides an antiarrhythmic effect and reduces
ventricular volumes. A recent meta-analysis in the setting of chronic HF
suggested beneficial effects of L-carnitine on symptoms and cardiac
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International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449
function [29].
On the other hand, trials on supplementation with vitamins B6, B12,
and C failed to show any beneficial effects [26]. Furthermore, vitamin D
supplementation may have deleterious effects by a reduction in the
6-min walk test distance and worsening of HF symptoms. In turn,
vitamin E supplementation has been associated with an increased inci­
dence of HF hospitalization [27].
As for primary prevention, a recent meta-analysis of clinical trials
and prospective cohort studies demonstrated that multivitamin and
mineral supplementation does not prevent CVD in the general popula­
tion [30].
While the normalisation of micronutrient deficiencies in CVD,
particularly in the HF population, seems to have a positive impact on the
overall patient status, there is no strong evidence supporting the benefits
of multivitamin and mineral supplementation in the general population.
3.2. Macronutrient supplementation
Polyunsaturated fatty acid (PUFA) supplementation through dietary
sources, such as extra-virgin olive oil, fish, and nuts, was proven to
improve cardiovascular outcomes within a Mediterranean diet [14]. In
the IMPROVE-IT trial, supplementation with icosapent ethyl twice a day
reduced the risk of cardiovascular ischaemic events (including cardio­
vascular death) compared to placebo in a cohort of patients with high
cholesterol levels despite the use of statins [31]. In general population, a
low ratio between levels of eicosapentaenoic acid and those of arach­
idonic acid (EPA/AA) has been associated with higher incidence of
coronary artery disease, heart failure and cardiac sudden death. A recent
in a congenital heart disease population, low EPA/AA was associated to
a higher risk of heart failure hospitalization [32], suggesting that eico­
sapentaenoic supplementation coulg be beneficial in this population. A
more recent metanalysis, including 13 randomised control trials, marine
omega-3 supplementation was associated with significantly lower of
cardiovascular events such as myocardial infarction as well as a reduc­
tion in cardiovascular death, in a dose-dependent relationships, even
after exclusion of REDUCE-IT [29]. Based on these results, the European
Society of Cardiology recommends n-3 PUFAs in high risk patients with
high triglycerides despite lifestyle measures and statin treatment (with a
class IIb recommendation). However, studies are very heterogeneous,
M. Lorente et al. International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449

and results are inconsistent, thus more evidence is needed in primary fumarate was used and titrated to a maximum dose of 200 mg thrice
prevention. daily [37]. In a more recent study in a larger cohort of patients, intra­
venous iron carboxymaltose (500–1000 mg) appeared to be safe for
treating iron deficiency in cyanotic patients with CHD and/or pulmo­
3.3. Iron supplementation in HF and cyanotic CHD
nary hypertension. Iron deficiency was defined as ferritin concentration
<30 μg/L or transferrin saturation <20%. A significant increase in
Cyanotic CHD encompasses a heterogeneous group of lesions with
ferritin, transferrin saturation, and haemoglobin concentration was
different underlying anatomies and pathophysiology. These patients
observed in all subgroups, with no cases of excessive erythropoiesis
must generate different compensatory mechanisms to adapt to the low
resulting in new hyperviscosity symptoms [38]. There are no clear
oxygen tension and low oxyhaemoglobin saturations. Secondary eryth­
recommendations on how to supplement iron in cyanotic patients,
rocytosis develops to improve oxygen supply to peripheral tissues [33].
including the choice between intravenous and oral therapy, dose, and
Sufficient iron stores are required to achieve and maintain adequate
treatment target [39], however, a low dose of oral elemental iron (100
haemoglobin levels. On the other hand, hypoxia-inducible factor (HIF)
mg/day) is usually well tolerated and will suffice in the majority of
activity, a key determinant of the adaptation to chronic hypoxia, is both
cases, reserving the option of intravenous administration for those pa­
regulated by iron and HIF itself regulates aspects of iron homeostatic
tients intolerant to oral presentations (Fig. 3). For patients in HF, it is
control [34].
advisable that iron reposition follows the current recommendations
Unfortunately, iron deficiency is a relatively common finding in
[39], although no evidence supports this strategy in cyanotic patients.
cyanotic patients and is associated with adverse late outcomes [35]. Iron
deficiency causes a reduction in haemoglobin without a proportional
4. Special scenarios
change in haematocrit and, thus, compromises systemic oxygen trans­
port without reducing viscosity [33]. Assessment of serum iron, ferritin,
4.1. Protein-losing enteropathy
and transferrin levels is required for the earlier detection of iron defi­
ciency [36].
Protein-Losing Enteropathy (PLE) is defined as the abnormal loss of
An uncontrolled prospective study, in a small cohort of patients,
serum proteins into the intestinal lumen due to a loss of wall perme­
showed that replenishment of iron stores in iron-deficient cyanotic CHD
ability. PLE can complicate the course of different types of CHD, but it is
patients was safe and resulted in improved quality of life and exercise
characteristically associated with failure of the Fontan circulation and is
capacity, regardless of baseline haemoglobin levels. Iron deficiency was
expected to occur in 5%–12% of these patients. The importance of early
defined as serum ferritin <30 μg/L or serum ferritin <50 μg/L and
diagnosis and treatment of this complication lies in the associated high
transferrin saturation <15%. For iron supplementation, oral ferrous

Fig. 3. Iron status assessment and supplementation in cyanotic patients. Regarding that evidence is scarce, studies are heterogenic and Clinical Guidelines do not
provide a concise strategy for iron supplementation, we propose an algorithm for iron status assessment and supplementation in cyanotic patients. Proposed cut-off
values are based on the only study evaluating i. v. iron supplementation in cyanotic congenital heart disease or pulmonary hypertension [35].*TSI: transferrin
saturation index.

5
M. Lorente et al.
morbidity and mortality [40].
The gold standard for the diagnosis of PLE is faecal alfa-1-antitrypsin
(α1-AT). An elevated level of α1-AT in a single stool sample, along with
an unexplained presence of serum hypoalbuminemia and peripheral
oedema, are necessary requisites for diagnosis.
The therapeutic approach towards PLE involves diuretics, albumin
replacement, intravenous immunoglobulin administration, angiotensin-
converting enzyme inhibitors, heparin, corticosteroids, or pulmonary
vasodilators, as well as invasive treatment with transcatheter or surgical
techniques. However, nutritional support is crucial since all patients
afflicted with PLE are malnourished. Patients loose calories due to
protein loss, associated fatty diarrhoea, and difficulty absorbing long-
chain triglycerides through the intestinal lymphatic system.
Dietary recommendations are based on a high-protein intake (2 g/
kg/day), usually by adding protein supplements, low-fat diet (≤25% of
calories from fat) with a higher proportion of medium-chain tri­
glycerides. Medium-chain triglyceride supplements are absorbed
directly into the bloodstream, bypassing the damaged lymphatic system
[41].
There are no controlled studies supporting the efficacy of this diet;
dietary intervention alone has rarely produced clinical improvement.
However, enhancing nutritional status by increasing effective caloric
intake is crucial, considering the chronic hypercatabolic state of the PLE
patient and the indolent course of the disease compromising growth,
wound healing, immune response, coagulation, and bone metabolism.
4.2. Nutritional prehabilitation in CHD surgery
It is strongly recommended that patients eligible for cardiac surgery
undergo perioperative nutritional screening and stratification of their
surgical risk by measuring HbA1c, to optimise glycaemic controls, and
serum albumin. This risk assessment allows the identification of patients
that may benefit from perioperative nutritional support. Poor preoper­
ative nutritional status is associated with increased muscle wasting and
is a predictor of delayed functional recovery after cardiac surgery.
Furthermore, malnutrition has been found associated with prolonged
ICU stay and is an independent risk factor for postoperative complica­
tions [42]. Likewise, cardiac surgery may cause further deterioration of
nutritional status due to postoperative catabolic reaction and decreased
dietary intake [43].
Concerning CHD, several studies have addressed the importance of
preoperative nutritional status in children, suggesting that lower total
body fat mass and acute and chronic malnourishment are associated
with worse clinical outcomes [44]. However, no specific studies in the
adult CHD population undergoing cardiac surgery have been
undertaken.
To achieve the greatest benefit, preoperative nutritional support
should be initiated at least 2–7 days prior to surgery, in a pre-admission
setting. There are several scoring systems to evaluate patients’ preop­
erative nutritional status [45], however, there is no current evidence
supporting that nutritional therapy would improve postoperative out­
comes [46].
As important components of all Enhanced Recovery After Surgery
(ERAS) protocols, several randomised clinical trials have demonstrated
that non-alcoholic clear fluids can be safely given up to 2 h before the
induction of anaesthesia, and a light meal can be given up to 6 h before
elective procedures requiring general anaesthesia [47].
Postoperative nutritional support should be initiated early in pa­
tients with high nutritional risk and expected prolonged ICU stay (0–24
h after surgery), favouring enteral nutrition whenever possible [46].
Finally, supplementation of fish oil emulsions appears to have a
benefit in modulating the inflammatory response occurring in the
context of cardiac surgery, especially in patients undergoing complex
procedures with longer cardiopulmonary bypass times. In addition,
these emulsions were associated with a reduction in the duration of
mechanical ventilation and hospital stay [48].
6
International Journal of Cardiology Congenital Heart Disease 12 (2023) 100449
5. Microbiome
Nutrition cannot be completely understood without including the
gut microbiome in the equation. Intestinal flora interaction with nutri­
ments is crucial to understand the benefits or harms of a given diet. As an
example, trimethylamine (TMA) is produced by certain types of bacte­
rial phyla via conversion of L-carnitine or choline found in red meat.
TMA is transformed into trimethylamine-N-oxide (TMAO) in the liver,
which has been associated with the development of coronary artery
disease and poorer long-term clinical outcomes in chronic HF [49]. On
the other hand, a diet with a high fibre content enhances
butyrate-producing microorganisms, which have been shown to stabilise
the atherosclerotic plaque [50].
The interest in the gut microbiome and its contribution to different
pathologies has been increasing over the last few years. Evidence sug­
gests that the intestinal microbiome has an impact on different disorders
such as autoimmune, inflammatory bowel disease, obesity, and even
psychological conditions. In turn, certain diseases or situations (i.e.,
cardiopulmonary bypass) can alter the balance of the normal gut
microflora and produce intestinal dysbiosis. Different bacterial phyla
compose the microbiome: Bacteroidetes, Firmicutes, Actinobacteria,
Proteobacteria, Fusobacteria, and Verrucomicrobia. Bacteroidetes and
Firmicutes are the most predominant and are considered protective,
whereas Proteobacteria is a pro-inflammatory pathogenic bacteria
group. Therefore, the balance between the different bacterial phyla is
paramount. Gut-derived metabolites (TMAO, butyrate, nitric oxide, and
short-chain fatty acids), reflect alterations of the gut microbial flora and
have recently been shown to exert toxic effects on the heart, contrib­
uting to HF severity and adverse outcomes [51].
A case-control study revealed that perturbations of maternal gut
microbiota and plasma metabolites may be associated with a CHD risk in
the offspring. CHD baseline haemodynamic characteristics may play a
role in the disruption of the microbiome. A recent cross-sectional study
proved that children with unrepaired TOF have intestinal dysbacteriosis,
showing a clear interplay between the host characteristics and the
altered gut microbiome. As expected, cardiopulmonary bypass further
exacerbated these dysregulations.
Recently, Dan Feng et al. [52], elaborated about the interplay be­
tween CHD haemodynamics and the gut microbiome. CHD may induce
gut epithelial barrier dysfunction due to multiple stressors, such as
reduced cardiac output, hypoxemia, and increased intestinal venous
congestion. This generates a pro-inflammatory state that increases in­
testinal permeability, leading to bacterial translocation and an increase
in circulating toxins. In that way, proinflammatory bacterial perpetuate
the pro-inflammatory status, inducing reactive oxygen species and
cytokine activation. This reduces circulating nitric oxide (NO), which
affects NO-dependent vascular function, leading to maladaptive vaso­
constriction and subsequent development of pulmonary hypertension. It
is appealing to hypothesise that certain types of CHD, particularly those
more exposed to hypoxemia, low cardiac output states, and increased
central venous pressures, such as patients with Fontan circulation, may
be more prone to dysbacteriosis and its pernicious consequences (Fig. 4).
However, evidence of dysbiosis and its effects on CHD is still scarce.
Furthermore, the role of probiotics in the armamentarium of CHD
treatment is also unknown.
6. Conclusion
Patients with CHD are prone to nutrition disorders, including ab­
normalities in body composition such as overweight or obesity which,
along with other classical cardiovascular risk factors, places our
increasing and aging ACHD population at a higher risk of acquired CVD.
Thus, it is expected that dietary interventions proven to lower the car­
diovascular risk profile and risk factors, would be particularly beneficial
in this population.
These patients are also at risk of cachexia or sarcopenia, as well as
M. Lorente et al.
Fig. 4. The interplay between congenital heart diseases and microbiome: CHD may induce gut epithelial barrier dysfunction due to multiple stressors, inducing a pro-
inflammatory state that increases intestinal permeability, leading to bacterial translocation, and reducing reactive oxygen species and cytokine activation, reducing
circulating nitric oxide (NO), leading to maladaptive vasoconstriction and subsequent development of pulmonary hypertension.*CHD: congenital heart disease; HF:
heart failure; TMAO: trimethylamine-N-oxide; SCFA: Short-chain fatty acids.
macronutrient and micronutrient deficiencies, mainly derived from the
development of heart failure as a complication of their underlying car­
diac disease. Therefore, nutritional status evaluation becomes crucial in
a holistic approach for our patients and should be included in the
standard of care of all CHD patients.
While some dietary interventions or supplementations have shown
beneficial effects in specific CHD cohorts (i.e., iron reposition in cyanotic
patients), there are still enormous gaps in our knowledge. Given the
unique characteristics of some CHD (i.e., Fontan patients), dedicated
research should be undertaken to better understand the impact of di­
etary patterns, nutrient deficiencies, or the role of the microbiota, and
evaluate the benefits of specific interventions.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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