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Common long-term complications of adult congenital heart
disease: avoid falling in a H.E.A.P.
Ministeri M, Alonso-Gonzalez R, Swan L, Dimopoulos K
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal
Brompton Hospital, London, UK
NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National
Heart and Lung Institute, Imperial College London, UK
National Heart and Lung Institute, Imperial College School of Medicine, London, UK
Correspondence to:
Dr Konstantinos Dimopoulos MD MSc PhD FESC
Adult Congenital Heart Centre
Royal Brompton and Harefield NHS Foundation Trust
Sydney Street, SW3 6NP London, UK
Tel+44 2073528121 ext 2771, Fax+44 207351 8629
E-mail: [email protected]
1
Financial disclosure/Acknowledgements:
Dr Dimopoulos and Dr Alonso have acted as consultants and received unrestricted
education grants from Actelion, GSK and Pfizer. Dr Swan has received unrestricted
educational grants from Pfizer and Actelion. Dr Ministeri has received educational
grant support from the University of Catania, Italy.
2
Common long-term complications of adult congenital heart
disease: avoid falling in a H.E.A.P.
3
Summary
Advances in cardiology and cardiac surgery have transformed the outlook for patients
with congenital heart disease (CHD) so that currently 85% of neonates with CHD
survive into adult life. Although early surgery has transformed the outcome of these
patients, it has not been curative. Heart failure, endocarditis, arrhythmias and
pulmonary hypertension (HEAP) are the most common long term complications of
adults with CHD. Adults with CHD benefit from tertiary expert care and early
recognition of long-term complications and timely management are essential.
However, it is as important that primary care physicians and general adult
cardiologists are able to recognise the signs and symptoms of such complications,
raise the alarm, referring patients early to specialist adult congenital heart disease
(ACHD) care, and provide initial care.
In this paper, we provide an overview of the most commonly encountered long-term
complications in ACHD and describe current state of the art management as provided
in tertiary specialist centres.
Word count 7600 (including commentary)
Keywords: congenital heart disease, adult congenital heart disease, heart failure,
endocarditis, arrhythmia, pulmonary hypertension, complications
4
Introduction
The population of ACHD is rapidly expanding and ageing, with many patients well
into adult life and some in the geriatric age range.1 Despite significant advances in the
surgical management of patients with congenital heart disease, most surgery is still
reparative rather than corrective. In several situations, only partial repair is achievable
or the defect may not be repairable at all, and a definitive palliation or no intervention
may be offered. Many patients, even after “total repair”, face the prospect of further
operations and may often run into complications long-term. Such complications may
be difficult to manage and contribute to the significant morbidity and risk of
premature death described in this population. In fact, while ACHD patients with
isolated simple defects have a normal life-expectancy, the mortality in certain types of
ACHD (like Eisenmenger syndrome, complex congenital heart disease and Fontan
physiology) may be twice to seven times higher than in the general population .2
The clinical spectrum of ACHD is obviously wide, and the risk of complications
greatly depends on the underlying anomaly, previous repair and presence of residual
lesions. In some patients, events that would otherwise be deemed physiological, such
as pregnancy and delivery, may exacerbate symptoms and lead to significant
complications. Non-cardiac intercurrent diseases, such as chest infections, traumas or
conditions requiring non-cardiac surgery may also place an excessive load on patients
with reduced cardiac reserve. Finally, there is an established predisposition of many
ACHD patients to heart failure, endocarditis and arrhythmias, which should be
monitored for and treated promptly. Unfortunately, there is little information from
clinical trials to guide therapy in this growing population and management depends on
good understanding of the underlying anatomy and pathophysiology and
5
comprehensive experience of the multi-disciplinary team. Although data from patients
with acquired heart disease is informative, care must be taken to examine the
appropriateness of extrapolating these to patients with congenital cardiac lesions. The
objective of this review is to outline the emerging evidence and experience in the
management of four of the most common complications in ACHD: Heart failure,
Endocarditis, Arrhythmias, and Pulmonary Hypertension (HEAP).
6
Heart failure
Heart failure (HF) is a major cause of morbidity and mortality in ACHD patients. It is
defined as a combination of symptoms (e.g. dyspnea, peripheral edema) and signs
(e.g., pulmonary rales, increased central venous pressure) caused by an inability of the
heart to deliver a sufficient cardiac output to the organs and tissues.3 The term heart
failure in ACHD includes a huge variety of patients from those with native disease
(unrepaired or palliated), to those previously “repaired”. The reported incidence and
prevalence of heart failure in ACHD patients depends on the definition used: an
isolated rise natriuretic peptides has been described in up to 53%, while a combination
of decreased exercise capacity and elevated natriuretic peptide concentration is
present in 26% of this population.4,5 The hospitalization rate for symptomatic HF in
ACHD has been described as 1.2 per 1000 patient-years.6
Diagnosing HF in ACHD patients may be challenging. By definition reduced exercise
tolerance may be present from very early life in ACHD patients many of whom have
no experience of normal effort capacity. Furthermore, ACHD patients may be unable
to detect subtle changes in their limited exercise capacity; indeed, some ACHD
patients do not report significant symptoms, even those with complex congenital heart
diseases and documented effort limitation. 82.4% of patients with with “singleventricle physiology or with systemic right ventricles describe themselves as being in
NYHA class I or II.7
Heart failure is a continuum, from asymptomatic cardiac dysfunction with modest
neurohormonal activation, to severe symptomatic cardiac dysfunction with marked
neurohormonal activation.8 Patients reporting symptoms of HF tend to have more
advanced disease, with a significantly lower peak oxygen consumption on
7
cardiopulmonary exercise testing and more impaired systemic ventricular ejection
fraction compared to asymptomatic patients, as well as higher mortality. Evidence of
overt clinical heart failure has been reported in 40% of patients with Fontan
circulation, 32% of patients with congenitally corrected transposition of the great
arteries (ccTGA) and in 22% of patients with patients with transposition of the great
arteries (TGA) after atrial switch procedure (Mustard/Senning).7 In patients with
repaired Tetralogy of Fallot (TOF) the cumulative incidence of heart failure at 35
years of follow-up is low (3%), despite many patients needing reoperation or
developing arrhythmias.9 Patients with repaired atrio-ventricular septal defect
(AVSD) show a similar trend: many require surgical reintervention for left
atrioventricular valve regurgitation or other residual lesions, but the majority of
patients remain in a good functional class.10 Finally patients with simple TGA after
arterial switch operation present in the long term an excellent functional outcome,
even though our experience is limited to 2-3 decades.11 As surgery for CHD only truly
took off in the 1960s, there are limited data on the very long-term outcome of repaired
patients. An increasing number of adult CHD patients present after the 5th decade of
life with heart failure, especially those repaired in the earlier surgical era and/or late in
their life.1
The pathophysiology of HF in ACHD is multifactorial and may differ from noncongenital population. Several mechanisms contribute to HF including hemodynamic
factors,
such
us
chronic
pressure
and/or
volume
ventricular
loading;
electrophysiological factors such as persistent arrhythmias or long-term pacing;
myocardial dysfunction due to inadequate myocardial preservation during prior
surgery, longstanding cyanosis, myocardial fibrosis or diastolic dysfunction;
pulmonary vascular disease; etc. Systolic dysfunction of the systemic ventricle is the
8
rule in patients with a systemic right ventricle (Figure 1). Patients with a previous
Fontan operation, on the other hand, may have preserved systolic function of the
systemic ventricle, however, small changes in pulmonary vascular resistance will lead
to failure of the Fontan circulation which might be extremely difficult to manage.
Good understanding of the underlying anatomy, physiology and mechanisms
responsible for the development of the HF are essential to ensure improving outcomes
for these patients.
As the ACHD population ages, acquired heart disease may also contribute to the
development of heart failure.1 Systemic hypertension, coronary atherosclerosis,
myocarditis, alcohol and diabetes mellitus can adversely impact cardiac function. The
number of patients with a combination of congenital and acquired heart disease is
likely to rise as the ACHD population ages. Therefore, acquired morbidities, such as
coronary artery disease, seem to be key determinants of outcome in the older ACHD
population, in conjunction with the underlying congenital heart disease.12
Several markers have the potential of identifying ACHD patients at risk of developing
heart failure, assessing disease severity and evaluating the progression of heart failure
or treatment response: systolic ventricular function, diastolic ventricular function,
natriuretic peptides, exercise capacity, renal dysfunction and anaemia will be key in
risk stratifying these patients. Cardiopulmonary exercise testing is the best method for
assessing and quantifying exercise intolerance.13–15 Interestingly, exercise capacity in
ACHD patients is not directly related to resting systemic systolic ventricular function,
suggesting that exercise intolerance in this cohort is indeed often multifactorial.16
Furthermore, as shown by Diller et al., cardiopulmonary exercise testing is useful in
predicting morbidity and mortality.13 Peak VO2 is an independent predictor of
outcome in ACHD and patients with a peak VO2< 15.5 ml/kg/min are at threefold
9
increased risk of death and hospitalization. The VE/VCO2 slope and chronotropic
response to exercise are also a strong prognostic markers of death in ACHD
patients.15,17
Identification of the mechanism responsible for the development of heart failure in
patients with often complex anatomy and physiology is essential for their
management. Echocardiography provides a wealth of information, on cardiac
anatomy, haemodynamic lesions, systolic and diastolic properties of the ventricles and
the pericardium. Cardiovascular magnetic resonance imaging (CMR) is being
heralded as the modality of choice for the evaluation of heart function in ACHD
patients.18 The right ventricle (RV) is commonly impaired in both repaired and
unrepaired patients and CMR allows accurate assessment of RV volumes and
hemodynamic lesions.
Management guidelines for the treatment of HF in ACHD are lacking, largely due to
the fact that ACHD patients are commonly excluded from HF clinical trials, and there
is a paucity of data to guide therapies in this growing population. The goal of HF
therapy in ACHD is similar to that in patients without ACHD: reversal of pathologic
remodelling,
restoration
of
adequate
systemic/pulmonary
output,
and
improvement/resolution of symptoms.19,20 Arrhythmias should be treated promptly
and pacemaker settings optimised. Pulmonary hypertension should be identified and
treated appropriately (see below). Other reversible causes of HF and precipitating
factors such as ischemic heart disease, anaemia, systemic hypertension, parenchymal
pulmonary disease, sleep apnoea and obesity should be sought and, when possible
treated.21–23
10
Surgical or interventional therapy
Cardiac hemodynamic lesions, if present, should be the first target in the effort to
improve the clinical status of ACHD patients presenting with HF. Potential
therapeutic options include surgical or interventional relief of obstructive lesion,
repair of valve abnormalities and elimination or reduction of the shunts. The vast
majority of procedures performed on ACHD patients are reoperations. This implies an
increased perioperative risk related to redo sternotomy, long bypass times and
technical challenges such as calcified conduits and should be performed by
experience surgeons in a specialised ACHD centre. This is particularly true for
complex high-risk operations such as conversion of a failing atriopulmonary Fontan
circulation to a total cavopulmonary connection (TCPC conversion). Patients with the
"older version" of the Fontan circulation (atrio-pulmonary connection) over time
develop severe right atrial dilation, arrhythmias, intracavitary thrombi and
arrhythmia.24,25 Conversion to the more modern TCPC is a procedure that should only
be performed by surgeons experienced in this operation and excludes the right atrium
as well as providing more optimal haemodynamics.26 Patients with systemic right
ventricle often develop severe tricuspid regurgitation, which results in ventricular
overload and affects prognosis. Although tricuspid valve replacement might be
indicated in this population, this should be decided and performed in a specialised
ACHD centre.27
Medical therapy
Diuretics are the mainstay of HF treatment in symptomatic patients, with attention on
maintaining adequate preload in patients with severely impaired right ventricles and
those with Fontan circulation who depend on some rise in central venous pressures to
11
maintain pulmonary blood flow. Decompensated heart failure in patients with a
“restrictive” ventricular physiology (i.e. severe diastolic dysfunction as encountered
for example in elderly patients with late repair of tetralogy of Fallot) or pulmonary
hypertension and concomitant renal dysfunction is particularly challenging to manage
and may require prolonged hospital admissions for intravenous diuretic, with the
possible addition of inotropes (e.g. dobutamine in pulmonary hypertension
patients).28–31 Patients with decompensated RV failure develop significant secondary
hyperaldosteronism and, therefore, spironolactone should be added to loop-diuretics
in order to achieve optimal diuresis.32,33
Neurohormonal activation is common in ACHD and, despite the lack of strong
evidence, many ACHD centres commonly use angiotensin-converting-enzyme
inhibitor (ACE inhibitors), angiotensin receptor blockers and aldosterone antagonists
in ACHD patients with heart failure.33 However, few randomized trials have been
performed in this population, mostly using surrogate endpoints to evaluate the effects
of drug treatment. Van der Bom et al. investigated the impact of renin-angiotensin
inhibition using valsartan on systemic RV function in a randomized clinical trial that
included 88 patients with systemic right ventricles.34 In their study, there was no
significant treatment effect of valsartan on right ventricular ejection fraction after 3
years follow-up. However, in the subgroup analysis of the symptomatic patients, there
was an improvement in RV ejection fraction of 4.5% compare to the placebo group.
Furthermore, there was an improvement in RV volumes in asymptomatic patients. In
the setting of repaired TOF with RV or LV dysfunction, Babu-Narayan et al.
investigated in a double-blinded placebo-control trial, the impact of ramipril on RV
systolic function in patients with repair TOF and moderate-severe pulmonary
regurgitation.35 The study showed no difference in the primary endpoint, CMR
12
derived RV ejection fraction (EF), as well as in long-axis function assess by
echocardiography. Various small observational studies have investigated the effects of
beta-blockers in different ACHD populations. Bisoprolol did not improve RV-EF in
33 patients with TOF, but resulted in an increase in natriuretic peptides level in the
bisoprolol arm.36 Small uncontrolled studies suggested some beneficial effects of betablockade in patients with a systemic RV.37,38 The aldosterone receptor blocker
epleronone resulted in a favourable change in collagen turnover biomarker profiles in
patients with a systemic RV, suggesting that myocardial fibrosis might be a
therapeutic target in this setting.39 Pulmonary arterial hypertension (PAH) targeted
therapies are able to improve the functional status on patients with Eisenmenger
syndrome (a detailed discussion of these therapies is provided in the relevant chapter).
Overall the design and power of these ACHD heart failure studies makes it difficult to
conclude if these therapeutic agents are of value or not.
Cardiac resynchronization therapy (CRT)
CRT represents another therapeutic option in ACHD patients with HF, underlying left
(systemic) ventricular dysfunction and evidence of intraventricular conduction delay.
Despite mounting evidence of ventricular dyssynchrony in patients with CHD,
randomized trials of resynchronization in this population are lacking. The vast
heterogeneity in anatomy and physiology makes identification of ideal candidates for
CRT difficult. Moreover, it is still unclear whether patients with systemic right
ventricles, univentricular circulation or isolated subpulmonary (right-sided)
ventricular dysfunction can benefit from CRT, beyond the obvious technical
difficulties in implanting such as device.
13
Three retrospective studies of CRT in heterogeneous CHD populations have been
published.40–42 Epicardial device placement was common (up to 50%). Clinical
response was not uniformly defined and included improvement in EF or functional
class. Using these endpoints, 32–87% of patients demonstrated improvement with
CRT. However, there are still insufficient data to determine which anatomic
subgroups derive the greatest benefit from CRT. According to the recently published
consensus guidelines for arrhythmia management in the adult with CHD, patients with
systemic LV failure and electromechanical dyssynchrony should have similar
indications to non-ACHD adult CRT patients.43 Congenital or post-operative
atrioventricular block with chronic RV pacing accounts for 65% of CRT
implantations in ACHD subjects.
Patients with systemic RV failure are those with complete TGA after atrial switch
procedure, or those with congenitally corrected transposition (ccTGA). One study
specifically addressed potential indications for CRT in this population.44 If the
selection of candidates for CRT was based solely on NYHA class II or more
symptoms in the presence of a QRS duration >120 ms, 9.3% of patients with atrial
switch procedure would qualify, compared to 6.1% of those with ccTGA. In small
case series of patients with systemic right ventricles, CRT has been shown to increase
RV ejection fraction, decrease QRS duration, increase peak VO2, and improve
functional class.42,43 However, tricuspid valve regurgitation does not appear to be
significantly influenced by CRT and it is unlikely that patients with severe tricuspid
regurgitation and ventricular dysfunction will benefit from CRT.
The majority of patients with repaired TOF typically have a right bundle branch block
(RBBB) and resultant dysynchronous contraction of the RV. However, non-ACHD
patients with RBBB have demonstrated disappointing results with CRT compared to
14
those with left bundle branch block.47 It is still unclear whether RV pacing improves
RV performance in repaired TOF patients, as the QRS prolongation may be a
consequence of RVOT pathology rather than the body (inlet) of the RV. There are no
long- term outcome data on CRT response in adults with repaired TOF, although
short-term results have shown some improvement in heart failure symptoms.48
Heart transplantation
Ultimately heart transplantation or heart-lung transplantation should always be
considered in ACHD patients with refractory HF. In countries like Canada, transplant
numbers have increased over the past two decades and the congenital lesions most
commonly requiring heart transplantation are failing Fontan, Mustard/Senning
procedures and congenitally corrected transposition of the great arteries.49 These
patients are typically younger than other adults listed and have a lower body mass
index as well as fewer comorbidities.50 Standard risk stratifiers used for listing
patients for transplantation may not be applicable to ACHD. While reduced exercise
performance has been associated with poor survival in ACHD overall and may
prompt transplant listing, this has not been consistent across all diagnoses and cannot
be depended upon. Specific risk factors to be considered are sensitization from
previous transfusions, pregnancies or homograft implantations. Antibodies can persist
for more than a decade after heart surgery. Elevated pulmonary vascular resistance,
distorted pulmonary artery anatomy, arteriovenous fistulae and pulmonary venous
hypertension require careful haemodynamic evaluation by a congenital cardiologist.
Other surgical risks derive from anatomical abnormalities including abnormal
position of organs or vessels (eg, situs inversus, malposition of the great arteries or
venous anomalies) as well as previous cardiac operations that may add significant
15
technical problems. Once listed, CHD patients are more likely to be listed at lower
urgency (64% of CHD patients are listed as status 2 compared to 44% of non-CHD
patients), despite a higher rate of complications once on the transplant list.50 This
discrepancy may, in part, be explained by lower utilisation of mechanical circulatory
support among CHD patients. Early post-transplant mortality is increased in patients
with CHD as are post-transplant complications, including need for dialysis and
prolonged intensive care unit stay. The most frequent causes of early post-transplant
mortality in patients with CHD are haemorrhage and acute graft failure. Nonetheless,
10-year survival is better in CHD than in non-CHD populations. Risk factors for
adverse transplant outcomes in ACHD patients include prior Fontan operation,
complex anatomy, re-do sternotomy and pulmonary hypertension.
Recently, given the increasing complexity of the ACHD population, and in light of
advancements in the field, multi-organ transplantation may also be a consideration. In
the Mayo Clinic experience of 45 patients undergoing transplant procedures (age
range, 1 month to 65 years), three patients underwent successful combined-organ
transplant
(two
heart/liver
and
one
heart/kidney).51
Combined
heart-liver
transplantation may be appropriate for many patients with failing Fontan circulation,
in whom a chronic raised in central venous pressure can cause significant liver
derangement, cirrhosis and even hepatocellular carcinoma.
More effort should be made in developing adequate criteria for referring ACHD
patients to transplant. Current criteria for listing non-ACHD patients do not apply to
the majority of the ACHD population, especially those with complex cardiac anatomy
and physiology. Multi-organ failure is not uncommon in patients with Fontan
circulation, prohibiting heart transplantation or requiring combined heart-liver
transplantation, which increases perioperative risks. Perhaps, in ACHD, the indication
16
for referring to heart transplant should not be based primarily on functional class or
exercise intolerance, but on evidence of organ failure, such as renal or liver
dysfunction. The timely selection of optimal candidates remains challenging and large
congenital centres need to work together to optimise transplantation outcomes in
ACHD.
Ventricular assist devices
HF patients with CHD are more likely to have right-sided HF, pulmonary
hypertension or residual shunts, which may make them less attractive candidates for
ventricular assist devices (VADs).52,53 The use of VADs in ACHD patients is limited
to case reports or small case series and VADs are rarely used in this population. A
group of ACHD patients that is likely to benefit the most from this approach are
patients with a systemic RV. The new devices are smaller overcoming the problem of
inserting them in a heavily trabeculated ventricle. Peng et al., recently reported a
small series of 7 patients with systemic RV failure who received the HeartWare
(HeartWare International Inc, Framing- ham, MA) VAD.54 The indications was
bridging to transplantation, with the aim to support the systemic RV and/or reduce
pulmonary pressures. The authors showed that this third generation VAD provides
durable support for the RV in both situations. With the current advances in
technology, with smaller and more efficient VADs in the market, the use of VADs in
the ACHD population will likely increase exponentially. In patients with single
ventricle physiology and a Fontan circulation, the use of VADs is more challenging
because of the need to achieve and maintain a balance between different variables,
including cardiac output, ventricular load, pulmonary artery pressure and Fontan
filling pressures. Despite the fact that a left-VAD could help unload the ventricle and
17
reduce post-capillary pressures in the pulmonary circulation, the increase in cardiac
output may lead to an increment in pressures in the Fontan pressures, causing hepatic
and venous congestion. More data are required to understand the role of VADs in this
setting.55,56
18
Endocarditis
The reported incidence of infective endocarditis (IE) in CHD is two times higher than
in the general population.57 Virtually any congenital defect may predispose to the
development of IE and the risk of this actually occurring is not negligible. Moreover,
the risk of IE in the ACHD population is not only related to the underlying congenital
defect, but also the previous surgical and percutaneous interventions, resulting in a
cumulative risk for infection (Figure 2). In our experience in the ACHD population,
the most common site for IE is the left ventricular outflow tract, regardless of whether
previous surgery had been performed.58 Unoperated restrictive VSDs were the second
most common lesion, followed by cyanotic CHD (25% of the total CHD patients with
IE); TOF was the most common cyanotic condition in patients presenting with IE.
Other lesions included pulmonary atresia with ventricular septal defect (VSD), single
ventricular physiology, transposition of the great arteries, atrioventricular septal
defect (ASD) with pulmonary stenosis, truncus arteriosus and VSD with Eisenmenger
physiology. Dental or surgical procedures (especially when followed by a long stay in
the intensive care unit), intravenous therapy (especially via a central intravenous
catheter), cardiac diagnostic and interventional procedures, body piercing, acne and
tattooing, and the insertion and delivery of intra-uterine devices are considered
possible portals of entry for infections, even though strong evidence is lacking.
Causative organisms are most often staphylococcal or streptococcal species, but
unusual bacteria or fungi may be involved. Transcatheter (percutaneous) pulmonary
valve implantation is a relatively novel therapeutic option and is currently the
treatment of choice for patients with right ventricular outflow tract conduit
dysfunction. Short and medium term outcomes of patients undergoing percutaneous
19
pulmonary valve implantation appear to be good. However, some concerns have been
raised with regards to the IE risk of these valves, with a reported annualized rate of
0.88%-2.4% per patient-year, possibly higher compared to homograft pulmonary
valve impants.59,60
The clinical manifestations of infective endocarditis are highly variable and a high
level of suspicion is required to ensure timely diagnosis and treatment. The extent of
local involvement of the myocardium or valves, embolization of vegetations and the
activation of immunological mechanisms all play a role in defining clinical
presentation. Despite the potentially devastating cardiac and systemic effects of IE,
mortality related to IE has decreased substantially in ACHD to approximately 10%,
much lower than in the non-congenital population. This is thanks to improvements in
the diagnosis of IE, antimicrobial treatment and cardiac surgery, but also due to the
fact that it affects younger people, and is often right-sided, hence, embolic or other
complications have less devastating effects (e.g. destruction of the pulmonary
valve).61,62 Moreover, ACHD patients with IE are most likely to be treated in tertiary
ACHD centres and benefit from high levels of multidisciplinary IE expertise. IE
should be suspected in all ACHD patients presenting with fever, night sweats or
newly manifesting heart failure. Delayed diagnosis and referral, up to 1 month or well
beyond, and inappropriate initial antibiotic therapy are common and can adversely
affect the outcome. A substantial proportion (25-60%) of patients with bacterial
endocarditis require elective or emergency surgery during or soon after the episode of
IE in order to replace intracardiac or intravascular infected material, repair native
lesions or as a result of failure of medical therapy to control the infection.61
As the diagnosis of endocarditis is often difficult, attempts have been made to
establish criteria that allow for a firm (or firmer) diagnosis. Modified Duke criteria are
20
recommended by the recent ESC Guidelines for the management of infective
endocarditis, with the addition of newer imaging modalities (cardiac/whole-body CT
scan, cerebral MRI, 18F-FDG PET/CT and radiolabelled leucocyte SPECT/CT),
which may improve the sensitivity of these criteria, especially in difficult cases (see
Table 1).63 Any imaging modality used in ACHD, especially in the setting of IE,
requires very high level of expertise, in view of the complex anatomy and presence of
artificial material, which can reduce the rate of detection of vegetations or other
features of IE. It is recommended that all ACHD patients presenting with IE should be
evaluated and managed at an early stage in an ACHD reference centre by a
multidisciplinary "Endocarditis Team", including ACHD cardiologists, surgeons and
anaesthetists, microbiologists and experts in ACHD imaging. Moreover, access to
neurology and neurosurgical facilities is important.
Medical therapy
The purpose of IE treatment is to sterilize infected cardiac tissue and, by so doing, to
limit the extent of damage and prevent life-threatening complications such as
systemic embolism and cardiac failure. In most instances, adequate antibiotic
treatment is all that is required, but in selected cases, surgery becomes necessary,
sometimes early in the course of the disease. Unless the condition of the patient is
deteriorating, initiation of therapy can at times be delayed until the organism has been
identified and antibiotic sensitivities determined or at least until numerous blood
cultures are obtained. In all instances, antibiotic treatment should never be started
until an adequate number of blood cultures (at least 4) from different sites have been
taken. The consensus is that bactericidal drugs should be used in preference to
bacteriostatic agents and bolus intravenous injections are preferable and possibly
more effective than intravenous infusions or intramuscular administration. Drug
21
treatment of prosthetic valve endocarditis (PVE) should last longer (at least 6 weeks)
than that of native valve endocarditis (2–6 weeks). PVE is the most severe form of IE
and occurs in 1–6% of patients with valve prostheses.
Surgical therapy
Surgery may become necessary during the active phase of the disease, but is
associated with significant risks. However early surgery is justified when (1) medical
treatment is failing, particularly when there is hemodynamic deterioration; (2) large
mobile vegetation are noted on echocardiography (especially in left-sided IE); (3) a
mechanical valve prosthesis is infected (by staphylococci or non-HACEK gramnegative bacteria); (4) there is evidence of an infective abscess; and (5) when fungal
endocarditis is encountered.63
Prevention and antibiotic prophylaxis
Given the prognosis, morbidity and high cost of management of IE, prevention and
early detection are paramount. All ACHD patients must be educated on their
condition and related complications, including IE.64
This should be part of the
transition program from paediatric to ACHD services and should be repeated on every
consultation thereafter. When the patients are aware of the risk of IE and the possible
signs and symptoms, primary prevention and early diagnosis become easier. IE
prevention includes a good oral and skin hygiene. The mouth, and in particular
invasive dental procedures that cause disruption of the mucosa, are felt to be a major
portal of entry of organisms to the bloodstream. However, cosmetic tattooing and
piercing, are also discouraged in this group. Indication for antibiotic prophylaxis are
reported in the recent ESC Guidelines for the management of infective endocarditis
and are limited in patients with cyanotic heart disease, those with previous IE,
22
prosthetic valve, or prosthetic material/devices with an adjacent residual shunt or
within 6 months of implantation.63
23
Arrhythmias
ACHD patients are prone to arrhythmias given the natural history of their underlying
congenital heart disease (CHD), the long-standing nature of their hemodynamic
alterations, and the consequences of surgical interventions. A recent study showed
that, from the period 1998 to 2006, there was a 112 % increase in the number of
ACHD patients that were admitted for emergency care in the United States with a
diagnosis of arrhythmia.65 Bouchardy et al. reported that atrial arrhythmias occurred
in 15% of adults with congenital heart disease.66 The lifetime incidence increased
steadily with age and was associated with a doubling of the risk of adverse events.
The presence of complex CHD, significant residual haemodynamic lesions or
ventricular dysfunction, significantly increases the risk of arrhythmias, which should
be treated in a timely fashion.
Bradyarrhythmias
The most common bradyarrhythmias seen in ACHD are sinus node dysfunction
(SND) and complete heart block (CHB). SND occurs predominantly in patients who
have had surgery near the sinoatrial (SA) node (Mustard and Senning operations and
the various iterations of the Fontan operation). It more often appears insidiously after
long-term follow-up, not only in the immediate post-operative phase. Patients with
left atrial isomerism, by definition, lack a normal sinus and typically present with a
low (or other) atrial or junctional rhythm. The loss of sinus rhythm could be
dangerous for Fontan patients as well as patients with severely restrictive ventricles:
the loss of atrial contribution significantly affects cardiac output.67 CHB is less
common in the overall adult congenital population and is most commonly seen in the
24
immediate postoperative period. However, CHB can occur spontaneously in patient
with atrioventricular septal defects or ccTGA.
Pacemaker implantation can be a significant endeavour in complex ACHD
patients.68,69 Thorough understanding of cardiac and vessel anatomy, with particular
attention to prior operative notes is essential. At times, the lack of patent peripheral
veins or intracardiac anatomy itself may prohibit access to cardiac chambers, thus,
requiring epicardial pacing (e.g. in Fontan patients). It is important to bear in mind
that patients with transvenous pacing or defibrillators and intracardiac shunts are at
risk of paradoxic emboli and, thus, anticoagulation should be considered.
Supraventricular tachycardia
Supraventricular tachycardia (SVT) is an important cause of morbidity for many
patients with CHD. SVT mainly occurs after cardiac surgery and is often incisional
atrial reentrant tachycardia (IART) related to a previous atriotomy scar. Its incidence
is highest in patients who have undergone Mustard or Senning repair for d-TGA or
Fontan procedure. In particular, >50% of older patients with an atriopulmonary
Fontan operation develop SVTs within 10 years of repair, compared to <10% for
those with the newer total cavopulmonary connection (Figure 3).70,71 Typical atrial
flutter can occur in almost all forms of CHD but is most often seen in the setting of
unoperated atrial septal defect (ASD) or other conditions associated with a dilated
right atrium. Up to 10–25 % of patients with Ebstein’s anomaly can develop
atrioventricular reentrant tachycardia (AVRT) secondary to an accessory pathway
(Wolff-Parkinson-White Syndrome).
SVTs is typically poorly tolerated in complex ACHD patients and acute management
can be a challenge due to hemodynamic instability. As a general principle, it is
25
important to convert patients to sinus rhythm in the most expeditious manner and a
rate control strategy should be, at best, only temporary and only used in very stable
patients. Synchronized electrical cardioversion is the most commonly used means for
conversion to sinus rhythm in ACHD centres, under the care of experienced
anaesthetists. Pharmacological therapies are less commonly used: amiodarone is
probably the most used antiarrhythmic in ACHD, followed by sotalol, beta-blockers
and other antiarrhythmics. Adenosine can be used but is usually inefficient with the
most commonly encountered intra-atrial tachycardias.
Long-term oral anticoagulation is recommended in the complex ACHD patients and
SVT or atrial fibrillation, and should be considered in those with moderate forms of
ACHD.43 It is unlikely that the thromboembolic risk associated with simple non
valvular forms of CHD is sufficiently high to justify long-term anticoagulation as a de
facto approach, such that the decision to pursue antiplatelet or anticoagulation therapy
in this subgroup of patients may be guided by established non-ACHD risk scores for
stroke (e.g., CHA2DS2-VASc) and bleeding risk (e.g. HAS-BLED).72 Catheter
ablation has emerged as an excellent early therapeutic option in experienced ACHD
centres. With standard incorporation of 3-dimensional mapping technology for precise
localization of tachycardia circuits and the routine use of irrigated-tip radiofrequency
ablation catheters, acute success rates of approximately 80% can be achieved.73 Late
recurrence of the clinical IART or new reenty “circuits” after catheter ablation is
observed in approximately one-third of patients, with higher risk in patients who have
undergone the Fontan procedure.74 Ablation, when achievable and in the hands of
experienced operators, is felt to be superior to long-term antiarrhythmic treatment,
even if it only reduces the burden of SVT episodes. For patients with refractory IART,
or if surgery is planned for hemodynamic indications, surgical ablation with an atrial
26
MAZE procedure can be beneficial. Recurrent refractory SVT is an indication for
undertaking TCPC conversion of older Fontan circuits plus right atrial Maze.20,43
Ventricular arrhythmias
Sustained ventricular arrhythmia is presumed to be the most common mechanism for
sudden cardiac death in the ACHD population. Ventricular tachycardia (VT) is
typically encountered late after repair of TOF, but can also develop in a wide
spectrum of congenital lesions. It is felt to be related to prior ventriculotomy scars or
ventricular fibrosis.
Non-sustained ventricular tachycardia is not uncommon in
ACHD and is often completely asymptomatic, detected during ambulatory or device
monitoring.
For patients with documented sustained VT or cardiac arrest, definitive therapy
including ICD implantation and catheter ablation, have largely replaced
pharmacological management.75 All patients presenting with a VT or cardiac arrest
should be investigated for coronary artery disease, on-going heamodynamic lesions,
ventricular dysfunction, long-QT, RV arrhythmogenic cardiomyopathy or other
syndromes predisposing to malignant arrhythmias. Invasive hemodynamic and
electrophysiological evaluation may be required and there is a role, albeit limited, for
VT ablation.
Risk assessment for sudden cardiac death (SCD)
One of the most challenging clinical problems in ACHD is the selection of patients
who could benefit from primary prevention of sudden cardiac death (SCD). This
needs to be weighed against the risk of Implantable Cardioverter-Defibrillator (ICD)
related complications. The risk of SCD is time dependent and progressively increases
27
after the second decade of life. Thus far, no randomized clinical trials have been
performed to delineate risk factors for SCD or the benefit of primary prevention
therapies in ACHD. TOF is the most carefully studied lesion with regards to VT/SCD.
In adults with repaired TOF, SCD is the most common cause of late mortality, with an
incidence of 2% per decade.76 However, despite numerous cohort studies that have
identified factors associated with ventricular arrhythmias and sudden death, risk
stratification remains imperfect. A probabilistic approach using a combination of noninvasive risk factors and programmed ventricular stimulation, as suggested by Khairy
et al., may be a useful strategy to select patients at high risk who may benefit from an
ICD (Table 2).77 An ICD can be problematic in young patients: beyond the need for
multiple generator replacements and lead revisions, there is a significant risk of
inappropriate shocks. In fact, many of these patients are likely to develop SVTs,
which in great part account for the high rate of inappropriate shocks, especially in
TOF patients.78
28
The lack of evidence on the use of ICDs in complex CHD makes
clinical decision making even more difficult. Sudden death is not
uncommon in these patients and implantation of an ICD may be
reasonable, e.g. in adults with single ventricle physiology or a
systemic right ventricle and severely reduced systemic
ventricular function, especially when additional "risk factors"
are present, such as complex ventricular arrhythmias,
unexplained syncope, NYHA functional class III or a prolonged
QRS duration >140 ms40. In patients, in whom access to the
subpulmonary ventricle from the venous system is anatomically
impossible, implantation of epicardial and/or subcutaneous leads
is required. This is an invasive procedure, with higher lead
failure rates and the possibility of developing restrictive
“pericardial” physiology related to defibrillation patches.79
29
Pulmonary Hypertension
Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure
(PAPm) ≥25mmHg.80
PH can be distinguished in precapillary or post-capillary,
depending on whether pulmonary wedge (or left atrial) mean pressure is ≤ or
>15mmHg and whether pulmonary vascular resistance exceeds (or not) 3 Wood units
on right heart catheterization (RHC). It is important to distinguish between PAH-CHD
and other (post-capillary) forms of PH related to CHD, as only the former benefit
from targeted PAH therapies.
Post-capillary PH is common in ACHD and is related to valve or myocardial disease,
or pulmonary venous stenosis. Precapillary PH (pulmonary arterial hypertension,
PAH) due to congenital heart disease (PAH-CHD) is also quite common and affects
up to 3% of patients.81 Eisenmenger syndrome is the extreme end of the spectrum of
PAH-CHD, in which there is severe pulmonary vascular disease leading to reversal of
the shunt and cyanosis. A description of the various types of PAH-CHD is given on
Table 3.
While pulmonary vascular disease in CHD patients does not differ in terms of
pulmonary histology compared with idiopathic or other types of PAH, there are
important differences with regards to the pathophysiology and management. Cardiac
catheterisation is essential for the diagnosis in most cases, with calculation of
pulmonary vascular resistance (PVR), especially in patients with persistent L-R
shunting. An exception to this rule may be Eisenmenger syndrome, in cyanotic
patients with a post-tricuspid shunt (VSD or patent ductus arteriosus) in the absence
of pulmonary stenosis, in whom the diagnosis may be established with a high degree
of certainty by echocardiography in expert centres. In all other cases, accurate
30
estimation of PVR, with calculation of pulmonary blood flow using the direct Fick
method, is recommended.81
Surgical and interventional management
Surgical or transcatheter closure of the defect is contraindicated in all Eisenmenger
patients, and those with PAH in the presence of a small defect, as the defect is felt to
act as a relief valve for the right ventricle and boosts cardiac output through right-left
shunting, at the expense of chronic cyanosis.82 In a subgroup of patients with L-R
shunt, surgical or percutaneous repair may be indicated. Experts recommend closure
of defects only when there is no significant pulmonary vascular disease (PVRi <
4Wood units × m2). When PVRi exceeds 8Wood units×m2, no intervention should be
undertaken. Patients with ‘borderline’ PVRi (between 4 and 8Wood units × m 2) are
best assessed individually in ACHD centres.80,81
Although mortality rates in PAH-CHD are frequently reported as being more
favourable than those for patients with PAH of other etiology, most studies focus on
Eisenmenger syndrome and follow adult survivors (i.e. a prevalent rather than
incident population, see immortal time bias).83 PAH-CHD patients who have
undergone corrective surgery appear to have a significantly worse prognosis than
Eisenmenger patients, likely due to the lack of a "relief" valve.
Medical management
Ideally, all PAH-CHD should be followed up in tertiary centres with expertise in both
CHD and PAH, avoiding common pitfalls and inappropriate practices of the past,
such as routine venesections in Eisenmenger patients and absolute exercise restriction.
Their management is challenging and greatly based on clinical expertise rather than
31
solid evidence, which is lacking.81 Supportive therapy includes iron supplementation,
diuretics and oral anticoagulation aimed at reducing symptoms and treating or
preventing complications related to chronic hypoxia, haematological and coagulation
disorders, congestive cardiac failure, rhythm disturbances and infection.84 For
example, simple measures such as adequate hydration, especially at the time of
infections or fluid loss (diarrhoea or vomiting), are important for Eisenmenger
patients, in order to avoid hyperviscosity symptoms and renal dysfunction, whilst
taking care to avoid congestion. Prompt treatment of respiratory tract and other
infections, early cardioversion of patients presenting with arrhythmias and good
dental and skin hygiene are paramount. On the other hand, routine venesections
promote iron deficiency and seem to increase rather than decrease the risk of
cerebrovascular events.85,86 All non-essential surgery should be avoided when this
cannot be performed under local anaesthesia, as both general anaesthesia and sedation
carry significant risks in PAH-CHD. Finally, pregnancy is contraindicated in PAHCHD, as risks remain prohibitive despite modern treatment.87,88
The use of oral anticoagulants in Eisenmenger syndrome is controversial: a high
incidence of pulmonary artery thrombosis and stroke is reported, but there is also an
increased risk of bleeding, including potentially life-threatening haemoptysis (Figure
4).89 Given the lack of evidence, guidelines do not recommend the use of
anticoagulants in PAH-CHD, but suggest they may be considered in patients with
pulmonary artery thrombosis and signs of heart failure in the absence of previous
significant haemoptysis.80
Nifedipine and other calcium channel blockers are
contraindicated in Eisenmenger syndrome due to the risk of worsening hypoxemia
through a drop in systemic compared to pulmonary vascular resistance and the
subsequent increase in right-to-left shunting. Moreover, strenuous or extreme
32
isometric efforts should be discouraged in PAH-CHD patients, but mild-to-moderate
physical activity tailored to the patients’ exercise capacity and underlying
cardiorespiratory physiology is recommended in order to limit the detrimental effects
of physical deconditioning.90,91
Available advanced therapies (ATs) for PAH target vasoconstriction and proliferation
of smooth muscle cells in the pulmonary arterial bed. To date, three identified major
pathways controlling these processes have been translated into clinical practice: (a)
the prostacyclin-mediated pathway, (b) the nitric oxide-mediated pathway and (c) the
endothelin-mediated pathway. The widespread use of oral ATs in PAH-CHD began in
2006, after the publication of the BREATHE-5 the first randomized, double-blind,
placebo-controlled trial in patients with Eisenmenger syndrome.92 In this study,
bosentan (endothelin receptor antagonist) had a beneficial short-term effect on
exercise capacity and cardiopulmonary hemodynamics in WHO class III patients,
while demonstrating to detrimental effects on oxygen saturations. The beneficial
effects of bosentan on exercise capacity were sustained up to 1 year in the open-label
extension study.93 This study remains the only large Industry-led randomised
controlled study in the field of PAH published to date. Subsequently, smaller studies
on other drugs including Sildenafil and Tadalafil (phosphodiesterase inhibitors, acting
on the nitric oxide-mediated pathway) demonstrated a significant improvement in
exercise capacity and hemodynamic parameters in Eisenmenger patients.94,95 A
minority of patients with PAH-CHD after repair of the defect have been included
together with iPAH and connective tissue-related PAH in large randomized trials
using Treprostinil, Sildenafil, and Sitaxentan (now withdrawn from the market), as
well as the EARLY study demonstrating the beneficial effect of bosentan on PAH
patients in functional class II.96–99 The effect of ATs on exercise capacity and
33
functional class appears to be maintained over several years, despite some initial data
suggesting loss of efficacy after the first year.100,101
The prostacyclin analogue epoprostenol has been studied in the setting of PAH-CHD,
showing favourable effects on haemodynamics and exercise capacity in small nonrandomised cohorts.102 Concerns have been raised in relation to the risk of line
infections leading to endocarditis in patients with CHD, as well as the risk of
paradoxic emboli, but have not been substantiated in recent published cohorts.
Limited evidence does also exist on the use of inhaled iloprost and subcutaneous
treprostinil in PAH-CHD patients, which remain valid alternatives.
Evidence on the use of advanced therapies in combination, sequentially or upfront, is
lacking in PAH-CHD, as opposed to other types of PAH (e.g. iPAH) in which
sequential and upfront combination have been shown to decrease the risk of clinical
deterioration compared to monotherapy.103–105 Most PAH-CHD centres will, however,
nowadays treat patients who fail monotherapy with a combination of drugs.
Transplantation is the only “curative treatment” available for PAH-CHD, but is not
without limitations. Lung transplantation with repair of the underlying cardiac defect
or heart and lung transplantation can be performed at an acceptable risk in well
selected Eisenmenger patients, resulting in an improvement in symptoms and quality
of life. However, few centres can offer repair of a CHD defect at the time of
transplantation, hence, requiring heart-lung transplantation. Eisenmenger patients who
reach adulthood often remain clinically stable for many years or decades. By the time
transplantation is considered, they are often unsuitable candidates due to established
multiorgan failure (Figure 5).2,30 This, together with the chronic shortage of donors,
the increased risk of perioperative bleeding and suboptimal long-term survival after
34
heart-lung transplantation, highlight the importance of developing alternative
therapies aimed at improving the quality of life and survival of these patients.
35
Expert commentary
In this paper, we propose an acronym to remind non-ACHD specialists of the most
commonly encountered complications of ACHD. Heart failure, endocarditis,
arrhythmias and pulmonary hypertension (HEAP) are not uncommon in ACHD and
these patients are likely to present in local emergency and cardiac services rather than
specialist hospitals. All cardiologists and emergency physicians should be equipped to
acutely manage these and other complications, under the guidance of the nearest
ACHD centre, and be able to promptly transfer the patients to specialist care.
Established congenital networks, encompassing centres of different levels of expertise
under the guidance of a tertiary specialist ACHD team, provide the best possible care
for patients, whilst ensuring that local physicians are adequately supported.
Key issues:
The management of ACHD patients differs significantly to that of other (acquired)
cardiac conditions and requires significant expertise.
Specialist tertiary centres should work closely with local ACHD and general
Cardiology centres to provide good care for ACHD patients as close to home as
possible.
A multidisciplinary approach including electrophysiology, surgeon, clinical
cardiologist with experience in ACH could be the way for a good decision.
All cardiologists and general physicians should be aware of the most common longterm complications encountered by ACHD patients, who are likely to present to local
emergency departments.
36
H.E.A.P. i.e. heart failure, endocarditis, arrhythmias and pulmonary hypertension are
commonly encountered in ACHD and this paper provides an overview of the
management of these complications for the general physician and cardiologist, who
are likely to be the first to encounter these in the primary or secondary care setting.
37
Five year view:
An increasing number of adults with CHD will require expert care for long-term
complications in the years to come. Advances in surgical and interventional
techniques will allow us to address hemodynamic lesions and arrhythmias even more
efficiently and at lower risk. New medication for pulmonary arterial hypertension will
continue helping patients with severe exercise limitation, improving their quality of
life and outcome. As survival improves, young patients with ever more complex
disease (e.g patients with repaired hypoplastic left heart syndrome) will reach
adulthood and pose significant challenges to healthcare professionals and healthcare
systems. Expert tertiary centres will need to collaborate ever more closely with local
cardiology services to address this challenge and provide the best possible care to this
expanding population of patients.
38
Reference annotations:Papers of special note have been highlighted as:
* of interest
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39
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51
Table 1: Definition of IE according to the modified Duke criteria proposed by the
ESC Guidelines for the management of infective endocarditis.63
Major criteria
1. Blood cultures positive for IE
a. Typical microorganisms consistent with IE from 2 separate blood cultures:
• Viridans streptococci, Streptococcus gallolyticus (Streptococcus bovis), HACEK group,
Staphylococcus aureus;
• Community-acquired enterococci, in the absence of a primary focus;
b. Microorganisms consistent with IE from persistently positive blood cultures:
• ≥2 positive blood cultures of blood samples drawn >12 h apart;
• All of 3 or a majority of ≥4 separate cultures of blood (with and last samples drawn ≥1 h apart);
c. Single positive blood culture for Coxiella burnetii or phase I IgG antibody titre >1:800
2. Imaging positive for IE
a. Echocardiogram positive for IE:
• Vegetation;
• Abscess, pseudoaneurysm, intracardiac
• Valvular perforation or aneurysm;
• New partial dehiscence of prosthetic valve.
b. Abnormal activity around the site of prosthetic valve implantation detected by 18F-FDG PET/CT
(only if the prosthesis was implanted for >3 months) or radiolabelled leukocytes SPECT/CT.
c. Definite paravalvular lesions by cardiac CT.
Minor criteria
1. Predisposition such as predisposing heart condition, or injection drug use.
2. Fever as temperature >38°C.
3. Vascular phenomena (including those detected by imaging only): major arterial emboli, septic
pulmonary infarcts, infectious (mycotic) aneurysm, intracranial haemorrhage, conjunctival
haemorrhages, and Janeway’s lesions.
4. Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, rheumatoid factor.
5. Microbiological evidence: positive blood culture but does not meet a major criterion as noted
above or serological evidence of active infection with organism consistent with IE.
Interpretation
Definite IE
Pathological criteria
• Microorganisms demonstrated by culture or on histological examination of a vegetation, a
vegetation that has embolized, or an intracardiac abscess specimen; or
• Pathological lesions; vegetation or intracardiac abscess by histological examination showing active
endocarditis
Clinical criteria
• 2 major criteria; or
• 1 major criterion and 3 minor criteria; or
• 5 minor criteria
Possible IE
• 1 major criterion and 1 minor criterion; or
• 3 minor criteria
Rejected IE
• Firm alternate diagnosis; or
• Resolution of symptoms suggesting IE with antibiotic therapy for ≤4 days; or
• No pathological evidence of IE at surgery or autopsy, with antibiotic therapy for ≤4 days; or
• Does not meet criteria for possible IE, as above
IE: infective endocarditis; CT: computed tomography; FDG: fluorodeoxyglucose; HACEK: Haemophilus parainfluenzae, H.
aphrophilus, H. paraphrophilus, H. influenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella
corrodens, Kingella kingae, and K. denitrificans; Ig: immunoglobulin; PET: positron emission tomography; SPECT: single
photon emission computerized tomography
52
53
Table 2. Risk score for the stratification of patients with tetralogy of Fallot
considered for primary prevention of sudden cardiac death (implantable cardioverter
defibrillator)77
Variable
Prior palliative shunt
Inducible sustained ventricular tachycardia
QRS > 180 ms
Ventriculotomy incision
Nonsustained ventricular tachycardia
Left ventricular end-diastolic pressure > 12 mmHg
Risk score
6-12
3-5
0-2
Points attributed
2
2
1
2
2
3
Risk category
High
Intermediate
Low
54
Table 3. Types of PAH related to congenital heart disease80,81
Group A. Eisenmenger’s syndrome
Includes all systemic-to-pulmonary shunts due to large defects leading to a severe increase in PVR and
a reversed (pulmonary-to-systemic) or bidirectional shunt. Cyanosis, erythrocytosis, and multiple organ
involvement are present
Group B. PAH associated with systemic-to-pulmonary shunts
Includes moderate to large defects; PVR is mildly to moderately increased, systemic-to-pulmonary
shunting is still prevalent, whereas cyanosis at rest is not a feature. The defect could be:
 Correctable
 Non-correctable
Group C. PAH with small/coincidental defects
In cases with small defects (usually VSD <1 cm and ASD <2 cm of effective diameter assessed by
echocardiography), the clinical picture is very similar to idiopathic PAH. Closing the defect is
contraindicated.
Group D. PAH after defect correction
In these cases, CHD has been corrected but PAH is either still present immediately after surgery or has
recurred several months or years after surgery in the absence
of significant post-operative residual congenital lesions or defects that originate as a sequelae to
previous surgery.
Additional types of pulmonary vascular disease related to CHD
 Segmental pulmonary arterial hypertension: in these cases, part of the lung vasculature

develops pulmonary vascular disease, while other areas may be normally perfused or
hypoperfused
Raised PVR in Fontan patients: patients with a previous Fontan-type operation can develop
a rise in PVR, despite low pulmonary arterial pressure
PAH: pulmonary arterial hypertension; PVR: pulmonary vascular resistance; VSD: ventricular septal defect; ASD: atrial septal
defect; CHD: congenital heart disease
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a
b
RV
LV
TV
MV
LA
RV
Figure 1: A 26 year-old patient with no previous cardiac diagnosis presents with a
three-month history of progressive exertional dyspnoea. A chest x-ray shows severe
cardiomegaly. On echocardiography, congenitally corrected transposition of the great
arteries is diagnosed, with impaired systolic function of the dilated and hypertrophied
systemic right ventricle (a) and severe tricuspid regurgitation (b). RV: right ventricle
(morphological, in the systemic position); LV: left ventricle (subpulmonary); LA: left
atrium; RA: right atrium; TV: tricuspid valve; MV: mitral valve.
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a
b
Figure 2: Septic emboli in the lungs of two patients with right-sided endocarditis. In
(a), a 22 year-old patient with a restrictive perimembranous ventricular septal defect
presents with general malaise for about 3 months. On echocardiography, a mobile
vegetation attached to the VSD and septal leaflet of the tricuspid valve is seen. CT
scan reveals several septic emboli on both lungs (arrows). In (b), CT scan of a 59year-old man with a bicuspid aortic valve and previous Ross procedure, followed by
redo pulmonary valve replacement. He is admitted for endocarditis on the pulmonary
valve homograft, with an embolic abscess on the left lower lung lobe (arrow).
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a
b
c
Figure 3: A young man with a Fontan circulation for tricuspid atresia (right atrium to
pulmonary artery connection) presenting with atrial fibrillation (a); the time of onset
of this is unclear, likely several weeks. Despite the fact that the ventricular rate is not
very fast, the echocardiogram demonstrates moderate systolic impairment of the
systemic (left) ventricle. Subsequent cardiac magnetic resonance (b) and
transoesophageal echocardiogram (c) show a large clot within the right atrium.
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LPA
LPA
RPA
a
b
Figure 4: A 36 year-old patient with complex congenital heart disease and secondary
pulmonary arterial hypertension. The chest X-ray (a) shows evidence of left atrial
isomerism, dextrocardia and severe dilatation of the left PA (LPA) with mural
calcification (arrow). Cardiac magnetic resonance (b) shows a severely dilated LPA
and right pulmonary artery (RPA), with a flap of chronic dissection in the RPA (thin
grey arrow) and mural thrombus in the LPA (thick grey arrow).
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Figure 5. Two very different Eisenmenger patients.106 In (a), a 34-year-old male with
Down syndrome and Eisenmenger physiology secondary to complete atrioventricular
septal defect. There is a large inlet ventricular septal defect (thin arrow) and a large
ostium primum atrial septal defect (thick arrow) with a single atrioventricular valve.
His right ventricle is hypertrophied but not significantly dilated or impaired and is
well adapted to the systemic pulmonary pressures. He is stable in functional class 2 on
treatment with sildenafil. In (b), a 55 year-old male with Eisenmenger physiology due
to a large patent ductus arteriosus. Despite triple-combination therapy (sildenafil,
macitentan and inhaled iloprost) he is in end-stage heart failure. The right ventricle is
severely dilated and impaired and resembles that of patients with idiopathic
pulmonary arterial hypertension.
60