Hypertension

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Insights from the International Registry of Acute Aortic Dissection –
What Have We Learned?
a report by
Arturo Evangelista
Co-Director, Department of Cardiac Imaging, Hospital Vall d’Hebron, Barcelona
The International Registry of Acute Aortic Dissection (IRAD) was
monthly variations were observed only among patients aged <70 years,
established in 1996, enrolling patients at large referral centres
those with type B AAD and those without hypertension or diabetes.6
worldwide. It represents a unique opportunity to assess the current
presentation, management and outcome of acute aortic syndrome (AAS).
Clinical Presentation
The IRAD is an observational registry with more than 1,500 patients
The clinical manifestations of AAS are diverse and overlap, with a broad
enrolled at 21 tertiary centres in six countries. Collected data forms
differential diagnosis requiring a high clinical index of suspicion to pursue
included more than 290 variables analysed by the co-ordinating centre at
and aggressively treat this disorder. Patients with aortic dissection typically
the University of Michigan. The IRAD registry provides new and valuable
present a cataclysmic onset and chest and/or back pain of a blunt,
information regarding demographics, presenting symptoms and signs,
sometimes radiating nature. However, in contrast to classic teaching,
diagnostic imaging, management and outcome of AAS.
‘tearing’, ‘ripping’ or ‘migratory’ were not common descriptors of pain in
IRAD. Chest pain was significantly more common in patients with type A
Demographics and Risk Factors
than type B dissections (79 versus 63%), whereas both back pain (64
The most common predisposing factor for AAS in the IRAD series was
versus 47%) and abdominal pain (43 versus 22%) were significantly more
hypertension (72%). A history of atherosclerosis was present in 31% of
common in type B dissection. Hypertension at the time of presentation
patients and a history of cardiac surgery in 18%. In the total registry,
was more frequent in type B than in type A dissection (70 versus 36%).1
5 and 4% of cases of acute aortic dissection were thought to be related
to Marfan’s syndrome and iatrogenic causes, respectively.1
Syncope is a well-recognised symptom of acute aortic dissection, often
indicating the development of dangerous complications, such as cardiac
Analysis of young patients (<40 years of age) with dissection revealed that
tamponade, obstruction of cerebral vessels or activation of cerebral
younger patients were less likely to have a history of hypertension (34%)
receptors. Syncope was reported in 13% of patients in IRAD.7 These
or atherosclerosis (1%), but were more likely to have Marfan´s syndrome,
patients were more likely to die in the hospital (34 versus 23% of those
bicuspid aortic valve and/or prior aortic surgery.2 Thirty-two per cent of
without syncope) and were more likely to have cardiac tamponade,
patients with type A AAS were aged >70 years. Fewer elderly than
stroke, neurological deficits and a proximal dissection. Pulse deficits have
younger patients were managed surgically (64 versus 86%; p<0.0001).
also been studied in IRAD. A pulse deficit has been described in 30% of
In-hospital mortality was higher among older patients (43 versus 28%;
patients with an acute type A dissection compared with 21% of those
p=0.0006). Logistic regression analysis identified age >70 years as an
with type B dissection. These patients have a higher rate of in-hospital
independent predictor of hospital death for acute type A dissection.3
complications and mortality than those without a pulse deficit.8
Although less frequently affected by AAS (32%), women were significantly
In another study from IRAD9 the group of patients presenting with
older and were diagnosed later than men. In-hospital complications of
predominantly abdominal pain (5%) was analysed. These patients
hypotension and tamponade occurred with greater frequency in women,
experienced higher mortality than those with more typical symptoms
resulting in higher in-hospital mortality compared with men (30 versus
(10 versus 8%; p=0.02). This emphasises the atypical symptomatology in
21%; p=0.001). After adjustment for age and hypertension, mortality was
some patients and the possibility for acute aortic dissection to mimic other
higher among women than among men: type A dissection was associated
disorders such as stroke, myocardial infarction, vascular embolisation and
with a higher surgical mortality of 32% compared with 22% in men.4
abdominal pathology. Thus, diagnosis of this disease requires a high index
of suspicion of an aortic dissection in patients who have related risk factors.
Compared with those without Marfan syndrome, those with the
syndrome (5%) were considerably younger (35±12 versus 64±13 years;
occurred from 6.00am to 12.00pm compared with other time periods.
Arturo Evangelista is Co-Director of the Department of
Cardiac Imaging at Hospital Vall d’Hebron, Barcelona.
He served as President of the Spanish Working Group on
Echocardiography and Imaging Techniques from 1996 to
1999 and as President of the Spanish Working Group of
Aortic Diseases from 2003 to 2006, and is a Board
Member of the European Association of Echocardiography
(EAE). Dr Evangelista has authored over 110 articles and
10 book chapters. He graduated in medicine from
Barcelona University in 1977.
On the other hand, the frequency of AAS was significantly higher during
E: [email protected]
p<0.001) and had a higher prevalence of type A aortic dissection
(76 versus 62%; p=0.04), as well as a lower prevalence of intramural
haematoma (2 versus 11%; p=0.03).5
Like other cardiovascular conditions, AAS exhibits significant circadian and
seasonal/monthly variations. A significantly higher frequency of AAS
colder months, with a peak in January (p<0.001). However, seasonal/
© TOUCH BRIEFINGS 2008
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Diagnostic Strategies
Natural History and Prognosis
Electrocardiogram
Type A Dissection
This test should be performed on all patients as it helps to differentiate
In-hospital mortality rate was 32.5% in type A dissection patients.14 In-
pain from acute myocardial infarction, for which treatment may
hospital complications (neurological deficits, altered mental status,
include anticoagulation, in contrast to aortic dissection, where this
myocardial or mesenteric ischaemia, kidney failure, hypotension, cardiac
therapy would be contraindicated. A normal electrocardiogram (ECG)
tamponade and limb ischaemia) were increased in patients who died
was seen in one-third of patients, and ECG showed non-specific ST-
compared with survivors (p<0.05 for all). Logistic regression identified the
and T-wave changes in 42%, ischaemic changes in 15% and evidence
following presenting variables as predictors of death: age >70 years (OR
of an acute myocardial infarction in 5% of patients with an ascending
1.70), abrupt onset of chest pain (OR 2.50) hypotension/shock/
aortic dissection.
tamponade (OR 2.97), kidney failure (OR 4.77), pulse deficit (OR 2.03)
and abnormal ECG (OR 1.77); area under receiver operating curve 0.74.
Chest X-ray
This analysis provides a useful and simple bedside risk prediction tool that
A routine chest X-ray is abnormal in 60–90% of cases with suspected
could be used by physicians for determining the prognosis of patients
aortic dissection. However, 12% of patients have a completely normal
with acute type A AAS.
chest X-ray.1 Because of the limited sensitivity of this method, additional
imaging studies are required in all patients.
Type B Dissection
Acute aortic dissection affecting the descending aorta is less lethal than
Imaging Studies
type A dissection. Patients with uncomplicated type B dissection have a
During the IRAD period a shift was shown from an invasive (aortography)
30-day mortality of 10.5%.15 However, patients who develop ischaemic
to a non-invasive diagnostic strategy for evaluating suspected thoracic
complications such as renal failure, visceral ischaemia or contained rupture
aortic dissections. Most patients require multiple imaging studies to
often require urgent aortic repair, which carries a mortality of 20% by day
diagnose and characterise aortic dissection. In IRAD,10 the initial study was
two and 25% by day 30. Similar to type A dissection, advanced age,
computed tomography (CT) in 61%, echocardiography in 33%,
rupture, shock and malperfusion are important independent predictors of
aortography in 4% and magnetic resonance imaging (MRI) in only 2%. The
early mortality. A risk prediction model with control for age and gender
mean number of studies performed per patient was 1.8. In type A AAS,
showed hypotension/shock (OR 23.8), absence of chest/back pain on
transoesophageal echocardiography was the most commonly used
presentation (OR 3.5) and branch vessel involvement (OR 2.9) – collectively
technique (79%), mainly in US sites. Imaging techniques revealed aortic
named ‘the deadly triad’ – to be independent predictors of in-hospital
regurgitation in 62%, pericardial effusion in 46% and coronary artery
death.15 A subanalysis in elderly patients16 (>70 years) showed that
involvement in 14%. A proximal intimal tear was identified in the aortic
hypotension/shock was more common and malperfusion of a visceral
root in 39% of patients, in the ascending aorta in 55% and in the
organ less frequent among the elderly cohort compared with the younger
aortic arch in 4%. For the diagnosis of acute aortic dissection, all four
patients (16 versus 10%; p=0.07). A classification tree identified that
diagnostic tests (CT, transoesophageal echocardiography, MRI and
elderly patients with hypotension/shock had the highest risk of death
aortography) demonstrate a high diagnostic sensitivity. However, the
(56%). In the absence of this, any branch vessel involvement was
false-negative rate is still considerable, such that the diagnosis cannot be
associated with the highest mortality rate (29%), followed by the presence
excluded confidently on the basis of a single test. Another imaging test is
of peri-aortic haematoma (11%). In contrast, elderly patients without any
strongly recommended when the diagnosis is highly suspected clinically.
of these three risk factors had an extremely low mortality rate (1.3%).
IRAD contributed new imaging information that aids diagnostic accuracy.
Variants
10
Maximum aortic diameters in acute type A dissection were <55mm in
59% of cases and <50mm in 40% of cases.11 Independent predictors of
Intramural Haematoma
dissection at diameters <55mm were history of hypertension and age.
Although the clinical manifestations of intramural haematoma are similar
Marfan’s syndrome patients were more likely to dissect at larger diameters
to those of acute aortic dissection, the former tends to be more of a
(odds ratio [OR] 14.3). In-hospital mortality was not related to aortic size.
segmental process; therefore, radiation of pain, pulse deficits and aortic
valve insufficiency are less common.17 The natural history of acute IMH
Peri-aortic haematoma was present in 23% of cases (26% in type A and
continues to be debated. In patients with symptoms consistent with
19% in type B) and implied significantly greater mortality (33 versus
acute aortic dissection, acute IMH accounts for 5–20% of cases; in IRAD
20%; p<0.001).12 A multivariate model demonstrated peri-aortic
it accounted for 5.7% of AAS. This cohort tended to be older (69 versus
haematomas to be an independent predictor of mortality in patients with
62 years of age; p<0.001) and more likely to have distal aortic
aortic dissections (OR 1.71).
involvement (60 versus 35%; p<0.0001). Overall mortality was similar to
that of classic dissection (21 versus 24%). The analysis demonstrated an
Finally, a recent study showed that transoesophageal echocardiography
association between increasing hospital mortality and the proximity of
provides prognostic information in type A AAS. Independent predictors
IMH to the aortic valve, regardless of medical or surgical treatment.
13
of mortality were cardiac tamponade (OR 2.7), whereas dissection flap
confined to the ascending aorta (OR 0.2) and false lumen thrombosis
Treatment
(OR 0.15) were protective. When only the surgically treated patients
One of the important contributions of IRAD is to show the current
were considered, peri-aortic haematoma was an independent predictor
management and outcome of AAS. Type A acute aortic dissection was
of mortality.
treated surgically in 81.7% of cases.18 The reasons for medical treatment
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EUROPEAN CARDIOLOGY
ESH_ad.qxp
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European Society of Hypertension
ESH
www.eshonline.org
Scientific Council 2007–2009
PRESIDENT
VICE PRESIDENT
SECRETARY
TREASURER
OFFICER AT LARGE
IMMEDIATE
PAST PRESIDENT
Stéphane Laurent
(France)
Harry A.J. Struijker Boudier
(The Netherlands)
Krzysztof Narkiewicz
(Poland)
Michel Burnier
(Switzerland)
Josep Redon
(Spain)
Sverre E. Kjeldsen
(Norway)
COUNCIL MEMBERS
Ettore Ambrosioni (Italy), Antonio Coca (Spain), Anna Dominiczak
(United Kingdom), Athanasios J. Manolis (Greece), Peter Nilsson (Sweden),
Michael Hecht Olsen (Denmark), Roland E. Schmieder (Germany),
Margus Viigimaa (Estonia)
EX-OFFICIO COUNCIL MEMBER
Lars H. Lindholm (Sweden) — ISH Represenative
Robert Fagard (Belgium) — ESC Representative
EXECUTIVE OFFICERS
Giuseppe Mancia (Italy) — Chairman, Educational Committee
Enrico Agabiti Rosei (Italy)— Coordinator, Working Group
Renata Cifkova (Czech Republic) — Secretary, Educational Committee
Serap Erdine (Turkey) — ESH representative to EBAC
Selected activities of the European Society of Hypertension
’ Annual Meetings
Œ 2009 — Milan, June 12–16
Œ 2010 — Oslo, June 18–22
Œ 2011 — Milan, June 17–21
Œ 2012 — London, April 26–30
Œ 2013 — Milan, June 14–18
Œ 2014 — Athens (as a joint ISH/ESH meeting)
Œ 2015 — Milan
Milan, June 12–16, 2009
Further details available at
www.esh2009.com
’ 2007 ESH/ESC Guidelines on management of hypertension
’ European Hypertension Specialist Programme
’ ESH Hypertension Excellence Centres
Important dates
’ Deadline for submission of abstracts:
January 15, 2009
’ Deadline for early registration:
March 31, 2009
’ Deadline for pre-registration:
May 11, 2009
’ Hotel reservation:
May 29, 2009
www.eshonline.org
’ Working Groups
’ ESH Summer School — a week of intensive training
in hypertension research for young investigators
’ Advanced Courses — a week of intensive training
in clinical hypertension
’ ESH Teaching Faculty
’ Research Grants — ESH Fellowships
’ ESH Newsletters — a periodical
experts’ updates on hypertension
management
’ ESH textbook 2008
’ www.eshonline.org — the source
of trusted hypertension-related
information and high-quality
educational content
Learn about the ESH organization and all it has to offer
Download the new 2007 hypertension guidelines
Use the educational resources including 2007 guidelines slide set
Read highlights of the annual meetings of ESH and other societies
Watch webcast teaching seminars
Read the ESH newsletter, a concise, comprehensive overview of treatment issues
Link to medical journals and key international conferences
Read and review clinical guidelines
Visit the Clinical Hypertension Specialists section
My Simple Guide to High Blood Pressure — a patient education resource
provided by the ESH. This module provides basic and detailed information about all aspects of
high blood pressure and its treatment, and it can be accessed through the ESH website or through
www.my-hypertension.org. Encourage your patients and their families to use this resource,
and to download and print the tip sheets for lifestyle modifications and for monitoring their blood
pressure levels and medications. Many useful links are also provided.
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in the remaining patients were advanced age, severe co-morbid illness or
dismal in-hospital prognosis, two-thirds of these patients are alive at
refusal of any surgical intervention. The ascending aorta was replaced
three years if they survive the initial hospitalisation. Thus, they deserve
in 92% of patients, the partial arch in 23.2% and the complete arch in
and probably benefit from ongoing medical therapy. On the other hand,
12%. The aortic valve was replaced in 23% of cases. A composite aortic
three-year survival in patients presenting with type B acute aortic
valve graft was used in 14% of cases. The mortality in surgically treated
dissection was 78% with medical treatment, 83% with surgical
patients was 25%. In unstable patients it was 31.4% compared with
treatment and 76% with endovascular therapy.22 Independent
16.7% in stable patients. A model with intraoperative haemodynamic
predictors of follow-up mortality included female gender, a history of
and surgical variables showed that intraoperative hypotension, a right
prior aortic aneurysm, a history of atherosclerosis, in-hospital renal
ventricle dysfunction at surgery and the need to perform coronary
failure, pleural effusion on chest radiograph and in-hospital
revascularisation were predictors of surgical death.19
hypotension/shock. When imaging information was included, partial
thrombosis of the false lumen, present in one-third of patients, was the
At present, endovascular interventions or surgical repair have no proven
strongest independent predictor of post-discharge mortality. The risk of
superiority over medical treatment in stable patients with type B AAS. In the
death in these patients was increased by a factor of 2.7 in comparison
IRAD series, 73% of patients were managed medically. In-hospital mortality
with patients without partial false lumen thrombosis.23 Some possible
for these patients was 10%.
Twelve per cent of acute type B aortic
explanations for this based on the haemokinetics of false lumen flow
dissections were managed with endovascular therapy; this was similar to the
were analysed. Involvement of the aortic arch was addressed in a recent
15
number of patients treated with surgery (15%). Mortality in patients treated
study.24 It was found that 25% of patients with AAS type B had
surgically was 29%.20 Factors associated with increased surgical mortality
involvement of the aortic arch on cross-sectional imaging. Of these, the
based on univariate analysis were pre-operative coma or altered
arch was the site of the intimal tear in at least 37%. Aortic arch
conciousness, partial thrombosis of the false lumen, evidence of peri-aortic
involvement in patients presenting with AAS type B did not appear to
haematoma on diagnostic imaging, descending aortic diameter >60mm,
increase the risk of either in-hospital or follow-up mortality.
right ventricle dysfunction at surgery and shorter time from the onset of
symptoms to surgery. The two independent predictors of surgical mortality
Conclusions
were age >70 years (OR 4.3) and pre-operative shock/hypotension (OR 6.1).
Much has been learned about the risk factors, clinical presentation,
diagnosis and management of acute aortic dissection from the IRAD
Long-term Follow-up
registry. However, despite recent advances in diagnostic and therapeutic
In patients with type A AAS who survive to hospital discharge, predictors
techniques, mortality in acute aortic syndromes remains high. This
of follow-up all reflect patient history variables as opposed to in-hospital
observation might reflect both a logistic problem and the inadequacy of
parameters or in-hospital complications, which may be explained by the
the surgical approach in the attempt to treat patients in extreme
successful in-hospital treatment of the acute dissection.21 Survival for
conditions. IRAD data highlight the notion that a stable clinical status in
patients treated with surgery was 91% at three years and 69% without
acute proximal dissection heralds a positive surgical outcome. Although
surgery. Predictors of mortality were a history of atherosclerosis and
the time interval between symptom onset and surgical intervention
previous cardiac surgery (OR 2.1 and 2.5, respectively, as independent
remains a major factor in terms of mortality, cardiologists should improve
predictors of mortality). This study sheds some light on the medically
diagnostic pathways and vascular staging in AAS and set up referral
treated cohort once they survive to hospital discharge. In contrast to a
networks together with allocation systems. ■
1.
2.
3.
4.
5.
6.
7.
8.
9.
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EUROPEAN CARDIOLOGY