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Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New Insights Into an Old Disease. JAMA. 2000;283(7):897–903. doi:10.1001/jama.283.7.897
Author Affiliations: University of Michigan, Ann Arbor (Drs Hagan, Das, Armstrong, Deeb, and Eagle, Messrs Bruckman and Karavite, and Ms Russman); Massachusetts General Hospital, Boston (Dr Isselbacher), and University of Massachusetts, Worcester (Dr Pape and Ms Gaca); Hospital General Universitari Vall d'Hebron, Barcelona (Dr Evangelista), and Hospital 12 de Octubre, Madrid (Drs Marcos y Robles and Llovet), Spain; University Hospital S Orsola, Bologna, Italy (Dr Fattori); University of Tokyo, Tokyo, Japan (Dr Suzuki); Mayo Clinic, Rochester, Minn (Drs Oh, Moore, and Malouf); University Hospital Eppendorf, Hamburg (Dr Nienaber), Robert-Bosch Krankenhaus, Stuttgart (Drs Sechtem and Lenferink), and University of Cologne, Cologne (Drs Deutsch and Diedrichs), Germany; and Hadassah University Hospital, Jerusalem, Israel (Dr Gilon).
Context Acute aortic dissection is a life-threatening medical emergency associated
with high rates of morbidity and mortality. Data are limited regarding the
effect of recent imaging and therapeutic advances on patient care and outcomes
in this setting.
Objective To assess the presentation, management, and outcomes of acute aortic
Design Case series with patients enrolled between January 1996 and December
1998. Data were collected at presentation and by physician review of hospital
Setting The International Registry of Acute Aortic Dissection, consisting of
12 international referral centers.
Participants A total of 464 patients (mean age, 63 years; 65.3% male), 62.3% of whom
had type A dissection.
Main Outcome Measures Presenting history, physical findings, management, and mortality, as
assessed by history and physician review of hospital records.
Results While sudden onset of severe sharp pain was the single most common presenting
complaint, the clinical presentation was diverse. Classic physical findings
such as aortic regurgitation and pulse deficit were noted in only 31.6% and
15.1% of patients, respectively, and initial chest radiograph and electrocardiogram
were frequently not helpful (no abnormalities were noted in 12.4% and 31.3%
of patients, respectively). Computed tomography was the initial imaging modality
used in 61.1%. Overall in-hospital mortality was 27.4%. Mortality of patients
with type A dissection managed surgically was 26%; among those not receiving
surgery (typically because of advanced age and comorbidity), mortality was
58%. Mortality of patients with type B dissection treated medically was 10.7%.
Surgery was performed in 20% of patients with type B dissection; mortality
in this group was 31.4%.
Conclusions Acute aortic dissection presents with a wide range of manifestations,
and classic findings are often absent. A high clinical index of suspicion
is necessary. Despite recent advances, in-hospital mortality rates remain
high. Our data support the need for continued improvement in prevention, diagnosis,
and management of acute aortic dissection.
On 25 October 1760 George II, then 76, rose at his normal
hour of 6 AM, called as usual for his chocolate, and repaired to the closet-stool.
The German valet de chambre heard a noise, memorably described as ‘louder
than the royal wind', and then a groan; he ran in and found the King lying
on the floor, having cut his face in falling. Mr. Andrews, surgeon of the
household, was called and bled his Majesty but in vain, as no sign of life
was observed from the time of his fall. At necropsy the next day Dr. Nicholls,
physician to his late Majesty, found the pericardium distended with a pint
of coagulated blood, probably from an orifice in the right ventricle, and
a transverse fissure on the inner side of the ascending aorta 3.75 cm long,
through which blood had recently passed in its external coat to form a raised
ecchymosis, this appearance being interpreted as an incipient aneurysm of
the aorta. 1
Disease is very old, and nothing about it has
changed. It is we who change as we learn to recognize what was formerly imperceptible.—Jean
Acute aortic dissection is a challenging clinical emergency first described
by Morgagni more than 200 years ago.2 In 1958,
Hirst et al3 reviewed 505 patients with the
condition, highlighting the high mortality rate and the infrequency of antemortem
diagnosis. Prior to the introduction of cardiopulmonary bypass in the mid
1950s, surgical options were severely limited.4
Since Debakey first reported surgical repair of a thoracic aortic aneurysm,
management techniques have steadily advanced.5-14
Recently, percutaneous fenestration and/or stent placement have been used
in select patients.15-19
Similarly, diagnostic imaging modalities, including computed tomography, transesophageal
echocardiography, and magnetic resonance imaging, have been developed and
are widely available.20-25
Aortic dissection is the most common acute aortic condition requiring
urgent surgical therapy.26-29
Separation of the layers within the aortic wall characterizes dissection.
Blood enters the intima-media space with further propagation of the dissection.
Typically, 1 or more tears in the intimal layer allow communication between
the 2 lumens. Intramural hematoma without an intimal tear is a distinct pathological
lesion that is being observed with increasing frequency. Presenting features
are similar, and progression to dissection may occur.30-32
While the initiating event is unknown, most patients have a structural abnormality
of the arterial wall and/or systemic hypertension.3,33-35
Classification of aortic dissection is based on anatomical location
and time from onset. Stanford type A dissections involve the ascending aorta
and type B dissections occur distal to the left subclavian artery.36 The 14-day period after onset has been designated
the acute phase, because morbidity and mortality rates are highest and surviving
patients typically stabilize during this time.
Because presenting clinical features are diverse and serious complications
occur rapidly, antemortem diagnosis has proven difficult.3,37,38
One would predict that the advent of modern imaging combined with progress
in both surgical and nonsurgical therapy should result in improved outcomes.
Little is known about the effect of these developments. Therefore, The International
Registry of Acute Aortic Dissection (IRAD) was established in 1996, enrolling
patients at large referral centers, to assess the current presentation, management,
and outcomes of acute aortic dissection.
Twelve large referral centers in 6 countries are participating in the
registry. All patients with acute aortic dissection were enrolled beginning
January 1, 1996. Patients were identified at presentation or by searching
hospital discharge diagnosis records and surgical and echocardiography laboratory
databases. Diagnosis was based on history, imaging study findings, visualization
at surgery, and/or postmortem examination. Patients with aortic disruption
secondary to trauma were excluded.
A questionnaire of 290 variables, defined according to standard definitions,
including demographics, history, physical findings, management, imaging studies,
and outcomes, was developed by IRAD investigators.39
Data were collected at presentation or by physician review of hospital records
and were forwarded to the IRAD Coordinating Center at The University of Michigan.
Forms were reviewed for clinical face validity and analytical internal validity.
External validation was performed through a random (5%) field selection and
error audit. More than 33% of patient report forms were re-reviewed for validation
by each site.
Data analysis was performed using statistical analysis software. Univariate
analyses were used to compare frequency, proportion, or distribution of demographic
and comorbidity variables between samples. χ2 Cross-tabulations, t tests, or nonparametric Wilcoxon rank sum tests were
applied as appropriate. To determine a trend across groups, regardless of
condition, the extended Mantel-Haenszel correlation statistic at 1 df was used. Categorical modeling was used to test statistical trends
and associations using the likelihood ratio test for model determination.
Models were selected using likelihood ratio tests, with a significance level
of .05. Corrections due to multiple comparisons were used to determine appropriate
levels of significance.
As of December 31, 1998, 464 patients have been enrolled (Table 1). Two thirds of those patients were male. Mean age of all
patients was 63.1 years (95% confidence interval, 61.8-64.4 years). Type A
dissection was identified in 62.3% of patients. Patients with type B dissection
were, on average, older (P<.001). A history of
cardiac surgery was present in 83 patients (17.9%). Iatrogenic dissection
was reported in 20 patients (4.3%). Sixty percent of patients initially presented
to an outside hospital and were referred to IRAD centers for continued management.
A history of hypertension was elicited in 72.1% of all patients. Marfan syndrome
was present in 4.9% of all patients (mean age, 36 years; range, 13-52 years).
Severe pain was the most common presenting symptom, and 84.8% of patients
recalled abrupt onset (Table 2).
The majority of patients complained of chest pain (72.7%). Anterior chest
pain was typical in patients with type A dissection, whereas patients with
type B dissection more often experienced pain in the back and abdomen, although
there was substantial overlap (P<.001). Of note,
pain was described as sharp more often than tearing or ripping. Hypertension
at initial presentation was more common among patients with type B dissection
(70.1% vs 35.7%, P<.001). One in 4 patients with
type A dissection had an initial systolic blood pressure below 100 mm Hg.
When documented, a pulse deficit was noted more often in patients with type
A dissection (P = .006). Most patients who presented
with stroke also gave a history of pain. Among patients with type A dissection,
12.7% presented with syncope, and most did not have other neurological findings.
Chest radiography showed absence of mediastinal widening in 37.4% of
patients with type A dissection and an abnormal aortic contour was noted in
the minority of those patients (Table 3). Chest radiography showed both absence of mediastinal widening
and absence of abnormal aortic contour in 21.3% of all patients. No chest
radiography abnormality was noted in 12.4% of patients. The 12-lead electrocardiogram
most frequently showed nonspecific abnormalities; results were normal for
31.3% of patients.
Most patients had multiple imaging studies performed (Table 3). Computed tomography was more often the initial study tool,
particularly in patients with type B dissection. Aortography and magnetic
resonance imaging were rarely used initially. Aortic insufficiency was noted
by imaging in half of patients with type A dissection. Intramural hematoma
was noted in 46 patients and two thirds of these had type B dissection (P<.001).
Of 289 patients with type A dissection, 72% were managed surgically
(Table 4). Surgery was not performed
in 28% of patients with type A dissection because of advanced age, comorbidity,
patient refusal, intramural hematoma, and death prior to planned surgery.
Surgical therapies in ascending aortic dissection included coro nary artery
bypass in 33 patients, aortic valve repair/replacement in 34 patients, and
aortic arch repair in 39 patients (21 partial; 18 complete). Of 175 patients
with type B dissection, 20% underwent surgical therapy. Percutaneous fenestration
and/or stenting was performed in 20 patients (4.3%). Median hospital stay
among surviving patients was 16 days and did not differ between dissection
types (P = .19).
Overall in-hospital mortality was 27.4%. Highest mortality occurred
in patients with type A dissection not receiving surgery (58.0%), in contrast
to surgically treated patients with type A dissection (26%). Patients with
type B dissection treated medically had the lowest mortality (10.7%). However,
mortality for patients with type B dissection who underwent surgery was 31.4%.
Mortality was highest within the first 7 days of presentation (Figure 1). When reported, the most common causes of death among
patients with type A dissection were aortic rupture or cardiac tamponade (41.6%)
and visceral ischemia (13.9%). Aortic rupture (38.5%) and visceral ischemia
(15.4%) were the most common causes of death in patients with type B dissection.
Female patients tended to be older (67.9 vs 60.6 years, P<.001) and had a higher mortality rate than males (33.5% vs 24.1%, P<.001). Patients with intramural hematoma had mortality
rates similar to those with intimal tears. Among 46 patients (10% of total
sample) with intramural hematoma, 17 were type A and 29 type B. Among type
A patients, 9 received surgical therapy, of whom 4 died, and 8 received medical
therapy, of whom 4 died. Of type B patients, 24 were managed medically resulting
in 4 hospital deaths, and 5 required surgery, resulting in 1 death.
Acute aortic dissection may be uncommon, but complications occur often
and early, and the outcome is frequently fatal.3,40-42
Since dissection is a dynamic process that may occur anywhere within the aorta,
the clinical spectrum of presentation is broad. Symptoms may mimic more common
disorders such as myocardial ischemia or stroke, and physical findings may
be absent or suggestive of a diverse range of other conditions.3,38,43-45
Therefore, dissection is often difficult to diagnose, and a high clinical
index of suspicion is mandatory. As recently as a decade ago, a large referral
center reported on a series of patients in whom the diagnosis was frequently
missed on initial evaluation (38%) and first established in 28% of patients
at postmortem examination.37 Although clinicians
today are better equipped to deal with the complex threat posed by aortic
dissection, mortality rates remain high.
The typical patient in the IRAD registry is a male in his seventh decade
with a history of hypertension who presents with abrupt onset of chest pain.
A history of hypertension, which is considered the most common predisposing
factor for aortic dissection, was present in more than 70% of patients.3,46
In contrast to classic teaching, tearing or ripping were not the characteristic
descriptors of pain. While most clinicians would appropriately associate these
terms with aortic dissection, our patients were more likely to describe their
pain as sharp in nature. Migratory pain has been described as characteristic
but was noted in only 16% of patients in IRAD.47
Syncope occurred in more than 12% of patients with type A dissection,
and 10 (2.2%) of these patients did not have pain or other neurological findings.
Thus, aortic dissection should be considered in the differential diagnosis
of syncope, even in the absence of pain. While the physical examination may
provide valuable clues to the diagnosis of aortic dissection, typical signs
were often absent. For example, pulse deficit, which was reported previously
in up to 50% of patients with type A dissection, was recorded in less than
20% of patients in IRAD. The murmur of aortic regurgitation, reported previously
in approximately two thirds of patients, was documented in 44% of patients
with type A dissection.37,47
Earlier studies describe the value of the abnormal chest radiography
findings in the evaluation of suspected aortic dissection.46,48
While chest radiography may be helpful, a substantial number of patients did
not have evidence of widened mediastinum or abnormal aortic contour.
The incidence of aortic dissection has been estimated at from 5 to 30
per 1 million people per year, and the incidence of acute myocardial infarction
in the United States has been estimated at 4400 per 1 million per year.28,29,49 Differentiating aortic
dissection from myocardial ischemia is a common clinical dilemma, and because
the therapeutic strategy is very dissimilar, rapid, accurate diagnosis is
dissection and myocardial infarction may occur concomitantly. Normal electrocardiogram
findings have been touted as a marker to move clinicians away from a diagnosis
of myocardial ischemia or infarction and toward dissection.34,47
Normal electrocardiogram findings were present in less than a third of our
patients, suggesting that this test was not especially helpful in the differential
The choice of initial imaging modality may reflect availability rather
than preference. Although transesophageal echocardiography is accurate and
can be performed quickly at the bedside with minimal risk, computed tomography
was the most common initial assessment performed. Despite recent reports of
high sensitivity and specificity of magnetic resonance imaging, it was rarely
used as a first diagnostic imaging method.24,25
Availability, time delay, restricted ability to monitor patients during imaging,
and incompatibility with implanted metal devices are likely explanations for
its limited use. Aortography, previously the criterion standard, was used
infrequently, and rarely as the initial study.
Despite improved diagnostic and therapeutic techniques, overall in-hospital
mortality for acute aortic dissection was 27.4%. As expected, highest mortality
occurred early after symptom onset, emphasizing the urgency of diagnosis and
institution of appropriate therapy. A minority of patients with type A dissection
did not receive surgery, primarily because of advanced age and comorbidity.
Accordingly, these patients had the poorest outcome, with more than half dying
in the hospital. Patients with type B dissection who underwent surgery also
had a high mortality rate, mainly because of aortic rupture and complications
of visceral ischemia. The majority of patients with type B dissection had
an uneventful hospital course and were managed medically. Patients with intramural
hematoma had similar outcome to those with classic dissection.
While the IRAD experience is the largest study of aortic dissection
in recent years, there are limitations. Since high-volume referral sites were
selected, the data may not be applicable to the general community. Most patients
were white. Many patients with aortic dissection die before presentation to
the hospital or prior to diagnosis. We studied only patients who were alive
at the time of diagnosis. Since some data were gathered by chart review, the
limitations of these methods apply. However, data were rigorously reviewed,
and we did not impute for any missing variables. The diagnosis remains unconfirmed
by surgical or pathologic correlation in medically managed survivors. However,
because patients were evaluated at referral centers and had presentations
and imaging studies consistent with acute dissection, we do not believe that
this is a significant limitation. While the outcome data are striking, inferences
should be made with caution. Patient survival to hospitalization varies, and
the choice of therapy was influenced by many factors, including age and condition
of the patient.
Acute aortic dissection is uncommon, but complications develop rapidly
and the outcome is often fatal. The typical presentation is characterized
by acute onset of severe pain. However, clinical manifestations are diverse,
and what were previously considered to be classic symptoms and signs are often
absent. Therefore, a high clinical index of suspicion is necessary.
Despite significant advances in diagnostic and therapeutic techniques,
morbidity and mortality rates remain high. Although it is clear that during
the past 2 centuries much progress has been made, these data support the need
for continued improvements in our ability to understand, diagnose, and manage
this devastating condition.