Intravascular ultrasound of the elastic pulmonary arteries: a new approach for the evaluation of primary pulmonary hypertension.
ABSTRACT To assess the structural and functional characteristics of pulmonary arteries by intravascular ultrasound (IVUS) in the setting of primary pulmonary hypertension, and to correlate the ultrasound findings with haemodynamic variables and mortality at follow up.
Prospective observational study.
University hospital (tertiary referral centre).
20 consecutive patients with primary pulmonary hypertension (16 female; mean (SD) age, 39 (14) years).
Cardiac catheterisation and simultaneous IVUS of pulmonary artery branches at baseline and after infusion of epoprostenol.
33 pulmonary arteries with a mean diameter of 3.91 (0.80) mm were imaged, and wall thickening was observed in all cases, 64% being eccentric. Mean wall thickness was 0.37 (0.13) mm, percentage wall area 31.0 (9.3)%, pulsatility 14.6 (4.8)%, and pulmonary/elastic strain index 449 (174) mm Hg. No correlation was observed between IVUS findings and haemodynamic variables. Epoprostenol infusion increased pulsatility by 53% and decreased the pulmonary/elastic strain index by 41% (p = 0.0001), irrespective of haemodynamic changes. At 18 (12) months follow up, nine patients had died. A reduced pulsatility and an increased pulmonary/elastic strain index were associated with increased mortality at follow up (12.0 (4.4)% v 16.4 (4.4)%, p = 0.03; 369 (67) v 546 (216) mm Hg, p = 0.02).
IVUS demonstrated pulmonary artery wall abnormalities in all patients with primary pulmonary hypertension, mostly eccentric. The severity of the changes did not correlate with haemodynamic variables, and epoprostenol improved pulmonary vessel stiffness. There was an association between impaired pulmonary artery functional state as determined by IVUS and mortality at follow up.
- SourceAvailable from: Juan Grignola[Show abstract] [Hide abstract]
ABSTRACT: Exercise capacity is impaired in pulmonary arterial hypertension (PAH). We hypothesized that cardiovascular reserve abnormalities would be associated with impaired hemodynamic response to pharmacological stress and worse outcome in PAH. Eighteen PAH patients (p) group 1 NYHA class II/III and ten controls underwent simultaneous right cardiac catheterization and intravascular ultrasound at rest and during low dose-dobutamine (10 mcg/kg/min) with trendelenburg (DST). We estimated cardiac output (CO), pulmonary vascular resistance (PVR) and capacitance (PC), and PA elastic modulus (EM). We concomitantly measured tricuspid annular plane systolic excursion (TAPSE), RV myocardial peak systolic velocity (Sm) and isovolumic myocardial acceleration (IVA) in PAH patients. Based on the rounded mean + 2 SD of the increase in mPAP in our healthy control group during DST (2.8 + 1.8 mm Hg), PAH p were divided into two groups according to mean PA pressure (mPAP) response during DST, 1: DeltamPAP >5 mm Hg and 2: DeltamPAP <=5 mm Hg. Cardiovascular reserve was estimated as the change (delta, Delta) during DST compared with rest, including DeltamPAP with respect to DeltaCO (DeltamPAP/DeltaCO). All patients were prospectively followed up for 2 years. PAH p showed significant lower heart rate and CO increase than controls during DST, with a significant mPAP and pulse PAP increase and higher DeltamPAP/DeltaCO (p < 0.05). Neither hemodynamic, IVUS and echocardiographic data were different between both PAH groups at rest. In group 1, DST caused a higher DeltaEM, DeltamPAP/DeltaCO, DeltaPVR, and DeltaTAPSE than group 2, with a lower IVA increase and a negative DeltaSV (p < 0.05). TAPSE correlated with mPAP and RVP (p < 0.05) and, IVA and Sm correlated with CO (p < 0.05). DeltaEM correlated with DeltamPAP and DeltaIVA with DeltaCO (p < 0.05). There were two deaths/pulmonary transplantations in group 1 and one death in group 2 during the follow-up (p > 0.05). Pulmonary vascular reserve and RV systolic reserve are significantly impaired in patients with PAH. The lower recruitable cardiovascular reserve is significantly related to a worse hemodynamic response to DST and it could be associated with a poor clinical outcome.BMC Pulmonary Medicine 04/2014; 14(1):69. · 2.76 Impact Factor
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ABSTRACT: Recently, there has been much debate about pulmonary hypertension due to modern therapeutic options available. Arterial hypertension is frequently associated with stiffening of a given artery. The aim of the present review is to present clinical imaging methods for the evaluation of the function and stiffness of the pulmonary artery. Orv. Hetil., 154(49), 1931-1933.Orvosi Hetilap 12/2013; 154(49):1931-3.
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ABSTRACT: Abstract Objective: To find out the relation between endothelial microparticles (EMPs), pulmonary arterial stiffness and thickness of pulmonary artery intima media to determine the prognosis of Eisenmenger syndrome and their correlation with echocardiographic and hemodynamic parameters. Methods: Sixteen patients with Eisenmenger syndrome and 37 control patients were included. Electron microparticles levels, angiographic and echocardiographic findings were compared. Results: Thickness of pulmonary arterial intima media and systolic and diastolic diameters of pulmonary artery were found significant in the patient group. CD144 and CD146 EMP values of patient group were statistically high. However, there was not any significant difference in pulmonary arterial strain, elasticity and stiffness. Positive significant relationship was found between pulmonary artery intima media thickness and CD144 in patient group. But there was not any significance between CD 146 and pulmonary artery intimamedia thickness. Conclusions: Invasive methods remain as the gold standard for pulmonary hypertension diagnosis, follow-up and treatment, but it is risky and can even be fatal. Our study showed that EMPs, thickness of pulmonary artery intima media and pulmonary stiffness could be novel noninvasive modalities for the follow-up pulmonary hypertensive patients.Biomarkers 04/2014; · 1.88 Impact Factor
Intravascular ultrasound of the elastic pulmonary arteries:
a new approach for the evaluation of primary pulmonary
J Rodés-Cabau, E Domingo, A Román, J Majó, B Lara, F Padilla, I Anívarro, J Angel,
J C Tardif, J Soler-Soler
Objective: To assess the structural and functional characteristics of pulmonary arteries by intravascular
ultrasound (IVUS) in the setting of primary pulmonary hypertension, and to correlate the ultrasound
findings with haemodynamic variables and mortality at follow up.
Design: Prospective observational study.
Setting: University hospital (tertiary referral centre).
Patients: 20 consecutive patients with primary pulmonary hypertension (16 female; mean (SD) age,
39 (14) years).
Methods: Cardiac catheterisation and simultaneous IVUS of pulmonary artery branches at baseline
and after infusion of epoprostenol.
Results: 33 pulmonary arteries with a mean diameter of 3.91 (0.80) mm were imaged, and wall
thickening was observed in all cases, 64% being eccentric. Mean wall thickness was 0.37 (0.13) mm,
percentage wall area 31.0 (9.3)%, pulsatility 14.6 (4.8)%, and pulmonary/elastic strain index 449
(174) mm Hg. No correlation was observed between IVUS findings and haemodynamic variables.
Epoprostenol infusion increased pulsatility by 53% and decreased the pulmonary/elastic strain index
by 41% (p = 0.0001), irrespective of haemodynamic changes. At 18 (12) months follow up, nine
patients had died. A reduced pulsatility and an increased pulmonary/elastic strain index were associ-
ated with increased mortality at follow up (12.0 (4.4)% v 16.4 (4.4)%, p = 0.03; 369 (67) v 546
(216) mm Hg, p = 0.02).
Conclusions: IVUS demonstrated pulmonary artery wall abnormalities in all patients with primary pul-
monary hypertension, mostly eccentric. The severity of the changes did not correlate with
haemodynamic variables, and epoprostenol improved pulmonary vessel stiffness. There was an associ-
ation between impaired pulmonary artery functional state as determined by IVUS and mortality at fol-
and death.1Median survival is 2.8 years from the time of diag-
nosis, and mortality reaches 65% at three years of follow up.2
Calcium channel blockers, warfarin, and prostacyclin have
improved the prognosis, but the three year mortality has
remained as high as 50%.3
pulmonary hypertension is based on clinical and haemody-
namic data, and prognosis is determined by the alterations in
haemodynamic variables (mean pulmonary artery pressure,
cardiac output, mean right atrial pressure).
The assessment of pulmonary artery morphology in
primary pulmonary hypertension has been limited to pulmo-
nary angiography and to the histological study of lung
samples obtained at biopsy. Pulmonary angiography, which is
not free of complications in these cases, only shows the vessel
lumen and provides no information about vessel wall
abnormalities. Histological evaluation of lung biopsies pro-
vides a valuable quantitative and qualitative description of the
pulmonary wall changes, but remains a static in vitro
examination without functional assessment and requires a
thoracotomy. Intravascular ultrasound (IVUS) has been
validated as a reliable method for describing pulmonary vessel
wall morphology and pulmonary artery pulsatility.4 5It is a
unique form of exploration that can provide a simultaneous
morphological and functional evaluation of the pulmonary
vasculature. However, pulmonary artery ultrasound imaging
rimary pulmonary hypertension is a life threatening dis-
ease characterised by a progressive increase in pulmonary
blood pressure that often leads to right ventricular failure
The diagnosis of primary
has mostly been restricted to the study of patients with
embolism,11 12and its potential role in evaluating patients with
primary pulmonary hypertension is unknown.
The aim of our study was to examine the pulmonary arter-
ies of patients with primary pulmonary hypertension by IVUS
in order to establish their morphological and functional char-
acteristics at baseline and after an acute infusion of epopros-
tenol. We also aimed to correlate clinical and haemodynamic
data with ultrasound measurements and to determine the
relation between pulmonary IVUS findings and mortality at
Twenty two consecutive patients with primary pulmonary
hypertension who underwent cardiac catheterisation at our
institution were included in the study. The diagnosis was
made on the basis of the criteria in the National Institutes of
Abbreviations: EEM, external elastic membrane; IVUS, intravascular
ultrasound; LAs, lumen area in systole; LAd, lumen area in diastole;
NYHA, New York Heart Association; PADP, pulmonary artery diastolic
pressure; PASP, pulmonary artery systolic pressure; P/EE,
pulmonary/elastic strain index
See end of article for
Dr Josep Rodés-Cabau,
Servei de Cardiologia,
Universitari Vall d’Hebron,
P/Vall d’Hebron 119-129,
08035 Barcelona, Spain;
20 November 2002
Duration of symptoms, New York Heart Association
(NYHA) functional class, and the presence of signs of right
ventricular failure were recorded.Clinical follow up was avail-
able in all cases.All patients received anticoagulant treatment,
and all underwent a clinical test with calcium antagonists.
Either intravenous epoprostenol or aerosolised iloprost (both
prostacyclin analogues) was prescribed if clinical worsening
was observed in patients with baseline NYHA functional class
< III, or if no improvement occurred in case of baseline func-
tional class > III. Patients were added to the lung transplant
waiting list if clinical worsening persisted despite epoproste-
nol or iloprost treatment.
The procedures were performed in accordance with the
institutional ethics committee, and all patients gave informed
Cardiac catheterisation: acute epoprostenol test
Right and left heart catheterisation was undertaken with
femoral access. Cardiac output and cardiac index were calcu-
lated by the Fick method, and pulmonary resistance was cal-
culated as mean arterial pulmonary pressure/cardiac output.
Right ventricular stroke work index was calculated as: [mean
pulmonary artery pressure − mean right atrial pressure] ×
stroke volume index × 0.0136 (g.m/m2). After baseline
measurements, an infusion of epoprostenol was started at a
dose of 2 ng/kg/min, and increased progressively until there
was a decrease of more than 30% in pulmonary resistance, or
until side effects occurred. All haemodynamic variables were
measured at the maximum dose of epoprostenol.
Intravascular ultrasound imaging
IVUS examination was done with a 20 MHz, 3.5 French, 64
element circumferential phased array ultrasound catheter
(Endosonics Inc, Rancho Cordova, California, USA), with an
axial resolution of 200 µm. The ultrasound catheter was
advanced into a distal pulmonary artery and images were
recorded on videotape (S-VHS). The intention was to image
two pulmonary lobes per patient. Ultrasound measurements
were recorded at baseline (in all pulmonary arteries studied)
and at the maximum dose of epoprostenol (at the same point
at which the last pulmonary artery was imaged).
Images of the most distal segment studied were analysed
off-line by two observers unaware of clinical and haemody-
namic findings. The following measurements were made:
• vessel diameter
• lumen diameter
• wall (intima + media) thickness (mean, maximum, and
• relative wall thickness: mean wall thickness/lumen diam-
• lumen area in systole (LAs) and in diastole (LAd)
• wall area
• area circumscribed by the external elastic membrane
• percentage wall area: wall area/EEM × 100
• eccentricity index:minimum wall thickness/maximum wall
• pulsatility: LAs − LAd/LAd × 100
• pressure/elastic strain index: (PASP − PADP) × LAd/LAs −
LAd,where PASP = pulmonary artery systolic pressure and
PADP = pulmonary artery diastolic pressure.
The pulmonary artery wall was considered thickened when
maximum wall thickness was > 0.2 mm.7 8Mean wall
thickness was the mean of the four measurements made in
each quadrant of the artery. The wall thickening was consid-
ered eccentric if eccentricity index was < 0.5. The EEM was
represented by the interface between the intima + media and
the more echogenic adventitia. Pulsatility was calculated as
the average value of three consecutive cardiac cycles. The
average value of the measurements made in the two arteries
imaged was used for analysis. For the evaluation of the effects
of epoprostenol on pulmonary vessel pulsatility, only the last
pulmonary artery imaged at baseline was used for comparison
(baseline v maximum dose of epoprostenol).
The lungs of five patients were available for pathological study.
Necropsy was done in two cases and double lung transplanta-
tion was carried out in three, at a mean (SD) of 7 (6) months
(range 2 days to 17 months) after IVUS examination.
Explanted lungs were prepared by the Thurlbeck’s method.14
Five micron thick sections from the samples with medium size
arteries were stained with Verhoef–Van Gieson for elastic tis-
sue. One or two elastic pulmonary arteries were selected from
the lobes previously assessed by IVUS, and the microscopic
image of the vessels was electronically captured,digitised,and
calibrated, performing the same measurements as those
obtained with ultrasound imaging.
Continuous variables were expressed as mean (SD). Student’s
t test was used for comparison of means. The comparison of
more than two means was done by analysis of variance. The
Pearson correlation coefficient was calculated for comparison
of continuous variables. Intraobserver and interobserver vari-
ability of ultrasound measurements was assessed using the
method of Bland and Altman, whereby measurements are
repeatable if 95% of the differences are within 2 SD.15A prob-
ability value of p < 0.05 was considered significant.
Clinical and haemodynamic characteristics
Clinical and baseline haemodynamic variables are given in
table 1. The mean age of the study population was 39 years
(range 16–56 years) and most of the patients were female.
Epoprostenol infusion, at a maximum dose of 10.7 (2.4) ng/
kg/min, significantly increased the cardiac index (from 1.9
(0.66) to 2.7 (0.79) l/min/m2, p < 0.0001), cardiac output
(from 3.3 (1.1) to 4.6 (1.5) l/min, p < 0.0001), stroke volume
(from 39.4 (14.4) to 49.2 (19.6) ml, p < 0.0001), and right
ventricular stroke work index (from 16.1 (5.9) to 19.9
(8.6) g.m/m2,p = 0.006).The epoprostenol infusion decreased
total pulmonary resistance (from 1829 (215) to 1418
pulmonary hypertension. Note the intima + media thickening (soft
echoes) between the arterial lumen and the outer echobright layer
(adventitia). Wall thickening is eccentric, with more prominent
changes between 5 and 12 o’clock. Distance between two white
points is 1 mm. The circular artefact within the lumen is generated by
the ultrasound catheter.
Cross sectional IVUS image from a patient with primary
312Rodés-Cabau, Domingo, Román, et al
(212) dyn.s.cm−5, p < 0.0001), but caused no variation in
mean pulmonary artery pressure (from 63 (20) to 64
(28) mm Hg, p = 0.67).
IVUS examination was undertaken on all patients with no
complications. Thirty six pulmonary lobes were studied, but
the quality of ultrasound images was considered inadequate
for analysis in two patients,who were therefore excluded from
the study. In all, 33 pulmonary lobes (all but three inferior
lobes) were analysed from 20 patients (two pulmonary lobes
were studied in 13, and only one lobe in seven because of low
patient tolerance or difficulty in catheterising a second
pulmonary artery). We were able to analyse the structural
characteristics of the pulmonary wall in 25 pulmonary arter-
ies, but morphological measurements were not made in eight
because the EEM could not be delineated. Pulsatility was cal-
culated in 31 of the 33 arteries studied. All measurements
were reproducible on the basis of the Bland and Altman
The results of IVUS measurements are summarised in table
2. All patients had thickened pulmonary artery walls, leading
to a mean reduction in lumen area of 31.0 (9.3)%. Wall thick-
ening was eccentric in most of the arteries (64%),with a mean
eccentricity index of 0.44 (0.20) (fig 1).
Epoprostenol increased the pulsatility and decreased the
pressure/elastic strain index of pulmonary arteries to some
degree in all but two of the patients (fig 2). Pulsatility
increased by 53% compared with baseline (from 14.6 (5.2)% to
22.4 (7.0)%,p = 0.0001),and the pressure/elastic strain index
decreased by 41% (from 440 (177) to 258 (121) mm Hg,
p = 0.0001).
Relation between clinical status, baseline
haemodynamics, and IVUS findings
There was no correlation between clinical variables (duration
of symptoms, NYHA class, presence of right cardiac failure),
baseline haemodynamics, and IVUS measurements. The
degree of pulsatility and pressure/elastic strain index changes
induced by epoprostenol also did not correlate with the
haemodynamic changes, baseline haemodynamics, or mor-
phological ultrasound measurements (r < 0.5 with p > 0.05
for all correlations).
Clinical follow up was available in all cases. At a mean follow
up of 18 (12) months, nine patients had died, three had
undergone lung transplantation, and eight had remained
clinically stable with no significant change or a mild to mod-
erate improvement in baseline functional class. Five patients
received intravenous epoprostenol and two were treated with
aerosolised iloprost. Death was of cardiac origin in all cases,
and occurred at a mean of 7 (8) months (range 2 days to 19
months) after cardiac catheterisation. Three patients died
suddenly,and the rest had a rapid clinical deterioration,dying
within the two weeks after the worsening of symptoms.
None of the structural variables measured by IVUS had a
significant relation to clinical follow up. However, baseline
pulmonary artery pulsatility was decreased in patients who
died during follow up compared with those who survived
(12.0 (4.4)% v 16.4 (4.4)%, p = 0.03). The pressure/elastic
strain index was also higher in patients who died at follow up
of 20 patients with primary pulmonary hypertension
Clinical and haemodynamic characteristics
Duration of symptoms (months)
NYHA class I–II (n)
NYHA class III–IV
Right ventricular failure (n)
Mean pulmonary artery pressure (mm Hg)
Cardiac output (l/min)
Stroke volume (ml)
Right ventricular stroke work index (g.m/m2)
Total pulmonary resistance (dyn.s.cm−5)
Mean right atrial pressure (mm Hg)
Systemic oxygen saturation (%)
NYHA, New York Heart Association functional class.
Intravascular ultrasound data
Vessel diameter (mm)
Maximum wall thickness (mm)
Mean wall thickness (mm)
Relative wall thickness
Wall area (mm2)
Percentage wall area (%)
Pressure/elastic strain index (mm Hg)
on pulmonary artery pulsatility measured by intravascular ultrasound.
Epoprostenol increased vessel pulsatility from 14.6 (5.2)% to 22.4
(7.0)% (p = 0.0001), and some improvement was detected in 18 of
the 20 patients studied (90%).
Effect of acute administration of intravenous epoprostenol
grouped according to clinical outcome. The median value of
pulmonary pulsatility was 14.0%, range 7.7–26.7% (discontinuous
line). Note that among the patients who survived, 13 of the 17
pulmonary arteries studied had a pulsatility above the median value.
On the other hand, among the nine who died at follow up, only
three of the 14 pulmonary arteries studied had a pulsatility of
Baseline pulsatility in all pulmonary arteries studied,
IVUS in primary pulmonary hypertension313
(369 (67) v 546 (216) mm Hg, p = 0.02). The baseline
pulsatility values of all pulmonary arteries imaged, grouped
according to clinical outcome, are presented in fig 3.
Histological measurements were made in nine elastic pulmo-
nary arteries, with a mean diameter of 2.77 (1.26) mm.
Intimal proliferation and medial hypertrophy was demon-
strated in all arteries (fig 4). Mean wall thickness was 0.41
(0.21) mm, maximum wall thickness was 0.58 (0.28) mm,
relative wall thickness was 0.13 (0.04), wall area was 3.79
(3.27)mm2, percentage wall area was 55 (12)%, and the
proportion of the wall area occupied by the intima was 33
(16)%. Wall thickening was eccentric in 56% of cases, with an
eccentricity index of 0.44 (0.15). Intimal proliferation and
medial hypertrophy were eccentric in six and seven of the nine
arteries studied, respectively. Eccentricity values for intima
and media were 0.36 (0.16) and 0.47 (0.22), respectively.
IVUS adequately depicted the arterial wall changes observed
in the elastic pulmonary vessels of patients diagnosed with
primary pulmonary hypertension. The pulmonary arterial
wall was thickened in all cases to varying degrees, mostly in
eccentric form. Also, ultrasound imaging allowed functional
evaluation of the pulmonary vasculature by measuring
ultrasound morphology, pulsatility, and haemodynamic indi-
ces. An acute vasodilator test with intravenous epoprostenol
improved pulsatility and the pressure/elastic strain index to a
variable extent in 90% of cases, irrespective of the absence of
changes in pulmonary artery pressure. Pulsatility and the
variables that were shown to have prognostic value. Thus pul-
satility and the pressure/elastic strain index were significantly
lower and higher, respectively, in patients who died at the mid
term follow up compared with those who survived.
IVUS evaluation of pulmonary artery morphology
The pulmonary arteries in primary pulmonary hypertension
are characterised by intimal proliferation and fibrosis, medial
hypertrophy, adventitial proliferation, thrombotic lesions, and
obliteration of small arteries.16 17IVUS was able to explore
elastic pulmonary arteries ranging from 2.4–5.3 mm in vessel
diameter, showing wall thickening in all cases. Pulmonary
vessel changes were caused by different degrees of intimal
proliferation and medial hypertrophy, as demonstrated by the
pathology. These changes were eccentric in most cases, owing
to non-uniform medial hypertrophy and intimal proliferation
(fig 4). However, none of the structural wall changes detected
by IVUS correlated with haemodynamic variables.
Previous pulmonary ultrasound studies in patients with
pulmonary hypertension have reported divergent results with
respect to the relation between ultrasound morphological
changes and haemodynamic variables.6 7 9 10The lack of corre-
lation between pulmonary morphology and haemodynamics
could be explained by the fact that the degree of pulmonary
vascular disease is not uniform over the whole lung, and only
one to two pulmonary arteries could be selected for analysis
among all the pulmonary vasculature. Furthermore, the earli-
est alterations observed in primary pulmonary hypertension
occur in the small muscular arteries and arterioles,17and the
structural changes observed in elastic pulmonary arteries are
secondary, only partially reflecting the severity of distal
disease. Finally, pulmonary wall changes are at the same time
the consequence of existing pulmonary hypertension and the
cause of its further evolution,so that these two variables could
have a significant overlap.
The severity of the ultrasound morphological changes of the
pulmonary vessels was of no value in predicting mortality at
follow up in our study. Palevsky and colleagues studied the
lung samples obtained at biopsy in patients with primary pul-
monary hypertension and showed that the only pulmonary
wall change predictive of poor outcome at mid term follow up
was the area occupied by the intima.18We were not able to dif-
ferentiate the intima from the medial hypertrophy owing to
the homogeneous echogenicity across the different layers of
the artery wall, which precluded measurement of the area
occupied by the intima.
Functional evaluation of elastic pulmonary arteries
Previous studies have shown a reduced pulsatility in cases of
secondary pulmonary hypertension compared with controls,
in whom pulmonary pulsatility was about 20%.6 9We have
shown here that pulmonary pulsatility is below 18% in most
cases of primary pulmonary hypertension, and a greater
reduction in baseline pulsatility was associated with a high
mortality at follow up. The pulsatility of an artery depends on
the mechanical forces working on the vessel wall, and the
intrinsic and vasomotor properties of the arterial wall. Vascu-
lar remodelling is a prominent feature of primary pulmonary
hypertension, and several changes of the vessel wall could
explain the reduced pulsatility observed in these cases.Altera-
tions in the intima (proliferation and fibrosis) and media
(increased fibrosis) are described. Also, important changes
occur in the adventitia, where the production of extracellular
matrix (collagen, elastin, fibronectin, and tenascin) is
increased. The absence of a relation between pulsatility and
haemodynamic variables suggests that the changes in pulmo-
nary vessel structure are responsible for the functional altera-
tion shown by ultrasound. The reduced pulsatility in patients
who died at follow up probably reflects more advanced disease
with more severe changes in the vascular structure of the
elastic pulmonary arteries. Furthermore, arterial stiffening
has been shown to increase left ventricular systolic stress,
favouring cardiac dysfunction,19 20and a deleterious effect of a
reduction in pulmonary artery compliance on right ventricu-
lar function has also been suggested.21This may have contrib-
uted to the higher mortality observed in the patients with
decreased pulmonary artery pulsatility.
Prostacyclin is a short acting vasodilator and platelet
inhibitor that is produced by the vascular endothelium. How-
ever, it does not usually have a potent vasodilator effect when
given intravenously as an acute test in patients with primary
obtained from the necropsy specimen of a patient with primary
pulmonary hypertension, showing significant structural changes
caused by proliferation of the intima and medial hypertrophy. Black
and white arrows show the external and internal elastic lamina,
respectively. Note the irregularity of intimal proliferation and medial
hypertrophy, leading to eccentric wall thickening (×7.8, Verhoef Van
Histological section of an elastic pulmonary artery
314Rodés-Cabau, Domingo, Román, et al
pulmonary hypertension, and there is often minimal or even
absent lowering of mean pulmonary artery pressure.22
However, long term treatment with epoprostenol (a prostacy-
clin analogue) produces sustained haemodynamic benefit and
improved survival, even in patients with no response to an
acute infusion.3 18 22–24It has been suggested that an effect of
epoprostenol on pulmonary vascular remodelling is responsi-
ble for these beneficial long term effects.25–27Our study has
shown that intravenous epoprostenol could significantly
improve pulmonary artery pulsatility irrespective of haemody-
cardiac flow indices and global pulmonary vascular compli-
ance,the absence of a correlation between increases in cardiac
output/stroke volume and changes in pulmonary artery
pulsatility induced by epoprostenol was unexpected.Although
cardiac function and pulmonary artery pulsatility improved in
most patients, there was no correlation between the changes
in these variables. One explanation for this could be that pul-
monary pulsatility was measured as lumen area change in a
single elastic pulmonary artery and not as overall distensibil-
ity of the pulmonary vascular bed, a problem compounded by
the heterogeneity of pulmonary blood flow.28Also,the absence
of a relation between pulmonary flow and pulsatility changes
induced by epoprostenol might suggest a direct positive effect
of this type of drug on the vasomotor properties of the artery
wall, which have been shown to contribute substantially to
vessel elasticity.29However, only by measuring the pulmonary
flow changes at the level of the artery imaged could we have
determined whether the improvement in pulmonary pulsatil-
increase in blood flow, or both.
As indicated in previous studies, the recognition of the elastic
external membrane is the most important limiting factor for
ultrasound pulmonary morphology evaluation. In our study,
IVUS did not provide adequate images for morphological
evaluation in up to 25% of the pulmonary arteries evaluated,
and two patients had to be excluded because of the poor qual-
ity of the images. However, in most cases ultrasound images
were adequate for analysis, and IVUS measurements were
reproducible A relation between ultrasound and pathological
findings could not be established because the mean delay
between the ultrasound exploration and the histopathological
studies was too long, and even if the pathologist had studied
elastic pulmonary arteries from the same pulmonary lobe as
had previously been imaged by IVUS, it would not have been
possible to evaluate the same elastic pulmonary artery.
A control group would have provided more consistency in
the study results, although previous studies with control sub-
jects have already defined the ultrasound characteristics of
pulmonary arteries with no pathological features.6 7Also, the
inclusion of a control group would have incurred ethical
Finally, the small sample size inevitably lessens the
potential of the results obtained and precludes the perform-
ance of multivariate analysis to establish the prognostic value
of the ultrasound findings more accurately.
IVUS provides combined morphological and functional evalu-
ation of the elastic pulmonary vessels of patients with primary
pulmonary hypertension and allows direct assessment of the
acute changes induced in the pulmonary vessel wall dynamics
by epoprostenol. The exploration is safe, and can be
undertaken at the same time as cardiac catheterisation.
Finally, there is an association between impaired pulmonary
artery functional state as determined by IVUS and mortality
at follow up. However, larger series are needed to determine
the exact prognostic value of this technique in the setting of
primary pulmonary hypertension.
in part by a grant from the Societat Catalana de Cardiologia.
J Rodés-Cabau, E Domingo, F Padilla, I Anívarro, J Angel,
J Soler-Soler, Department of Cardiology, Hospital Universitari Vall
d’Hebron, Barcelona, Spain
A Román, B Lara, Department of Pneumology, Hospital Universitari Vall
J Majó, Department of Pathology, Hospital Universitari Vall d’Hebron
J C Tardif, Department of Medicine, Montreal Heart Institute, Montreal,
1 Rubin LJ. Primary pulmonary hypertension. N Engl J Med
2 D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary
pulmonary hypertension: results from a national prospective registry. Ann
Intern Med 1991;115:343–9.
3 Shapiro S, Oudiz R, Cao T, et al. Primary pulmonary hypertension:
improved long-term effects and survival with continuous intravenous
epoprostenol infusion. J Am Coll Cardiol 1997;30:343–9.
4 Pandian NG, Weintraub A, Kreis A, et al. Intracardiac, intravascular,
two-dimensional high frequency ultrasound imaging of pulmonary artery
and its branches in humans and animals. Circulation 1990;81:2007–12.
5 Ishii M, Kato H, Kawano T, et al. Evaluation of pulmonary artery
histopathologic findings in congenital heart disease: an in vitro study
using intravascular ultrasound imaging. J Am Coll Cardiol
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IMAGES IN CARDIOLOGY.............................................................................
Epidural haematoma presenting as polymorphic ventricular tachycardia
mechanical valve replacement for rheumatic mitral valve dis-
ease and atrioventricular node ablation and pacemaker
implantation for atrial fibrillation. Her 12 lead ECG demon-
strated a ventricular paced rhythm but profound prolongation
of QT interval (QTc = 694 ms). An ECG performed two years
previously had demonstrated her QT interval to be within
normal limits. Her arrhythmias resolved with reprogramming
of her pacemaker to a faster ventricular rate.
Soon after admission she became paraplegic with a sensory
level to T10. Subsequent myelography and computed tomo-
graphic imaging demonstrated frank blood in the cerebrospinal
fluid and an extradural haematoma at the level of T4 with com-
plete blockage of contrast flow. This was managed conserva-
tively with reversal of her anticoagulation. She made a limited
neurological recovery.Her ECG returned to normal.
Interpretation of repolarisation changes on the surface ECG in
a paced rhythm is difficult. However, in this case normal
repolarisation had been demonstrated before and after the
with polymorphic ventricular tachycardia have previously been
reported in patients with subarachnoid haemorrhage.It is feasi-
the subarachnoid space precipitating her arrhythmias.
60 year woman presented with recurrent syncope and
frequent episodes of self terminating polymorphic ven-
tricular tachycardia. She had a previous history of
T R Webb
J M Morgan
P R Roberts
severe aortic regurgitation; abscess formation and valvar ring
destruction were found during surgery,and tissue culture yielded
meningococcus. The patient remained asymptomatic until 1995,
when aortic regurgitation recurred. Surgical repair of the
prosthetic ring was successfully undertaken.
Transoesophageal echocardiography was undertaken. As
can be seen below, a large aortic abscess is visible in the aortic
67 year old obese women with hypertension and diabetes
was admitted to our hospital because of fever and anaemia.
In 1987 a Bjork-Sorin 21 prothesis was implanted for
ring (Abs), which extends to the interatrial septum and left
atrium (Ai); vegetation on the aortic prothesis and prosthetic
aortic regurgitation are evident.
Staphylococcus epidermidis was isolated in blood cultures. Sur-
gery was performed,confirming the findings.The patient died
during the procedure.
M L R Suárez
L R Redondo
T R Raviña
316 Rodés-Cabau, Domingo, Román, et al