European Journal of Echocardiography 2008 9(2):338-341; doi:10.1093/ejechocard/jen017
Published on behalf of the European Society of Cardiography. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org
Myocardial contrast echocardiography in biopsy-proven primary cardiac amyloidosis
Sahar S. Abdelmoneim,
Mathieu Bernier,
Diego Bellavia,
Imran S. Syed,
Sunil V. Mankad,
Krishnaswamy Chandrasekaran,
Patricia A. Pellikka and
Sharon L. Mulvagh*
Mayo Cardiovascular Ultrasound Imaging and Hemodynamic Laboratory, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Received 15 October 2007; accepted after revision 2 January 2008.
* Corresponding author. Tel: +1 507 284 8612. E-mail address: smulvagh{at}mayo.edu
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Abstract
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Cardiac vasculature is affected in 88–90% of patients
with primary cardiac amyloidosis (CA). Myocardial contrast echocardiography
(MCE) relies on the ultrasound detection of microbubble contrast
agents that are solely confined to the intravascular space,
and are therefore useful in the evaluation of flow in the microvasculature.
This is the first case report describing the use of MCE during
vasodilator stress to evaluate coronary flow reserve in a patient
with biopsy-proven primary CA and angiographically normal coronaries.
Qualitative MCE demonstrated delayed replenishment of microbubbles
during peak stress; quantitative analysis was consistent with
a reduction in total myocardial blood flow and reserve values.
Comparative imaging modalities including strain and strain rate
imaging, magnetic resonance imaging, and myocardial scintigraphy
were suggestive to the diagnosis of CA. In conclusion, MCE is
a method for recognition of microvascular dysfunction, and might
be considered as a useful tool to augment echocardiographic
assessment in the early diagnosis of CA.
Keywords: Amyloidosis; Contrast; Echocardiography
A 62-year-old man presented with weight loss and worsening fatigue.
Past medical history was unremarkable. Physical examination
was normal. A 12-lead electrocardiogram (ECG) revealed normal
sinus rhythm with low anteroseptal forces. Transthoracic echocardiography
demonstrated normal wall motion of the left ventricle (LV) and
right ventricle (RV) with mildly increased LV wall thicknesses
(LV septum and posterior wall thickness of 14 mm) (
Figure 1,
see Supplementary material online, Movies 1 and 2). Estimated
LV ejection fraction (EF) was 61% with LV diastolic dysfunction
(pseudo normal transmitral pattern; Grade 2 of 4). Global Doppler
myocardial imaging (DMI) studies were done, which demonstrated
marked impairment particularly in the lateral and anteroseptal
walls, with a mean tissue velocity of 2.9 ± 3.5 cm/s,
mean strain of –9.7 ± 7.8% and strain rate of –0.8
± 0.6 (1/s). These findings were consistent with the
diagnosis of cardiac amyloidosis (CA). Serum and urine samples
showed elevated lambda light-chain proteins. Bone marrow biopsy
and subcutaneous fat aspirate showed amyloid deposits, confirmed
by Congo red stain. Cardiac magnetic resonant imaging (MRI)
was performed to evaluate CA further. Steady-state free precession
(SSFP) cine-sequences demonstrated diffuse LV and RV thickening
(
Figure 2A and
B, see Supplementary material online, Movie
3). First-pass MRI (bolus of 0.1 mmol/kg gadolinium-DTPA) revealed
normal perfusion at rest. Delayed enhancement images (bolus
of 0.2 mmol/kg gadolinium-DTPA) demonstrated poor signal to
noise, an unusual dark appearance of the blood pool, and suboptimally
nulled myocardium with mild diffuse heterogeneous but predominantly
subendocardial hyperenhancement (
Figure 2C). These MRI
findings are consistent with CA. On coronary angiography, no
epicardial atherosclerosis was noted and dominant vessel was
the right coronary artery. RV endomyocardial biopsy confirmed
amyloid depositions that were only positive for lambda immunoglobulin
light chains. These depositions included severe interstitial
and pericellular involvement with non-obstructive vascular deposits
and focal endocardial deposits. All these findings confirmed
the diagnosis of AL-type amyloidosis. Real-time myocardial contrast
echocardiography (MCE) was used during an established research
protocol with adenosine stress (Adenoscan; Astellas, USA: dose
of 140 µg/kg/min over 6 min). After obtaining informed
consent, MCE was performed using Definity® (BMS, USA). Microbubble
destruction replenishment imaging sequences were performed using
SONOS 7500, power modulation (Philips Medical System, Best,
The Netherlands). Qualitative MCE revealed normal homogenous
contrast perfusion at rest (
Figure 3, see Supplementary
material online, Movie 4). Despite normal wall motion at peak
adenosine stress, a moderate decrease in myocardial perfusion
of the apical regions in apical four chamber, and apical two
chamber views by the second beat post microbubble destruction
(flash) was noted, which eventually perfused by the 8th beat
post destruction (delayed perfusion) (
Figure 4, see Supplementary
material online, Movie 5). Quantitatively, replenishment of
contrast characterized by time intensity curves fitted to the
monoexponential function
y =
A(1–e
–βt) was
derived, where
β is the slope of the replenishment curve,
reflecting microbubble velocity, and the plateau (
A) of microbubble
videointensity reflects microvascular cross section area (
Figure 5).
To adjust for inhomogeneous contrast enhancement of the myocardium,
segmental videointensity was corrected for the blood pool cavity
videointensity (
Amyocardium/
Acavity) for each segment. The MCE-derived
value of absolute myocardial blood flow (MBF =
A x β) and
their reserve values (stress/rest) were calculated. The median
MBF derived from 16 LV segments was 0.515 [interquartile range
(IRQ); 0.303, 0.886] at rest, and was 0.412 (IRQ; 0.246, 1.137)
at peak stress. Coronary flow reserve value was 0.780 (IRQ;
0.326, 1.935). Two cycles of Melphalan/dexamethasone chemotherapy
were initiated while preparing for stem cell collection and
transplant. The patient tolerated the chemotherapy well with
partial response of drop of lambda free light chain from 11.9
to 4.7 mg/dL and 24 h urine protein drop from 6 to 3 gm.
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Figure 1 Transthoracic echocardiogram (Harmonic imaging); (A) four-chamber view and (B) two-chamber view showing increased thickening of the left and right ventricular myocardium. LV, left ventricle; RV, right ventricle; LA, left atrium; RA, right atrium.
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Figure 2 Cardiac magnetic resonant imaging; four-chamber steady-state free precession images in end-diastole (A) and end-systole (B) demonstrates diffuse right and left ventricular thickening. The tricuspid valve is also thickened (best appreciated in the end-systolic frame). Image artifact partially obscures the mitral valve. (C) Mid-ventricular short-axis delayed enhancement acquisition demonstrates suboptimal myocardial nulling, an unusually dark appearance of the blood pool, and mild diffuse heterogenous but predominantly subendocardial hyper enhancement (arrow).
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Figure 3 Baseline (rest) myocardial contrast echocardiography (subsequent end-systolic frames) in apical two-chamber view showing homogenous contrast replenishment of the myocardium by the 5th beat post destruction.
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Figure 4 Adenosine stress myocardial contrast echocardiography (subsequent end-systolic frames) in apical two-chamber view showing a perfusion defect at the apex (arrow) at the 2nd beat post destruction; this replenishes gradually by the 8th beat (delayed perfusion).
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Figure 5 Adenosine stress myocardial contrast echocardiography (subsequent end-systolic frames) with apical region of interest for quantification (apical two-chamber view) and replenishment curve with slope (β) and plateau value (A) fitted to a monoexponential function. (A) Baseline; (B) stress where the slope and plateau are decreased in comparison with the curve at baseline.
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This is the first case report describing the use of MCE during
vasodilator stress in a patient with biopsy-proven primary CA
and angiographically normal coronaries. Clinical evidence of
cardiac involvement occurs in up to 50% of patients with AL
amyloidosis. Cardiac vasculature is affected in 88–90%
of patients with primary CA.
1,2 Intramural amyloid deposition
within the coronary arteries leads to vessel wall thickening
and luminal narrowing.
3 Previous studies reported impairment
of endothelial-dependent (acetylcholine) and endothelial-independent
(adenosine) coronary flow reserve in patients with amyloidosis
who presented with chest pain and normal angiogram with no clinical
or biochemical evidence of amyloidosis at the time of presentation.
4 In conclusion, MCE is a method for recognition of microvascular
dysfunction, and might be considered as a useful tool to augment
echocardiographic assessment in the early diagnosis of CA.
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Supplementary material
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Supplementary material associated with this article can be found
in the online version.
Conflict of interest: none declared.
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References
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- Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart: a comprehensive review. Arch Intern Med (2006) 166:1805–13.[Abstract/Free Full Text]
- Kwong RY, Falk RH. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation (2005) 111:122–4.[Free Full Text]
- Neben-Wittich MA, Wittich CM, Mueller PS, Larson DR, Gertz MA, Edwards WD. Obstructive intramural coronary amyloidosis and myocardial ischemia are common in primary amyloidosis. Am J Med (2005) 118:1287.[Medline]
- Al Suwaidi J, Velianou JL, Gertz MA, Cannon RO III, Higano ST, Holmes DR Jr, et al. Systemic amyloidosis presenting with angina pectoris. Ann Intern Med (1999) 131:838–41.[Abstract/Free Full Text]
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