pre and post transplant echo , contrast echo

PRE AND POST OPERATIVE ECHO IN HEART TRANSPLANT
CONTRAST FOR CHAMBER OPACIFICATION
Why Don’t We Give It To Everyone?
Don’t Burst My Bubbles
DR.G.ABISHEK

OUTLINE
• INTRODUCTION
• DONOR SELECTION
• PRE TRANSPLANT
• POST TRANSPLANT
• ALLOGRAFT VASCULOPATHY
• SERIAL FOLLOW UP
• BASICS OF CONTRAST AGENTS
• CLINICAL APPLICATIONS
• SAFETY ISSUES
• CONCLUSION

INTRODUCTION
• Cardiac transplantation remains the treatment of choice for appropriate candidates with end-stage
heart failure.
• More than 3000 cardiac transplants are performed worldwide annually.
• mortality rate is greatest in the first 6 months after transplantation; the 1-year survival rate after
cardiac transplantation is about 85%, with a 3% to 4% linear decrease annually thereafter and a
median survival rate of 10.4
• first year after transplantation-----Graft failure and infections
• 5 years------cardiac allograft vasculopathy (transplant coronary disease), late graft failure (likely a
result of allograft vasculopathy), and malignancy disease are more common causes of death.

EVALUATION BEFORE CARDIAC
TRANSPLANTATION
• In the context of evaluation before possible cardiac transplantation, right heart function and presence of
pulmonary hypertension are of particular interest.
• Preoperative pulmonary hypertension, particularly if not medically reversible with vasodilators or if
reversible at the expense of systemic hypotension, is associated with very high risk of short-term
mortality, frequently as a result of right heart failure.
• Although direct measurement of central hemodynamics with a pulmonary artery catheter is currently
the gold standard, echocardiography has the advantage of being noninvasive and more widely
available.

PVR =[(PEP)/AcT/TT]
PEP is preejection period
AcT is acceleration time
TT is total systolic time

EVALUATION OF THE DONOR HEART
• For regional and global wall motion abnormalities, and valvular or congenital abnormalities.
• Although regional or global wall motion abnormalities may be present on initial assessment, in
some cases, contractile function can be improved with medical therapy, particularly if the
dysfunction is related to brain death or is catecholamine induced.
• Serial echocardiograms can often confirm improvement in contractile function in the setting of
hemodynamic and metabolic correction.
• Lower the initial ejection fraction, the less likely the heart is able to be optimized for use for
transplantation because this likely reflects intrinsic and irreversible causes for contractile
dysfunction.

INTRAOPERATIVE TEE EVALUATION OF HEART TRANSPLANTATION
• Structural Problems
Inferior vena cava (IVC) stenosis
Pulmonary artery (PA) stenosis
Intracardiac air
• Functional Problems
Tricuspid regurgitation (TR)
Mitral regurgitation (MR)
Pulmonary vein obstruction
Right ventricular dysfunction
Left ventricular dysfunction
Hypovolemia
Volume overload

PHYSIOLOGY OF THE CARDIAC ALLOGRAFT
• Hemodynamics immediately after cardiac transplantation are characterized by elevated filling
pressures associated with impaired relaxation.
• Restrictive physiology early after transplantation may be the result of a combination of ischemic
myocardial injury, recipient pulmonary hypertension, and volume overload.
• Persistent restrictive physiology may be attributed to donor-recipient size mismatch, ischemic
fibrosis, increased afterload from systemic hypertension, or rejection.
• Denervated, the cardiac allograft has an altered response to exercise, characterized by a slower
early rise in heart rate and an overall blunted chronotropic response, with increases in cardiac
output primarily the result of increases in stroke volume rather than heart rate.
• Sympathetic reinnervation occurs over time and is associated with improved exercise capacity,
including heart rate and ventricular contractile response to exercise.
• Exercise capacity improves in the initial few years after transplantation but may never reach
normal nontransplant levels.

Early postoperative complications
•Early postoperative problems that may be diagnosed and evaluated with echocardiography include
pericardial effusion or tamponade, right ventricular dysfunction, tricuspid valve regurgitation, and
acute allograft failure.
Pericardial effusion
•Moderate to large-sized pericardial effusions in the postoperative period (9% to 35%).
•These effusions do not appear to negatively impact survival, and there does not appear to be a
correlation with occurrence of rejection.
•Pericardial effusion that occurs more than 1 month after transplantation associated with less
favorable implications.
•Association between late-onset persistent or increasing pericardial effusion with occurrence and
severity of rejection.

Ventricular Systolic Function
• Early after transplantation, LV mass and end-diastolic volume increase; these changes may or may
not persist for years, without adverse consequences to ejection fraction, although subtle dec-
rements in systolic contractility may manifest early.
• In the absence of complications that cause graft dysfunction, allograft ventricular systolic function
generally remains normal as many as 10 to 15 years after transplant.
• LV hypertrophy is a common finding, as is postoperative septal motion.
• Systolic ventricular function remains largely normal

Diastolic Function
• Diastolic function is abnormal early after transplantation, the effects of which are frequently
compounded by postoperative volume overload.
• A restrictive filling pattern may persist to some degree chronically in some patients or may
reemerge during episodes of acute rejection.
• Early after transplantation, a restrictive filling pattern is present, characterized by shorter
isovolumic relaxation time and E wave deceleration time and an increased E/A ratio , with gradual
evolution to a nonrestrictive pattern by 6 weeks after transplantation.
• Clinical factors, such as preoperative pulmonary systolic pressures or pulmonary vascular
resistance, duration of cardiopulmonary bypass, total ischemia time, or age of donor heart, did not
significantly correlate with parameters of restrictive filling early after transplantation.

Pre transplant Post transplant

• The incidence of diastolic dysfunction decreases over time, but diastolic abnormalities persist
beyond the early postoperative period in a small proportion of patients.
• Right ventricular diastolic dysfunction (elevated right atrial pressure to stroke volume ratio) was
associated with increased mortality.
• In general, transplant recipients with constrictive-restrictive hemodynamics had higher right-sided
and left-sided filling pressures, shorter LV isovolumic relaxation times and E wave deceleration
times, and higher mitral and tricuspid E/A ratios.
• Persistence of restrictive filling pattern up to 6 months after cardiac transplantation may be
associated with reduced long-term survival.
• The etiology of persistent diastolic dysfunction after transplantation is not fully defined but likely
includes cumulative immune-mediated injury, fibrosis related to immune or nonimmune damage,
and allograft vasculopathy.

RIGHT VENTRICULAR STRUCTURE AND FUNCTION
• A significant proportion of patients with severe heart failure have pulmonary hypertension as a
result of longstanding elevated left-sided filling pressures.
• Pulmonary hypertension frequently improves to normal or near-normal levels in the weeks to
months after cardiac transplantation.
• The evolution of right sided structure and function after transplantation parallels the resolution of
pulmonary hypertension and volume overload , although some right ventricular enlargement may
persist long term.

TRICUSPID REGURGITATION
• Tricuspid regurgitation occurs early and late after cardiac transplantation.
• Early tricuspid regurgitation is more related to preoperative and postoperative pulmonary
hypertension and right ventricular failure,
• Valve injury from endomyocardial biopsies is often responsible for late tricuspid regurgitation
• Severity of tricuspid regurgitation on intraoperative transesophageal echocardiogram may be a
marker for right ventricular dysfunction and appears to correlate with poor late survival..
• These patients are at increased risk for heart failure and may need tricuspid valve replacement

Echocardiographic Abnormalities Of The
Cardiac Allograft During Rejection

• Changes in systolic and diastolic function.
• Increases in LV wall thickness or mass.
• Gold standard for diagnosis of rejection is with
endomyocardial biopsy

Structure And Function Of The Cardiac Allograft During
Acute Rejection
• Acute cardiac allograft rejection is usually characterized by lymphocytic infiltration with or
without myocyte necrosis, termed “cellular rejection.”
• Endothelial cell activation and complement deposition that primarily involves the allograft
vasculature termed “antibody-mediated rejection” (also called vascular or humoral rejection)
• Classification
• grades 0
• 1R, mild rejection
• 2R, moderate rejection
• 3R, severe rejection

CHANGES IN SYSTOLIC AND DIASTOLIC FUNCTION
• New-onset systolic dysfunction in the setting of acute rejection is generally a late finding and
indicates higher grade rejection, which is associated with hemodynamic compromise and clinical
symptoms and with poorer prognosis.
• The vast majority of rejection episodes are not associated with systolic impairment, and significant
changes in echocardiographic systolic function parameters are generally lacking.
• Abnormalities of diastolic filling are the earliest alterations to manifest in acute rejection.
• Rejection of increasing severity has been associated with a progressive shortening of isovolumic
relaxation time and pressure half-time and with an increase in peak early mitral flow velocity,
• Measures of diastolic dysfunction generally return to baseline values after treatment of acute
rejection.

TISSUE- DOPPLER IMAGING
• Late diastolic mitral annular velocity (a′) and mitral annular systolic velocity (s′) appear to be
sensitive markers of acute severe rejection, they are not particularly specific.
• The combined peak systolic and peak diastolic velocity (peak-to-peak amplitude) of the tissue-
doppler mitral annular waveforms was significantly lower in patients experiencing any rejection
and may be helpful in excluding presence of significant rejection.

CHANGES IN LEFT VENTRICULAR MASS OR WALL THICKNESS
• Although older reports have suggested LV mass increases in the setting of acute cellular rejection, this has not
been a consistent finding and change in LV wall thickness alone has not proven to be a sensitive enough
marker for diagnosis of cellular rejection.
• Increased LV mass in the setting of rejection may be the result of increased interstitial edema or vascular
leakage of fibrin due to “antibody-mediated rejection” (also called vascular or humoral rejection)
• In a series of 41 cardiac transplant patients, LV mass increased from a baseline of 109 ± 17 g to 151 ± 17 g
during vascular rejection, although it did not signicantly change during cellular rejection.
• Concurrently, LV wall thickness increased by nearly 20% during vascular rejection (1.3 ± 0.1 cm at baseline
versus 1.6 ± 0.1 cm).

Echocardiographic Guidance For Endomyocardial Biopsy
• Endomyocardial biopsy remains the gold standard for diagnosing allograft rejection and following response to
immunosuppressive treatment for rejection.
• Echocardiography has been successfully used to guide endomyocardial biopsies with the benefits of lack of
radiation exposure, portability, and provision of information on cardiac structure and function.
• Complication rates with echocardiography for biopsies are extremely low and comparable with those for
fluoroscopic guided biopsies
• One disadvantage is that initial insertion and advancement of the bioptome from the superior vena cava until
entry into the right atrium is not directly visualized with echocardiography.
• The development of severe tricuspid regurgitation in the cardiac allograft is correlated with the total number
of biopsies performed.

Post transplant Monitoring
Routine Follow-up
Echocardiography is primarily used for
1.routine monitoring of cardiac allograft structure and function,
2.valvular abnormalities such as tricuspid regurgitation;
3.as part of stress imaging for cardiac allograft vasculopathy surveillance
4.as an adjunct to endomyocardial biopsy in the diagnosis of acute rejection.
•For patients with suspected acute rejection, an echocardiogram should be obtained with particular
attention paid to identification of changes in measures of systolic and diastolic function.
•Comparison with prior echocardiograms obtained when no rejection was present may be helpful.

DIAGNOSIS OF CARDIAC ALLOGRAFT VASCULOPATHY
• Primary factors limiting the long-term functioning and life span of the allograft.
• Allograft vasculopathy is an accelerated form of intimal hyperplasia that likely results from both
immune and nonimmune mechanisms.
• A classic finding is diffuse “pruning” of the smaller distal coronary vasculature, although discrete
stenoses characteristic of native coronary disease may develop as well.
• In addition to transplant specific immunologic risk factors, typical risk factors for native coronary
disease, such as dyslipidemia and hypertension, also impact the development of cardiac allograft
vasculopathy.
• As a result of cardiac denervation, clinical symptoms from cardiac allograft vasculopathy are
frequently late and atypical, if at all

Coronary Angiography with Intravascular Ultrasound
• Coronary angiography is relatively insensitive in detection of early transplant vasculopathy; up to three
quarters of patients with intimal thickening with intravascular ultrasound (IVUS) have normal coronary
angiograms.
• Coronary angiography, which defines the luminal silhouette of the coronary artery, is not able to detect the
often diffuse and concentric intimal hyperplasia that characterizes allograft vasculopathy.
• Because IVUS images vascular wall morphology, it has emerged as the gold standard for detection of
transplant vasculopathy, particularly in its early stages.
• Extent of vasculopathy can be quantified according to intimal thickness and circumferential extent and also
by change in measures of plaque burden over time.

Dobutamine stress echocardiography
• Highly sensitive and specific in detection of cardiac allograft vasculopathy.
• Positive dobutamine stress echocardiography is associated with increased risk of cardiac events, including
myocardial infarction and heart failure, and risk for death.
• Dobutamine stress echocardiography appears to agree better with IVUS–diagnosed disease
• Performs better than nuclear medicine myocardial perfusion scans
• Sensitivity of stress echocardiography with exercise is somewhat limited by the blunted heart rate response to
exercise that occurs from cardiac denervation; sensitivity 15% to 20%.
• Worsening on serial dobutamine stress echocardiogram studies is variably accurate in diagnosis of
angiographic/IVUS cardiac allograft vasculopathy,
• The addition of quantitative M-mode analysis or strain rate imaging to standard dobutamine stress
echocardiography may also improve its diagnostic accuracy.

CORONARY FLOW VELOCITY RESERVE
MEASUREMENT

CONTRAST FOR CHAMBER OPACIFICATION

Ideal contrast agent
1. Non-toxic
2. Intravenously injectable
3. Has to behave similarly to blood
4. Crosses pulmonary filter
5. Resistant to intravascular and intra-cardiac pressures
6. Stable throughout during the exam
7. Improve the Doppler signal-to-noise ratio

MICROBUBBLE FORMULATIONS
Name Size (µm) Shell composition Gas content indication
AI-700 2.9 SYNTHETIC POLYMER PERFLUORO CARBON Myocardial perfusion
CARDIOspere 4.0 POLYMER BILAYER NITROGEN Myocardial perfusion
DEFINITY
(USA)
1.1-3.3 Lipid encapsulated PERFLUOROPROPANE LV opacification
OPTISON7
(USA)
2.0-4.5 DENATURED ALBUMIN PERFLUOROPROPANE LV opacification
SONOVUE
(EUROPE, ASIA)
2.5 PHOSPHOLIPIDS SULPHUR
HEXAFLUORIDE
Myocardial perfusion,
LV opacification

LOW–MECHANICAL-INDEX IMAGING SCHEMES

Low Mechanical Index High Mechanical Index

Assessment Of Cardiac Structure And Function
• The use of echocardiographic contrast agents for LVO is particularly helpful when
standard resting echocardiographic imaging is unyielding, which often occurs in
patients who are obese, have lung disease, are critically ill, or are receiving
ventilator care.

Quantification of LV volumes and LVEF
• The accurate determination of LVEF is critically important for managing patients with
cardiovascular disease, and it has prognostic value for predicting adverse outcomes in patients
with congestive heart failure, after myocardial infarction, and after revascularization.
• Contrast-enhanced echocardiography defines the endocardial border better than unenhanced
echocardiography.
• Compared with unenhanced echocardiography shows better agreement and reduction in
intraobserver and interobserver variabilities in measured lv volumes and lvef.
• The underestimation of cardiac volumes by echocardiography is nearly resolved when contrast
agents are used.

Cardiac anatomy
Echocardiographic contrast agents also have been of value in the structural assessment of the left and
right ventricles, the atria, and the great vessels.
1.LV apical abnormalities
2.LV apical hypertrophy
3.LV noncompaction
4.LV apicalthrombus
5.LV apical aneurysm
6.Complications of myocardial infarction:-LV pseudoaneurysm, free- wall rupture, and post–
myocardial infarction ventricular septal defects

LV Apical Hypertrophic Cardiomyopathy

Perfusion Imaging With Real-time PerfusionEchocardiography

Intracardiac masses.
• Most malignancies have abnormal neovascularization that supplies rapidly growing tumor cells,
often in the form of highly concentrated, dilated vessels.
• Contrast hyperenhancement of the tumor (compared with the surrounding myocardium) suggests a
highly vascular or malignant tumor.
• Conversely, stromal tumors (such as myxomas) have a poor blood supply and appear
hypoenhanced.
• Thrombi are generally avascular and show no enhancement.

Intracardiac Mass vs. Thrombus
Kirkpatrick JN, et al. JACC 2004.

Extracardiac anatomy(Vascular imaging)
Aortic dissection:
•In patients with aortic dissection or great-vessel dissection, or both, contrast enhancement helps
delineate the true and false lumens.
•entry or exit point of the dissection may be identified, and extension of the dissection plane into
major aortic branches (brachiocephalic, subclavian, celiac, or renal) may also be visualized.
•Femoral arterial pseudoaneurysms:

Doppler enhancement
• Contrast enhancement of the doppler signal has been shown to be of value when the signal is weak
or technically suboptimal.
• Peak velocity measurement in patients with aortic stenosis may be enhanced with
echocardiographic contrast agents.
• Transmitral, pulmonary venous flow velocities regurgitant velocities (for assessing pulmonary
artery systolic pressure) can be enhanced by either agitated bacteriostatic saline contrast or
commercially available echocardiographic contrast agents.

Contrast Enhancement Of Aortic Stenosis Signal

Shunt Detection
• Right-to-left shunts (agitated saline - agent of choice)
• Atrial septal defects of all types
• Patent foramen ovale
• Pulmonary arteriovenous malformations
• Larger ventricular septal defects during diastole
• Left SVC
• Left-to-right shunt
• Negative contrast effect

Right-to-left shunt Negative contrast effect

Echocardiography in the Emergency Department
• Contrast echocardiography can also assess myocardial perfusion, provides incremental diagnostic
and prognostic utility.
• The combination of abnormal myocardial function and perfusion had an odds ratio of for the
development of an early event.
• Echocardiography in the emergency department can play a substantial role in the triage of patients
with chest pain through the accurate diagnosis or exclusion of acute ischemic syndromes and the
prediction of early and late cardiac events.

Contrast Agent Use In The ICU
• In ICU hyperinflated lungs due to mechanical ventilation, lung disease, subcutaneous emphysema,
surgical incisions, chest tubes and bandages, crowded quarters, and poor lighting, endocardial
resolution is frequently suboptimal
• The use of contrast echocardiography overcomes several of the disadvantages associated with standard
echocardiographic imaging in the ICU and can be beneficial for assessment of global and regional
ventricular function.
• Several studies have demonstrated their safety and allowed a more accurate estimation of wall motion
and global function, with results similar to those achieved with TEE.
• contrast enhancement can be helpful in characterizing or confirming pericardial effusion with
associated cardiac tamponade and aortic dissection.

Contrast Agent Use in Cardiac Interventional Therapy
• Direct intracoronary injection of contrast agents into suspected culprit septal perforator arteries
during transthoracic echocardiographic monitoring has been used to identify the septal artery in
patients with hypertrophic cardiomyopathy who are undergoing alcohol ablation for chemical
myectomy.
• According to FDA sthe intracoronary use of contrast agents is contraindicated.

Transcatheter alcohol septal ablation

Use of Contrast Agents in Pediatric Echocardiography
• Ultrasound contrast is not approved by the FDA for use in pediatric patients because the safety and efficacy of
contrast agents have not been established definitively in children.
• Stress echocardiography role in kawasaki disease , arterial switch operation.
• Functional evaluation of the right ventricle in patients after repair tetralogy of fallot and senning and mustard
procedures.
• With significant intracardiac shunts, microspheres may bypass filtering by the pulmonary capillary bed and
directly enter the arterial circulation, potentially resulting in microvascular obstruction.
• Contrast use in pediatric patients has not been associated with adverse effects when used in patients without
significant intracardiac shunts or severely increased pulmonary vascular resistance.

Contrast Enhancement in Stress Echocardiography

• Detection of CAD with stress echocardiography is based on the observation of contractile
dysfunction in any myocardial segment at rest or with stress, complete visualization of all LV
endocardial borders is necessary to document or exclude abnormalities of regional myocardial wall
thickening confidently.
• The documented benefits of using contrast enhancement for LVO with resting echocardiography
(ie, improved EBD, assessment of ventricular volumes and ejection fractions, recognition of wall-
motion abnormalities, and enhanced reproducibility) clearly translate into benefits for stress
echocardiography.
• Contrast echocardiography can convert a technically difficult, nondiagnostic stress
echocardiogram into an accurate diagnostic study and avoid either an unachievable or a missed
diagnosis.
• This obviates the need for alternative testing and improves efficiency, resulting in cost savings.

Exercise stress echocardiogram

SAFETY OF ECHOCARDIOGRAPHIC CONTRAST
AGENTS

FDA “Black Box” Warning
• Issued on October 10, 2007
• Post-marketing reports of 11 deaths 1-12 hours following administration of perflutren-based
contrast agents
• 10 patient deaths following Definity injection and 1 death following Optison injection
• 4 patient deaths temporally related to contrast injection
Perflutren-based compounds contraindicated for use in patients with:
1. Acute coronary syndromes
2. Acute myocardial infarction
3. Worsening or clinically unstable heart failure
http://www.fda.gov/cder/drug/InfoSheets/HCP/microbubbleHCP.htm

“PSEUDOCOMPLICATION”
• Main ML, Goldman JH, and Grayburn PA. Thinking outside the “Box”—the ultrasound contrast
controversy. J Am Coll Cardiol 2007; 50 (25): 2434-2437.
• Complications occurring after a medical procedure may be due to either the procedure itself or due
to progression of the underlying disease state
• Major cardiovascular events are more likely to occur in patients who are “ill enough” to require
diagnostic testing
• Echocardiography often the test of choice (or the only test available) for critically ill patients
(shock, hypotension, tamponade, etc.)
• Association of adverse events following contrast administration does not establish causality

The present FDA documents for both definity and optison state that these products are not to be
administered to patients in whom the following conditions are known or suspected:
1.Right-to-left, bidirectional, or transient right-to-left cardiac shunts;
2.Hypersensitivity to perflutren; and
3.Hypersensitivity to blood, blood products, or albumin (applies to optison only).
• The intra-arterial injection of ultrasound contrast agents also is contraindicated.
• Additional monitoring of vital signs, electrocardiography, and cutaneous oxygen saturation (for 30
minutes) is not required in all patients but is now limited to patients with pulmonary hypertension
or unstable cardiopulmonary conditions.

Use Of Ultrasound Contrast Agents In PHT
• The FDA had initially considered PHT as a contraindication for IV UCAS.
• unshelled microbubbles administered intravenously could result in progressive drops in
arterial saturation, cardiac output, and stroke volume, with increases in pulmonary
vascular resistance and pulmonary artery pressure.
• The current UCAS approved by the FDA are composed of high–molecular weight gases
and various types of shells that remain relatively stable in circulation and for the most part
are <10 mm.
• In patients with PHT by improving the evaluation of regional right ventricular wall.
• Doppler image quality, especially the tricuspid regurgitant jet that is used to estimate
pulmonary artery systolic pressure.

Short-and long-term outcomes after both IV Optison and Definity injections
inpatients with varying severity of PHT
.
.
Abdelmoneim et al

INDICATIONS
Agitated saline contrast echocardiography
•Evaluation for right-to-left intracardiac shunt (enlarged right heart, ASD/PFO).
•Diagnosis of persistent left-sided SVC.
•Evaluate for PFO as a potential source of cerebral embolic phenomena (stroke, TIA).
Transpulmonary contrast echocardiography
•Poor left heart endocardial border visualization
•Diagnosis of left ventricular apical thrombus

CONTRAINDICATIONS
Saline and transpulmonary contrast echocardiography:
•Known large intracardiac shunt
•Pregnancy
Transpulmonary contrast echocardiography:
•Hypersensitivity to perflutren
•Severe pulmonary hypertension (relative contraindication)

FUTURE PERSPECTIVE
• SonoVue is a lipid-encapsulated sulfur hexafluoride–containing microbubble that also is
administered as an infusion or as small boluses during real-time very low MI imaging.
• 3D contrast echo

pre and post transplant echo , contrast echo

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