Endomyocardial Biopsy

Overview

Endomyocardial biopsy (EMB) is a routine invasive surgery used to acquire small samples of heart muscle, particularly to identify donor heart rejection following heart transplantation. It is also used to diagnose some cardiac problems.

A bioptome is a device that allows access to the heart through a sheath put into the right internal jugular or, less commonly, the femoral vein. Monitoring throughout the surgery includes taking ECGs and blood pressures. Echocardiography or fluoroscopy is used to guide and confirm the correct positioning of the bioptome.

When performed by a qualified physician at a specialized center, the chance of problems is less than 1%. Heart perforation with pericardial tamponade, haemopericardium, AV block, tricuspid regurgitation, and pneumothorax are all serious consequences.

 

The Layers of the Heart Wall

The heart wall is made up of connective tissue, endothelium, and cardiac muscle. The cardiac muscle permits the heart to contract and the heartbeat to be synchronized. The heart wall is separated into three layers: epicardium, myocardium, and endocardium.

• Epicardium: the outer protective layer of the heart.
• Myocardium: muscular middle layer walls of the heart.
• Endocardium: the inner layer of the heart.

 

Epicardium:

The outer layer of the heart wall is known as the epicardium (epi-cardium). It is also known as visceral pericardium since it constitutes the pericardium's inner layer. The epicardium is mostly made up of loose connective tissue, such as elastic fibers and adipose tissue. 

The epicardium protects the inner heart layers and contributes to the formation of pericardial fluid. This fluid fills the pericardial cavity and helps to minimize pericardial membrane friction. The coronary blood arteries, which provide blood to the heart wall, are also located in this cardiac layer. The epicardium's inner layer is in direct touch with the myocardium.

Myocardium:

The myocardium (myo-cardium) is the heart's middle layer. It is made up of cardiac muscle fibers that allow the heart to contract. The myocardium is the thickest layer of the heart wall, ranging in thickness across the heart. The myocardium of the left ventricle is the thickest because it generates the power required to pump oxygenated blood from the heart to the rest of the body. Cardiac muscle contractions are controlled by the peripheral nervous system, which also controls involuntary activities such as heart rate.

Specialized myocardial muscle fibers provide for cardiac conduction. These fiber bundles, which include the atrioventricular bundle and Purkinje fibers, transport electrical impulses from the heart's center to the ventricles. These impulses cause the ventricular muscle fibers to contract.

Endocardium:

The endocardium (endo-cardium) is the heart's thin inner layer. This layer borders the inner chambers of the heart, covers the heart valves, and connects to the endothelium of big blood vessels. Smooth muscle and elastic fibers make up the endocardium of the cardiac atria.

Endocarditis is a disorder caused by an infection of the endocardium. Endocarditis is often caused by a bacterial, fungal, or other microbe infection of the heart valves or endocardium. Endocarditis is a potentially deadly disease.

 

Who Performs a Heart Biopsy?

A cardiologist is the person who does cardiac biopsies. This physician has received extensive training in the use of catheter-based techniques to diagnose and treat cardiac issues.

To perform this procedure, your doctor will thread a catheter (a thin, flexible tube) into blood vessels. This procedure is known as cardiac catheterization.

 

Indications & Patient Selection

EMB indications can be divided into two broad categories: transplant and non-transplant.

Among transplant patients:

1. Surveillance EMB is used to detect allograft rejection before clinically significant cardiac dysfunction develops as a result of rejection.
2. Because allograft rejection is more common in the first 6 to 12 months, most programs conduct it as part of a protocol in the first year.
3. Although there is no standard or agreed-upon schedule for surveillance biopsy, most institutions do numerous biopsies during the first 6 to 12 months; beyond that, the frequency varies per facility.
4. Biopsies are also conducted when there are clinical concerns about transplant rejection (e.g., an asymptomatic drop in ejection fraction) or when there are major changes in immunosuppression.

 

In non-transplant patients:

• In the non-transplant setting, the most common indication for EMB is to confirm a clinically suspected disease rather than as part of a regular examination of new onset cardiomyopathy or heart failure.
• The ACC/AHA Class I indications for EMB are focused on determining the etiology of acute onset fulminant heart failure, namely giant cell myocarditis. Other types of myocarditis, such as lymphocytic and hypersensitivity, might provide this clinical presentation.
• The two Class I indications (described as clinical scenarios) according to the ACC/AHA guidelines are: 

1. New-onset heart failure (2 weeks duration) with hemodynamic compromise in the context of normal or dilated left ventricle (LV).
2. New-onset heart failure lasting 2 to 12 weeks, with new ventricular arrhythmias, second or third degree heart block, or failure to respond to standard treatments within 1 to 2 weeks after treatment initiation.

 

• In individuals with a clinical suspicion of cardiac sarcoidosis, hypersensitivity myocarditis, anthracycline toxicity, or intracardiac tumors, EMB is reasonable (e.g., Class II) (excluding typical myxomas).
• EMB is acceptable in children with unexplained cardiomyopathy and in adults with unexplained restricted cardiomyopathy.
• When suspected clinically, EMB can be decisive in the diagnosis of amyloidosis, hemochromatosis, endocardial fibroelastosis, and Loeffler's disease.

 

Endomyocardial Biopsy Contraindications

Routine use of EMB for new heart failure is not advised by any society since the diagnostic yield is minimal and the clinical benefit is exceeded by the procedure's danger.

Uncorrected coagulopathies, thrombocytopenia, insufficient vascular access, and mechanical prosthetic tricuspid valve are relative contraindications.

 

How EMB is Performed?

Pre-procedural assessment:

• In order to acquire informed consent from the patient or designated authority, the indications, alternative procedures, and risks/benefits of EMB should be discussed.
• A detailed history and physical examination should be performed, as well as a current laboratory assessment (renal function, serum electrolytes, complete blood count, and coagulation profile).
• Prior EMB experiences of the patient are critical, especially when several serial procedures are performed during transplantation.
• It is critical to pay close attention to the vascular access site (e.g., jugular or femoral vein). The right internal jugular route is preferred because it allows the bioptome to be guided to particular regions inside the heart and allows the patient to ambulate and be released quickly after the treatment.

 

Patient preparation:

• Noninvasive continuous monitoring of blood pressure, oximetry, and cardiac rhythm is advised.
• EMB does not usually necessitate sedation. However, if sedation is deemed required, conscious sedation typically suffices.

 

Procedure:

• Right ventricular biopsies are most usually conducted by the right internal jugular vein (IJ(, followed by the right or left femoral vein; subclavian access and the left IJ can also be utilized. A femoral artery route is most typically used for left ventricular biopsies.
• EMB can be conducted under fluoroscopic or echocardiographic supervision.
• With the patient's head rotated to the left, locate the clavicular and sternal heads of the sternocleidomastoid muscle (SCM); allowing the patient to lift his or her head off the table assists identification of these muscle groups. Palpation should also be used to locate the carotid artery.
• % Xylocaine is used to anesthetize the apex of the triangle formed by the SCM heads. A single needle is directed immediately lateral to the palpated carotid artery and toward the ipsilateral nipple.
• Ultrasound guidance, which provides direct view of the vein, may improve IJ cannulation success. Some operators choose a micropuncture needle to reduce the implications of unintentional carotid artery puncture.
• After being cannulated, an 11 cm 7-Fr sheath is inserted within the IJ vein and superior vena cava to allow passage of a pulmonary arterial catheter and bioptome. To minimize TV damage, some centers utilize longer sheaths that cross the tricuspid valve (TV).
• If needed, hemodynamics can be obtained before to the actual biopsy.
• Under fluoroscopic guidance, a disposable, preshaped, semirigid, 50-cm bioptome is inserted via the vascular sheath into the right atrium and appropriately pointed toward the right atrial (RA) lateral wall.
• A counterclockwise motion directs the bioptome anteriorly toward and across the TV into the right ventricle as it advances through the right atrium (RV). The bioptome is further rotated and advanced counterclockwise toward the apical septum.
• Premature ventricular contractions should be used to confirm position in the RV; apical position should be assessed in the right anterior oblique (RAO) projection; and septal positioning should be confirmed in the 60-degree left anterior oblique (LAO) projection with the bioptome pointed posteriorly.
• When the bioptome is suitably positioned, it is withdrawn slightly with the jaws open and then readvanced to the septum until minimal resistance is met and PVCs begin. To obtain the specimen, the jaws are then closed. After removing the bioptome from the sheath, the sample is extracted and put in a fixation solution.
• Multiple passes with the bioptome are recommended for taking biopsies from the apical RV septum. Ideally, the specimens should be 2 to 3 mm3. Macroscopically, myocardial tissue may be recognized from fat or scar by its beefy red color.
• For appropriate sampling, at least 3 to 5 biopsy samples should be collected; more may be required depending on the research indication.
• Specimens are frequently stained and histologically examined. Electron microscopy and/or protein or molecular analyses may be sought in exceptional circumstances.
• At the time of the biopsy, specific tissue stains for certain diseases (e.g., Congo red for amyloid) should be ordered, and coordination with the cardiac pathologist is necessary. Electron microscopy may be very useful in situations like Fabry's disease and muscular dystrophies.

 

Femoral vein approach:

• The femoral vein can be reached by palpating the femoral artery pulse at the fluoroscopically determined femoral head and inserting the needle roughly 1 cm inferior and medial from the pulse.
• A long, 7-Fr preformed sheath with a main distal curve is inserted into the apex of the RV, aided by a pigtail catheter inserted into the long sheath. When the pigtail catheter is appropriately positioned, it is removed, leaving the prepared sheath in place.
• Because the bioptome cannot be directed independently of the sheath tip's location, sampling is confined to the sheath's distal position when using the femoral vein technique.
• After flushing of the long sheath, a long (105 cm) flexible bioptome is advanced through the sheath into the RV. The jaws are opened as soon as it exits the sheath to avoid RV perforation and advanced to the septum. Samples are then obtained as described above.

 

Post-procedure:

Before removing the venous sheath, the central venous pressure (CVP) and blood pressure should be measured. When compared to preprocedural data, a significant rise in CVP and loss of the Y descent should raise concerns about RV perforation and tamponade.

It is not necessary to perform routine post-procedural echocardiographic imaging.

After a brief period of monitoring, most patients who have undergone a proper 

 

Benefits & Advantages of Endomyocardial Biopsy

• The sensitivity and specificity of EMB vary depending on the clinical entity being identified. For particular disorders, specificity is high (e.g., amyloidosis) while sensitivity is poor (e.g., sarcoidosis).
• A specific diagnosis is determined just 20% of the time based on biopsy data alone, although this rises when other clinical symptoms are included. Because there is another "gold standard" to compare to, true specificities and sensitivities are difficult to determine.
• Sensitivities presented in the literature include: giant cell myocarditis >80%, lymphocytic myocarditis 10% to 35%, and cardiac sarcoidosis roughly 20%.
• In general, the specificity and sensitivity of a particular diagnosis in the assessment of dilated cardiomyopathy are generally poor.
• The sensitivity of EMB is reduced by sampling error. Pre-procedural cardiac MRI is recommended by several authorities to increase sensitivity.

 

Alternative/ Additional Procedures to Consider

Cardiac magnetic resonance imaging (MRI)

• In most cases, cardiac MRI is useful adjunct rather than a substitute for EMB.
• In individuals with suspected cardiac tumors, MRI should be examined before proceeding to EMB.
• If biopsy samples are collected from areas of contrast enhancement, MRI may increase EMB sensitivity.
• Although MRI with late gadolinium can be used to detect myocarditis (e.g., midwall, nonvascular hyperenhancement), EMB is necessary to establish specific histologic diagnoses (e.g., lymphocytic versus giant cell myocarditis).
• In individuals with myocarditis, MRI may be utilized to assess therapy success.
• Because of its low specificity and sensitivity, MRI cannot replace EMB for monitoring transplant rejection.
• MRI may be considered in the setting of a negative EMB if there is a strong suspicion for myocarditis or other conditions such as sarcoidosis.

 

Gene-expression profiling:

• Gene-expression profiling (e.g., Allomap) can be employed for rejection surveillance in post-transplant patients who are at low risk of rejection.

 

Heart Biopsy Recovery Time

For a few hours, healthcare experts will monitor your recovery and look for symptoms of difficulties. During this period, you will be subjected to chest X-rays to search for symptoms of probable problems such as:

• Lung collapse (pneumothorax).
• Hemothorax (a hemorrhage that causes blood to pool between the chest wall and lungs).

Do not move anything heavy or engage in intense activity for 24 hours following the operation. The next day, you should be able to resume work and normal activities.

 

Complications & Management

Complications rates are uncommon and rarely (<1%) fatal in experienced hands. Access-related injuries such as venous thrombosis, carotid cannulation, hemorrhage, nerve palsy, air embolism, and pneumothorax are the most prevalent consequences. The use of sonographic-guided entry procedures may help to reduce such difficulties.

Self-limited arrhythmias, most often premature atrial contractions (PACs), premature ventricular contractions (PVCs), and non-sustained ventricular tachycardia (NSVT), are common and seldom need intervention. Ventricular tachycardia, ventricular fibrillation, atrial fibrillation, and AV block may occur on rare occasions.

Although myocardial perforation is infrequent, it should be considered if there is any chest discomfort or acute hemodynamic instability during the surgery.

Obtaining specimens from the RV apical septum and employing biplane confirmation of bioptome location before to closing the bioptome jaws are the most effective ways to prevent myocardial puncture. This problem may be reduced with echocardiographic supervision.

If myocardial perforation is suspected, confirm it by fluoroscopy of the heart boundaries, echocardiography, and/or right atrial pressure measurement.

Although many individuals with myocardial perforation can be treated conservatively with hospitalization and monitoring, cardiac tamponade necessitates immediate pericardiocentesis and cardiac surgical consultation.

Tricuspid valve regurgitation can arise as a result of an unintentional biopsy of the valve leaflets or chordae, especially after many surgeries (e.g. following heart transplantation).

This problem can be reduced by using a longer sheath to carry the bioptome over the TV, echocardiographic guidance, and sampling from the RV apical septum.

Inadvertent biopsy of another organ (e.g., liver), damage to the coronary sinus, and formation of septal perforator artery-to-right ventricle AV fistulas are all rare consequences.

 

When Should I Call My Doctor?

You should call your healthcare provider if you experience:

• Dizziness.
• Irregular pulse and heart rate.
• Shortness of breath or breathing problems.
• Symptoms of a heart attack, like chest pain.
• Signs of a stroke, such as paralysis in one part of your body or inability to speak.
• Signs of infection, like fever or chills.

 

Conclusion

The significance and value of endomyocardial biopsy (EMB) in the work-up of cardiovascular disorders is still disputed, and practice varies greatly between facilities. EMB is a diagnostic method used to examine various heart problems where non-invasive testing cannot generally generate a clinical diagnosis.

Biopsies are not without risk, and for some purposes, less invasive diagnostic methods such as cardiac magnetic resonance imaging (MRI) or positron emission tomography (PET) scans outperform EMB. 

However, there are some settings and scenarios in which an EMB might be useful in establishing a diagnosis when no other diagnostic test gives a significant result.

As with every diagnostic modality, the EMB procedure has unique characteristics in terms of sensitivity, specificity, and predictive values for different diseases.