Ultrasound-enhanced systemic thrombolysis

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Ultrasound-enhanced systemic thrombolysis
Other namesSonothrombolysis
Specialty Radiology, neurology, cardiology

Ultrasound enhanced systemic thrombolysis (UEST), also known as sonothrombolysis, is a method that uses ultrasound waves to mechanically break the thrombi, or clots, using the vibration carried via soundwaves. [1] One major advantage of using ultrasound versus systemic thrombolysis is a reduced risk of bleeding, and improved heart function in the case of pulmonary embolism. [2]

Contents

Background

A large portion of initial research was conducted by Christy Holland, a Professor at the University Cincinnati and the Director of the University of Cincinnati Heart, Lung, and Vascular Institute, who also holds the patent for use of transcranial ultrasound in stroke patients. [3] One of the main studies characterizing the use of UEST in the setting of acute stroke was the CLOTBUST Trial, which was published in 2004 in the Journal of Neuroimaging. [4] Since then, research with UEST has explored its use in other thrombotic scenarios such as pulmonary embolism and deep vein thrombosis.

Mechanism

UEST works by using ultrasound waves at different frequencies as an additional treatment that works with the conventional thrombolytics such as tissue plasminogen activator (tPA). Typically, frequencies are in the megahertz (MHz) range, [5] however, some studies suggest that there is no statistically significant difference in frequency use 2 MHz or <2 MHz in the setting of ischemic stroke. [6]

Various Uses

Ischemic stroke

Transcranial Doppler ultrasound was first investigated in 2004, and demonstrated a significant clinical recovery through the use of sonothrombolysis with tPA, specifically through arterial recanalization. [4] Of note, it is important to first rule out hemorrhagic stroke prior to the initiation of thrombolysis. A meta-analysis conducted in 2020 investigating the safety and efficacy of sonothromoblysis in 5 randomized controlled trials demonstrated that there was overall benefit to using sonothrombolysis especially in the setting of a middle cerebral artery occlusion. [7]

Pulmonary Embolism

Another frequent condition that may require thrombolysis is a pulmonary embolism (PE), which is when a clot forms in a vein and travels to the lung vasculature, or forms directly in the lung vasculature. In certain patients with more severe forms of PE (massive or submassive), sonothrombolysis can improve cardiopulmonary function and reduce the bleeding risk that is accompanied by systemic thrombolysis. [8] Ultrasound has been shown to be more effective in reversing the damage to the right heart from strain due to the PE, and can help return the right heart to the appropriate size, when compared to just anticoagulation. [9]

Deep Vein Thrombosis

Studies examining the use of ultrasound enhanced thrombolysis for the treatment of deep vein thromboses (DVTs), or a clot located in the veins, are a bit more sparse, with only 1 randomized control trial up to 2018, and with many retrospective studies. A meta-analysis in 2018 looked at the efficacy of ultrasound and found that a large majority achieved significant thrombolysis, which they defined as >50% of the clot. The safety profile was also characterized in this study, and found that it was a relatively safe invasive procedure with only 1 death in 512 procedures and only 3.9% risk of significant bleeding. [10]

Cardiac Disease

The use of ultrasound in acute cardiac disease, such as a heart attack, is still in the early stages of investigation. However, recent data does demonstrate that in patients with an ST-segment elevation myocardial infarction (STEMI), sonothrombolysis may improve flow within the impacted vessels allowing for better cardiac muscle oxygenation. The use of ultrasound was also shown to have improved left heart function several months after the acute event. [11]

Limitations and Future Directions

While there is a lot of promise in the use of sonothrombolysis, there are limitations at this time. For example, in the setting of ischemic stroke, patients with MCA territory stroke benefit the most. Moreover, the thickness of the temporal bone may also reduce efficacy of sonothrombolysis. [12] With regard to use in cardiac disease, the coronary arteries are much more difficult to visualize with ultrasound for several reasons including obstructions and movement of the arteries while the heart contracts and relaxes. [13]

As ultrasound technology advances, the applications continue to expand. For instance, the use of a mobile ultrasound that can pair to mobile devices could be used instead of a bulky machine, which could allow for increased access to the technology. [14] Additionally, as the technology advances, there could be potential for sonothrombolysis to replace conventional thrombolytics given its safer side-effect profile and good efficacy.

See also

Related Research Articles

<span class="mw-page-title-main">Thrombosis</span> Formation of blood clots inside the blood vessels

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus.

<span class="mw-page-title-main">Pulmonary embolism</span> Blockage of an artery in the lungs

Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. Symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. Signs of a PE include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. Severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death.

<span class="mw-page-title-main">Venous thrombosis</span> Blood clot (thrombus) that forms within a vein

Venous thrombosis is the blockage of a vein caused by a thrombus. A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to lodge there, it becomes a pulmonary embolism (PE), a blood clot in the lungs. The conditions of DVT only, DVT with PE, and PE only, are all captured by the term venous thromboembolism (VTE).

Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause.

<span class="mw-page-title-main">Ischemia</span> Restriction in blood supply to tissues

Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism. Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue i.e. hypoxia and microvascular dysfunction. It also implies local hypoxia in a part of a body resulting from constriction.

<span class="mw-page-title-main">Thrombolysis</span> Breakdown (lysis) of blood clots formed in blood vessels, using medication

Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism.

<span class="mw-page-title-main">Tissue-type plasminogen activator</span> Protein involved in the breakdown of blood clots

Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots. It acts as an enzyme to convert plasminogen into its active form plasmin, the major enzyme responsible for clot breakdown. It is a serine protease found on endothelial cells lining the blood vessels. Human tPA is encoded by the PLAT gene, and has a molecular weight of ~70 kDa in the single-chain form.

<span class="mw-page-title-main">Deep vein thrombosis</span> Formation of a blood clot (thrombus) in a deep vein

Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enlarged veins in the affected area, but some DVTs have no symptoms.

<span class="mw-page-title-main">Interventional cardiology</span> Catheter-based treatment of structural heart diseases

Interventional cardiology is a branch of cardiology that deals specifically with the catheter based treatment of structural heart diseases. Andreas Gruentzig is considered the father of interventional cardiology after the development of angioplasty by interventional radiologist Charles Dotter.

<span class="mw-page-title-main">Coronary thrombosis</span> Medical condition

Coronary thrombosis is defined as the formation of a blood clot inside a blood vessel of the heart. This blood clot may then restrict blood flow within the heart, leading to heart tissue damage, or a myocardial infarction, also known as a heart attack.

<span class="mw-page-title-main">Alteplase</span> Thrombolytic medication

Alteplase, sold under the brand name Activase among others, is a biosynthetic form of human tissue-type plasminogen activator (t-PA). It is a thrombolytic medication used to treat acute ischemic stroke, acute ST-elevation myocardial infarction, pulmonary embolism associated with low blood pressure, and blocked central venous catheter. Alteplase is given by injection into a vein or artery. Alteplase is the same as the normal human plasminogen activator produced in vascular endothelial cells and is synthesized via recombinant DNA technology in Chinese hamster ovary cells (CHO). Alteplase causes the breakdown of a clot by inducing fibrinolysis.

<span class="mw-page-title-main">Cerebral infarction</span> Stroke resulting from lack of blood flow

Cerebral infarction, also known as an ischemic stroke, is the pathologic process that results in an area of necrotic tissue in the brain. In mid to high income countries, a stroke is the main reason for disability among people and the 2nd cause of death. It is caused by disrupted blood supply (ischemia) and restricted oxygen supply (hypoxia). This is most commonly due to a thrombotic occlusion, or an embolic occlusion of major vessels which leads to a cerebral infarct. In response to ischemia, the brain degenerates by the process of liquefactive necrosis.

An embolus, is described as a free-floating mass, located inside blood vessels that can travel from one site in the blood stream to another. An embolus can be made up of solid, liquid, or gas. Once these masses get "stuck" in a different blood vessel, it is then known as an "embolism." An embolism can cause ischemia—damage to an organ from lack of oxygen. A paradoxical embolism is a specific type of embolism in which the embolus travels from the right side of the heart to the left side of the heart and lodges itself in a blood vessel known as an artery. Thus, it is termed "paradoxical" because the embolus lands in an artery, rather than a vein.

Tenecteplase, sold under the trade names TNKase, Metalyse and Elaxim, is an enzyme used as a thrombolytic drug.

<span class="mw-page-title-main">Myocardial infarction</span> Interruption of cardiac blood supply

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction to the heart muscle. The most common symptom is retrosternal chest pain or discomfort that classically radiates to the left shoulder, arm, or jaw. The pain may occasionally feel like heartburn. This is the dangerous type of Acute coronary syndrome.

Embolectomy is the emergency interventional or surgical removal of emboli which are blocking blood circulation. It usually involves removal of thrombi, and is then referred to as thromboembolectomy or thrombectomy. Embolectomy is an emergency procedure often as the last resort because permanent occlusion of a significant blood flow to an organ leads to necrosis. Other involved therapeutic options are anticoagulation and thrombolysis.

<span class="mw-page-title-main">Acute limb ischaemia</span> Occurs when there is a sudden lack of blood flow to a limb

Acute limb ischaemia (ALI) occurs when there is a sudden lack of blood flow to a limb within 14 days of symptoms onset. On the other hand, when the symptoms exceed 14 days, it is called critical limb ischemia (CLI). CLI is the end stage of peripheral vascular disease where there is still some collateral circulation that bring some blood flow to the distal parts of the limbs. While limbs in both acute and chronic limb ischemia may be pulseless, a chronically ischemic limb is typically warm and pink due to a well-developed collateral artery network and does not need emergency intervention to avoid limb loss, whereas ALI is a vascular emergency.

<span class="mw-page-title-main">Arterial embolism</span> Interruption of blood flow to an organ

Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmonary embolism is classified as arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins. Arterial embolism is the major cause of infarction.

<span class="mw-page-title-main">Left ventricular thrombus</span> Medical condition

Left ventricular thrombus is a blood clot (thrombus) in the left ventricle of the heart. LVT is a common complication of acute myocardial infarction (AMI). Typically the clot is a mural thrombus, meaning it is on the wall of the ventricle. The primary risk of LVT is the occurrence of cardiac embolism, in which the thrombus detaches from the ventricular wall and travels through the circulation and blocks blood vessels. Blockage can be especially damaging in the heart or brain (stroke).

<span class="mw-page-title-main">Arterial occlusion</span>

Arterial occlusion is a condition involving partial or complete blockage of blood flow through an artery. Arteries are blood vessels that carry oxygenated blood to body tissues. An occlusion of arteries disrupts oxygen and blood supply to tissues, leading to ischemia. Depending on the extent of ischemia, symptoms of arterial occlusion range from simple soreness and pain that can be relieved with rest, to a lack of sensation or paralysis that could require amputation.

References

  1. ↑ Bader, Kenneth B.; Gruber, Matthew J.; Holland, Christy K. (January 2015). "Shaken and Stirred: Mechanisms of Ultrasound-Enhanced Thrombolysis". Ultrasound in Medicine & Biology. 41 (1): 187–196. doi:10.1016/j.ultrasmedbio.2014.08.018. PMC   4258471 . PMID   25438846.
  2. ↑ Stępniewski, Jakub; Kopeć, Grzegorz; Musiałek, Piotr; Magoń, Wojciech; Jonas, Kamil; Waligóra, Marcin; Sobczyk, Dorota; Podolec, Piotr (February 2021). "Hemodynamic Effects of Ultrasound-Assisted, Catheter-Directed, Very Low-Dose, Short-Time Duration Thrombolysis in Acute Intermediate–High Risk Pulmonary Embolism (from the EKOS-PL Study)". The American Journal of Cardiology. 141: 133–139. doi:10.1016/j.amjcard.2020.11.004. PMID   33220318. S2CID   227124304.
  3. ↑ "Cardiovascular Insights | Ultrasound-Mediated Thrombolysis May Offer Promise | Cardiovascular Insights". 2015-08-10. Retrieved 2022-01-09.
  4. 1 2 Alexandrov, Andrei V.; Wojner, Anne W.; Grotta, James C.; CLOTBUST Investigators (April 2004). "CLOTBUST: design of a randomized trial of ultrasound-enhanced thrombolysis for acute ischemic stroke". Journal of Neuroimaging. 14 (2): 108–112. doi:10.1111/j.1552-6569.2004.tb00225.x. ISSN   1051-2284. PMID   15095554. S2CID   24432003.
  5. ↑ Pfaffenberger, Stefan; Devcic-Kuhar, Branka; El-Rabadi, Karem; Gröschl, Martin; Speidl, Walter S.; Weiss, Thomas W.; Huber, Kurt; Benes, Ewald; Maurer, Gerald; Wojta, Johann; Gottsauner-Wolf, Michael (March 2003). "2MHz ultrasound enhances t-PA-mediated thrombolysis: comparison of continuous versus pulsed ultrasound and standing versus travelling acoustic waves". Thrombosis and Haemostasis. 89 (3): 583–589. doi:10.1055/s-0037-1613390. ISSN   0340-6245. PMID   12624644. S2CID   24121476.
  6. ↑ Zafar, Marium; Memon, Roha Saeed; Mussa, Muhammad; Merchant, Rameez; Khurshid, Aiman; Khosa, Faisal (August 2019). "Does the administration of sonothrombolysis along with tissue plasminogen activator improve outcomes in acute ischemic stroke? A systematic review and meta-analysis". Journal of Thrombosis and Thrombolysis. 48 (2): 203–208. doi: 10.1007/s11239-019-01899-6 . ISSN   1573-742X. PMID   31214876. S2CID   190656705.
  7. ↑ Li, Xiaoqiang; Du, Hui; Song, Zhibin; Wang, Hui; Tan, Zhijian; Xiao, Mufang; Zhang, Fu (September 2020). "Efficacy and safety of sonothrombolysis in patients with acute ischemic stroke: A systematic review and meta-analysis". Journal of the Neurological Sciences. 416: 116998. doi: 10.1016/j.jns.2020.116998 . PMID   32623143. S2CID   220057371.
  8. ↑ Pei, Dorothy T.; Liu, Jing; Yaqoob, Maidah; Ahmad, Waqas; Bandeali, Salman S.; Hamzeh, Ihab R.; Virani, Salim S.; Hira, Ravi S.; Lakkis, Nasser M.; Alam, Mahboob (2019-11-01). "Meta-Analysis of Catheter Directed Ultrasound-Assisted Thrombolysis in Pulmonary Embolism". The American Journal of Cardiology. 124 (9): 1470–1477. doi:10.1016/j.amjcard.2019.07.040. ISSN   1879-1913. PMID   31492420. S2CID   201165424.
  9. ↑ Mangi, Muhammad A.; Rehman, Hiba; Bansal, Vikas; Zuberi, Omer (2017-07-19). "Ultrasound Assisted Catheter-Directed Thrombolysis of Acute Pulmonary Embolism: A Review of Current Literature". Cureus. 9 (7): e1492. doi: 10.7759/cureus.1492 . ISSN   2168-8184. PMC   5605122 . PMID   28944131.
  10. ↑ Shi, Yadong; Shi, Wanyin; Chen, Liang; Gu, Jianping (April 2018). "A systematic review of ultrasound-accelerated catheter-directed thrombolysis in the treatment of deep vein thrombosis". Journal of Thrombosis and Thrombolysis. 45 (3): 440–451. doi:10.1007/s11239-018-1629-y. ISSN   1573-742X. PMID   29417407. S2CID   3859406.
  11. ↑ Porter, Thomas R.; Mathias, Wilson (2019-07-25). "Cardiovascular Sonothrombolysis". Current Cardiology Reports. 21 (8): 86. doi:10.1007/s11886-019-1167-z. ISSN   1534-3170. PMID   31342183. S2CID   198195472.
  12. ↑ Chen, Zhouqing; Xue, Tao; Huang, Huachen; Xu, Jiayi; Shankar, Sandhya; Yu, Hao; Wang, Zhong (2019-01-09). "Efficacy and safety of sonothombolysis versus non-sonothombolysis in patients with acute ischemic stroke: A meta-analysis of randomized controlled trials". PLOS ONE. 14 (1): e0210516. Bibcode:2019PLoSO..1410516C. doi: 10.1371/journal.pone.0210516 . ISSN   1932-6203. PMC   6326494 . PMID   30625224.
  13. ↑ Kaul, Sanjiv (2009-03-17). "Sonothrombolysis: a universally applicable and better way to treat acute myocardial infarction and stroke? Who is going to fund the research?". Circulation. 119 (10): 1358–1360. doi: 10.1161/CIRCULATIONAHA.108.846113 . ISSN   1524-4539. PMID   19255337.
  14. ↑ Zeldovich, Lina. "Handheld Ultrasound Devices Are Speeding Diagnosis of COVID-19". Scientific American. Retrieved 2022-01-09.
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