A Review of Non-Invasive Acoustic Reperfusion Technologies for STEMI
Main Article Content
Abstract
St-Elevation Myocardial Infarction (STEMI), commonly an acute, occlusive blood clot in a major epicardial coronary artery, is the most serious of heart attacks, carrying a significant mortality and morbidity, and opening the occluded artery quickly with good distal reflow is the goal for best clinical outcomes. Slow arrival of Emergency Health Services (EHS), a lack of Cathlab availability in underdeveloped and rural areas, poor performance and bleeding risks with thrombolytic drug therapy, and a high rate of poor microvascular re-flow regardless of therapy, have prompted searches for alternative or adjunctive treatments.
Mechanical forces or pressure waves imparted to the human body (herein described as “Acoustic Therapies”) have been well studied both in vitro and in catheter-based systems in their abilities to increase blood flow and disrupt and clear blood clots. However, the search for a non-invasive acoustic therapy suitable for first-line response in the treatment of acute thrombotic arterial occlusions, including STEMI, remains elusive. Indeed, due to the vast differences of acoustic penetration windows and variabilities of at-risk adjacent tissues, there has been a historic dilemma of “threading the needle” in finding a workable waveform and mode of delivery that is intense enough to provide adequate penetration with a clot-disruptive effect, while also avoiding harm to the patient.
STEMI victims who reach professional care in view of Primary Percutaneous Coronary Intervention (PPCI) or pre-hospital IV thrombolysis, reportedly have a ~ 4-10% resultant in-hospital mortality, with the number approaching 50% if complicated by cardiogenic shock, hence there remains room for improvement. Indeed, acoustic reperfusion for STEMI could foreseeably add particular value as a stand-alone therapy or adjunctive to IV thrombolysis in rural or relatively poor areas where a Cardiac Cathlab is not readily available, as an early warning and treatment system for STEMI patients awaiting EHS, and, importantly, for treatment of the infamous "No-Reflow phenomenon" following PPCI, where many solutions have been tried and failed.
This paper provides a history and commentary on the various forwarded non-invasive acoustic STEMI reperfusion strategies to date, including High Frequency diagnostic UltraSound (HFUS) with IV Microbubbles (MBs) - a technique commonly referred to as "Sonothrombolysis", transcutaneous Low Frequency Ultrasound (LFUS), and little-known diastolic timed Low Frequency Vibration (dtLFV), which involves palpable, infrasonic to sonic frequency percussions to the chest wall as a stand-alone measure, or as an adjunct to IV thrombolysis. A discussion is provided on each of these therapies' challenges, how they could fit in the modern paradigm of care, and where they are along their respective research and development pathways.
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References
2. Ibanez B, James S, Agewall S, Antunes MJ, Halvorsen S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the Management of Acute Myocardial Infarction in Patients Presenting With ST-Segment Elevation of the European So
3. Sabe MA, Kaeberlein FJ, Sabe SA, Kelly A, Summerfield T, et al. Emergency Chest Pain Center: A Novel Approach to Reduce Door to Balloon Time. JACC Adv. 2025; 4: 101774.
4. Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The task force on the management of acute myocardial infarction of the European Society of Cardiology. Eur Heart J. 2003; 24: 28-66.
5. Bhandari M, Vishwakarma P, Sethi R, Pradhan A. Stroke Complicating Acute ST Elevation Myocardial Infarction Current Concepts. Int J Angiol. 2019; 28: 226-230.
6. Hillani A, Potter B: Intracoronary Thrombus and No-Reflow: one Size to Fit All? Canadian Journal of Cardiology. Feb 2021, Editorial, Vol 37, Issue 2, Pg. 202-205.
DOI:https//doi.org/10.1016/j.cjca.2020.08.015
7. Faridi KF, Wang Y, Minges KE, Smilowitz NR, McNamara RL, Kontos MC, Wang TY, Connors AC, Clary JM, Osborne AD, Pereira L, Curtis JP, Blankinship K, Mayfield J, Abbott JD. Predicting Mortality in Patients Hospitalized With Acute Myocardial Infarction: From the National Cardiovascular Data Registry. Circ Cardiovasc Qual Outcomes. 2025 Mar;18(3): e011259. doi: 10.1161/CIRCOUTCOMES.124.011259. Epub 2025 Jan 13. PMID: 39801472; PMCID: PMC1 1919567.
8. Annibali G, Scrocca I, Aranzulla TC, Meliga E, Maiellaro F, Musumeci G. "No-Reflow" Phenomenon: A Contemporary Review. J Clin Med. 2022 Apr 16;11(8):2233. doi: 10.3390/jcm11082233. PMID: 35456326; PMCID: PMC9028464.
9. American Heart Association, CPR Facts and Stats, American Heart Association CPR. Cares. Accessed November 2nd, 2025. https://mycares.net/sitepages/aboutcares.jsp
10. Fang J. Public awareness of heart attack symptoms. What should we look for and how will it help? Future Cardiology, 2010, Volume 6, Issue 5, pp 563 - 565.
11. Dickson, E. US patent No. 1612267, entitled, “Surgical Dressing”, 1925.
12. Russhard P, Al Janabi F, Parker M, Clesham GJ. Patterns of ST-segment resolution after guidewire passage and thrombus aspiration in primary percutaneous coronary intervention (PPCI) for acute myocardial infarction. Open Heart. 2016;3:e000430. https://doi.org/10.1136/openhrt-2016-000430
13. Wobser E, Stumpff U: Intragastral disintegration of blood coagula by mechanical vibration. Endoscopy 1978, 10:15–19. doi:10.1055/s-0028-1098254.
14. Dubrul, et al: Vibrating Catheter, US Patent No. 5,713,848, 1998.
15. Krajcer Z, Atmakuri, S. One step treatment with of DVT with the Trellis-8 Device. Apr. 2006, ENDOVASCULAR TODAY, pp. 69 -74.
16. Trubestein G., Engel C., Etzel F., Sobbe A., Cremer H., Stumpff U. Thrombolysis by ultrasound. Clin. Sci. Mol. Med. 1976;3:697s–698s. doi: 10.104 2/cs051697s.
17. Steffen W, Fishbein MC, Luo H, Lee DY, Nita H, Cumberland DC, Tabak SW, Carbone M, Maurer G, Siegel RJ. High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study. J Am Coll Cardiol. 1994;24:1571-1579.
18. Nedelmann, Max & Brandt, Christian & Schneider, Felicitas & Eicke, Martin & Kempski, Oliver & Krummenauer, Frank & Dieterich, Marianne. (2005). Ultrasound-Induced Blood Clot Dissolution without a Thrombolytic Drug Is More Effective with Lower Frequencies. Cerebrovascular diseases (Basel, Switzerland). 20. 18-22. 10.1159/000086122.
19. Tachibana K, Tachibana S. Albumin microbubble echo-contrast material as an enhancer for ultrasound accelerated thrombolysis. Circulation. 1995;92:1148–1150. doi: 10.1161/01.cir.92.5.1148.
20. Yao R, Hu J, Zhao W, Cheng Y, Feng C. A review of high-intensity focused ultrasound as a novel and non-invasive interventional radiology technique. J Interv Med. 2022 Jun 22;5(3):127-132. doi: 10.101 6/j.jimed.2022.06.004. PMID: 36317144; PMCID: PMC9617156.
21. Rosenschein U, Furman V, Kerner E, Fabian I, Bernheim J, Eshel Y. Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results. Circulation. 2000 Jul 11;102(2):238-45. doi: 10.1161/01.cir.102.2.238. PMID: 10889137.
22. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moyé LA, Hill MD, Wojner AW; CLOTBUST Investigators. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004 Nov 18;351(21):2170-8. doi: 10.1056/NEJMoa041175. PMID: 15548777.
23. Xie F, Lof J, Everbach C, He A, Bennett RM, Matsunaga T, Johanning J, Porter TR. Treatment of acute intravascular thrombi with diagnostic ultrasound and intravenous microbubbles. JACC Cardiovasc Imaging. 2009 Apr;2(4):511-8. doi: 10.1016/j.jcmg.2 009.02.002. PMID: 19580735.
24. Needs D, Blotter J, Cowan M, Fellingham G, Johnson AW, et al. Effect of Localized Vibration Massage on Popliteal Blood Flow. J Clin Med. 2023; 12: 2047.
25. Fateh HR, Nakhostin Ansari N, Nakhostin-Ansari A, et al. The effects of local calf vibration on balance, blood flow, and nerve conductivity in patients with diabetic peripheral neuropathy: a pilot study. Physiother Theory Pract Jul 2024;40(7):1397–1403. doi: 10.1080/09593985.2023.2173992
26. Liao F, Zhang K, Zhou L, Chen Y, Elliott J, Jan YK. Effect of Different Local Vibration Frequencies on the Multiscale Regularity of Plantar Skin Blood Flow. Entropy (Basel). Nov 13 2020;22(11)doi: 10.33 90/e 22111288
27. Espeit L, Lapole T. Effects of graduated compression stockings, local vibration and their combination on popliteal venous blood velocity. Phlebology. Aug 2020;35(7):505–512. doi: 10.117 7/0268355520902000
28. Ren W, Pu F, Luan H, et al. Effects of Local Vibration With Different Intermittent Durations on Skin Blood Flow Responses in Diabetic People. Front Bioeng Biotechnol 2019;7:310. doi: 10.3389/fbio e.2019.00310
29. Lindblad LE, Lorenz RR, Shepherd JT, Vanhoutte PM: Effect of vibration on canine cutaneous artery. Heart Circ Physiol 1986, 19:H519–H523.
30. Ljung B, Silvertsson R: Vibration-induced inhibition of vascular smooth muscle contraction. Blood Vessels 1975, 12:38–52.
31. Hudlicka O, Wright A: The effect of vibration on blood flow in skeletal muscle in rabbit. Clin Sci Mol Med 1978, 55:471–476.
32. Ichioka S, Yokogawa H, Nakagami G, Sekiya N, Sanada H: In vivo analysis of skin microcirculation and the role of nitric oxide during vibration. Ostomy Wound Manage. 2011 Sep; 57 (9): 40-7.
33. Maloney-Hinds C, Petrofsky JS, Zimmerman G, Hessinger DA: The role of nitric oxide in skin blood flow increases due to vibration in healthy adults and adults with type 2 diabetes. Diabetes Technol Ther 2009, 11(1):39–43. doi:10.1089/dia.2008.0011.
34. Pei Z, Chen J, Zhu M, Liu J, Zhang Q: The effects of infrasound on the secretion of the nitric oxide in rat plasma and the expression of VEGF in vascular endothelia. Chinese Heart Journal 2004, 1:20–22. doi:cnki:ISSN:1005-3271.0.2004-01-005.
35. Suchkova VN, Baggs RB, Sahni SK, Francis CW. Ultrasound improves tissue perfusion in ischemic tissue through a nitric oxide dependent mechanism. Thromb Haemost. 2002 Nov;88(5):865-70. PMID: 12428107.
36. Atar S, Siegel RJ, Akel R, Ye Y, Lin Y, Modi SA, Sewani A, Tuero E, Birnbaum Y. Ultrasound at 27 kHz increases tissue expression and activity of nitric oxide synthases in acute limb ischemia in rabbits. Ultrasound Med Biol. 2007 Sep;33(9):1483-8. doi: 10.1016/j.ultrasmedbio.2007.03.008. Epub 2007 May 16. PMID: 17507145.
37. Miyamoto T, Neuman Y, Luo H et al: Coronary vasodilation by noninvasive transcutaneous ultrasound—an in vivo canine study. J Am Coll Cardiol 2003; 41: 1623.
38. Iida K, Luo H, Hagisawa K, Akima T, Shah PK, Naqvi TZ, Siegel RJ. Noninvasive low-frequency ultrasound energy causes vasodilation in humans. J Am Coll Cardiol. 2006 Aug 1;48(3):532-7. doi: 10.1016/j.jacc.2006.03.046. Epub 2006 Jul 12. PMID: 16875980.
39. Okano S, Shimotori Y, Manabe Y, Shibata K, Uebaba K (2015) Changes of Cerebral Blood Flow by the Weak Trans-Cranial Ultrasound Irradiation in Healthy Adult Volunteers: Japanese Journal of Complementary and Alternative Medicine 12(2): 73-78.
40. Morishita K, Karasuno H, Yokoi Y, Morozumi K, Ogihara H, Ito T, Fujiwara T, Fujimoto T, Abe K. Effects of therapeutic ultrasound on intramuscular blood circulation and oxygen dynamics. J Jpn Phys Ther Assoc. 2014;17(1):1-7. doi: 10.1298/jjpta.Vol1 7_001. PMID: 25792902; PMCID: PMC4316550.
41. J. Todd Belcik. Augmentation of Muscle Blood Flow by Ultrasound Cavitation. Mediated by ATP and Purinergic Signaling. Circulation,Volume 135, Issue 13, 28 March 2017; Pages 1240-1252. https://doi.org/10.1161/circulationaha.116.02482
42. Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, Sedlaczek O, Koroshetz WJ, Hennerici MG. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005 Jul;36(7):1441-6. doi: 10.1 161/01.STR.0000170707.86793.1a. Epub 2005 Jun 9. PMID: 15947262.
43. Roos S.T., Juffermans L.J., van Royen N., et al. Unexpected high incidence of coronary vasoconstriction in the Reduction of Microvascular Injury Using Sonolysis (ROMIUS) Trial. Ultrasound Med Biol 2016;42:1919-1928.
44. Luo, H., Nishioka, T., Berglund, H. et al. Effect of external ultrasound frequency on thrombus disruption in vitro. J Thromb Thrombol 3, 63–66 (1996). https://doi.org/10.1007/BF00226413
45. Chen Y, Chang H, Chiang Y, Lin C. Application and development of ultrasonics in dentistry. Journal of the Formosan Medical Association, Volume 112, Issue 11, November 2013, Pages 659-665.
46. Eli Vlaisavljevich, Kuang-Wei Lin, Adam Maxwell, Matthew T. Warnez, Lauren Mancia, Rahul Singh, Andrew J. Putnam, Brian Fowlkes, Eric Johnsen, Charles Cain, Zhen Xu. Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation,Ultrasound in Medicine & Biology,Volume 41, Issue 6,2015, Pages 1651-1667,ISSN 0301-5629,
47. 45 Lavon I, Kost J. Ultrasound and transdermal drug delivery. Drug Discov Today. 2004;9(15):670–676. doi: 10.1016/S1359-6446(04)03170-8.
48. Graves J, Morgan D. New evidence for the inverse dependence of mechanical and chemical effects on the frequency of ultrasound. Ultrasonics Sonochemistry. Volume 18, Issue 1, January 2011, Pages 226-230.
49. Blinc, Ales & Francis, C & Trudnowski, J & Carstensen, E. (1993). Characterization of ultrasound-potentiated fibrinolysis in vitro. Blood. 81. 2636-43. 10.1182/blood.V81.10.2636.bloodjournal81102636.
50. Suchkova, V, Siddiqi F, Carstensen E, Dalecki D, Child S, Francis CW. Enhancement of Fibrinolysis With 40-kHz Ultrasound. Circulation. Volume 98, Issue 10, 8 September 1998; Pages 1030-1035. https://doi.org/10.1161/01.CIR.98.10.1030
51. Ueda H, Mutoh M, Seki T, et al. Acoustic cavitation as an enhancing mechanism of low-frequency sonophoresis for transdermal drug delivery. Biol Pharm Bull. 2009;32(5):916–920. doi: 10.1248/bp b.32.916.
52. Luo H, Nishioka T, Fishbein MC, Cercek B, Forrester JS, Kim CJ, Berglund H, Siegel RJ. Transcutaneous ultrasound augments lysis of arterial thrombi in vivo. Circulation. 1996 Aug 15;94 (4):775-8. doi: 10.1161/01.cir.94.4.775. PMID:8772701.
53. Siegel RJ, Atar S, Fishbein MC, Brasch AV, Peterson TM, Nagai T, Pal D, Nishioka T, Chae JS, Birnbaum Y, Zanelli C, Luo H. Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction. Circulation. 2000 May 2;101(17):2026-9. doi: 10.1161/01.cir.101.17.2026. PMID: 10790341.
54. Cohen M et al. Transcutaneous ultrasound-facilitated coronary thrombolysis during acute myocardial infarction. Am J Cardiol. 2003 Aug 15; 92(4):454-7. doi: 10.1016/s0002-9149(03)00666-0.
55. Hudson M, Greenbaum A, Brenton L, Gibson CM, Siegel R, Reeves LR, Sala MF, McKendall G, Bluguermann J, Echt D, Ohman EM, Weaver WD. Adjunctive transcutaneous ultrasound with thrombolysis: results of the PLUS (Perfusion by ThromboLytic and UltraSound) trial. JACC Cardiovasc Interv. 2010;3(3):352–359. doi: 10.1016/j.jcin.200 9.11.020
56. Child SZ, Hartman CL, Schery LA, Carstensen EL. Lung damage from exposure to pulsed ultrasound. Ultrasound Med Biol. 1990;16:817–25.
57. Miller DL, Dou C, Dong Z. Lung ultrasound induction of pulmonary capillary hemorrhage in neonatal swine. Ultrasound Med Biol. 2022;48: 2276–2291.
58. Miller DL. Induction of pulmonary hemorrhage in rats during diagnostic ultrasound. Ultrasound Med Biol 2012; 38:1476–1482.
59. Siegel RJ, Suchkova VN, Miyamoto T, Luo H, Baggs RB, Neuman Y, Horzewski M, Suorsa V, Kobal S, Thompson T, Echt D, Francis CW. Ultrasound energy improves myocardial perfusion in the presence of coronary occlusion. J Am Coll Cardiol. 2004 Oct 6;44(7):1454-8. doi: 10.1016/j.jacc.200 4.06.062. PMID: 15464327.
60. Xie F, Lof J, Matsunaga T, Zutshi R, Porter TR. Diagnostic ultrasound combined with glycoprotein IIb/IIIa-targeted microbubbles improves microvascular recovery after acute coronary thrombotic occlusions. Circulation 2009;119:1378-1385.
61. Qiu S et al. Sono-assisted-thrombolysis by three-dimensional diagnostic ultrasound improves epicardial recanalization and microvascular perfusion in acute myocardial infarction. Biostudies-literature, V1; 2022.
https://www.ebi.ac.uk/biostudies/studies/S-EPMC9511427.
62. Li H, Lu Y, Sun Y, Chen G, Wang J, Wang S, Huang C, Zhong L, Si X, Liao W, Liao Y, Cao S, Bin J. Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No-Reflow in Canine Models by Sonothrombolysis. Crit Care Med. 2018 Sep;46(9):e912-e920. doi: 10.1097/CCM.000 0000000003255. PMID: 29965834; PMCID: PMC6 110622.
63. Slikkerveer J., Kleijn S.A., Appelman Y., et al. Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: pilot of the sonolysis study. Ultrasound Med Biol 2012;38:247-252.
64. Mathias, W, Tsutsui, J, Tavares, B. et al. Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention. JACC. 2019 Jun, 73 (22) 2832–2842.
https://doi.org/10.1016/j.jacc.2019.03.006
65. Jeyaprakash P, Pathan F, Ozawa K, Robledo K, Shah K, Morton R, Yu C, Madronio C, Hallani H, Loh H, Boyle A, Ford T, Porter T, Negishi K.Trial Designs Restoring microvascular circulation with diagnostic ultrasound and contrast agent: rationale and design of the REDUCE trial. American Heart Journal, Volume 275, September 2024, Pages 163-172
66. Bainey KR, Abulhamayel A, Aziz A, Becher H. Sonothrombolysis Augments Reperfusion in ST-Elevation Myocardial Infarction With Primary Percutaneous Coronary Intervention: Insights From the SONOSTEMI Study. CJC Open. 2022 Mar 12;4(7):644-646. doi: 10.1016/j.cjco.2022.03.004. PMID: 35865027; PMCID: PMC9294977.
67. El Kadi S, van de Veerdonk MC, Spoormans EM, Verouden NJW, Li S, Xie F, Azevedo LF, Mathias W Jr, van Rossum AC, Porter TR, Kamp O. Sonothrombolysis in Patients With ST-Elevation Myocardial Infarction With Electrocardiographic No-Reflow After Percutaneous Coronary Intervention: A Randomized Controlled Trial. J Am Soc Echocardiogr. 2024 Oct; 37(10):981-992. doi: 10.1016/j.echo.2024.06.018. Epub 2024 Jul 6. PMID: 38972613.
68. Al Saikhan L, Alshami AM. Prevalence and Burden of Musculoskeletal Pain among Cardiac Sonographers in Eastern Province of Saudi Arabia: A Cross-Sectional Study. J Clin Med. 2024 May 29;13(11):3184. doi: 10.3390/jcm13113184. PMID: 38892895; PMCID: PMC11172581.
69. Brush K, Chaudry H, Berry N, Young M, Devries J, Friend L, Kane J and Rothstein E. First-in-Human Experience of Targeted Coronary Sonothrombolysis: A Novel Approach for Management of Refractory Coronary Thrombus. JACC: Case Reports, Volume 30, Number 20, 23 July 2025.
70. Hoffmann A: Low Frequency Vibration Assisted Blood Perfusion Emergency System. US Patent No. 7,517,328. 2004.
71. Hoffmann A: Vibratory with a plurality of contact nodes for treatment of myocardial ischemia. US Patent No. 8,079,968. 2008.
72. Khosrow-khavar F, Marzencki M, Tavakolian K, Kajbafzadeh B, Kaminska B, Menon C: Diastolic Timed Vibrator: Applying Direct Vibration in Diastole to Patients with Acute Coronary Ischemia during the Pre-hospitalization Phase. Autonomous and Intelligent Systems. AIS 2011. Lecture Notes in Computer Science, Vol 6752, 355-56 doi.org/10.10 07/978-3-642-21538-4_35
73. Kajbafzadeh B, Marzencki M, Alavi N, Khosrow-Hhavar F, Menon C, Kaminska B: Preferred patterns of diastolic timed vibrations for pre-hospitalization treatment of acute coronary ischemia. Conf Proc IEEE Med Biol Soc 2011, 2011:2480–2483.
74. Hoffmann A, Gill H: A study to determine chest wall vibratory attachment interface locations for a low frequency sonic vibrator in treatment of acute coronary thrombosis. J Thromb Thrombolysis Aug. 2011, 32(2):167– 176. doi:10.1007/s11239-011-0589-2
75. Gill H, Hoffmann A: The Timing of Onset of Mechanical Systole and Diastole in Reference to the QRS-T Complex: a Study to Determine Performance Criteria for a Non-Invasive Diastolic Timed Vibration Massage System in Treatment of Potentially Unstable Cardiac Disorders.” Cardiovascular Engineering 10 (2010): 235-245.
76. Bartel, L.; Mosabbir, A. Possible Mechanisms for the Effects of Sound Vibration on Human Health. Healthcare 2021, 9, 597.
77. Nowak-Lis A, Nowak Z, Gabrys T, Szmatlan-Gabrys U, Batalik L, Knappova V. The Use of Vibration Training in Men after Myocardial Infarction. Int J Environ Res Public Health. 2022 Mar 11;19(6): 3326. doi: 10.3390/ijerph19063326. PMID: 35329 010; PMCID: PMC8951545.
78. Coronary Growth? A Literature Review and Initial Experience in View to Pilot Testing. Advances in Tissue Engineering & Regenerative Medicine: Open Access. 1. 10.15406/atroa.2016.01.00007.
79. Lupowitz L. Vibration Therapy - A Clinical Commentary. Int J Sports Phys Ther. 2022 Aug 1;17(6):984-987. doi: 10.26603/001c.36964. PMID: 36237646; PMCID: PMC9528696.
80. Yohannes FG, Hoffmann AK: Non-invasive low frequency vibration as a potential adjunctive treatment for heart attack and stroke. An in-vitro flow model. J Thromb Thrombolysis 2008, 25(3): 251–258. doi:10.1007? s11239-007-0054-4
81. Hoffmann A, Gill H: Externally Applied Vibration at 50 Hz Facilitates Dissolution of Blood Clots In-Vitro. Am. J. Biomed. Sci. 2012, 4(4), 274-284; doi: 10.5099/aj120400274
82. Hoffmann A, Gill H: Diastolic timed Vibro-Percussion at 50 Hz delivered across a chest wall-sized meat barrier enhances clot dissolution and remotely administered Streptokinase effectiveness in an in-vitro model of acute coronary thrombosis. Thrombosis J 10, 23 (2012). https://doi.org/10.1186/1477-9560-10-23
83. Marzencki M, Kajbafzadeh B, Khosrow-khavar F, Tavakolian K, Soleimani-Nouri M, Hamburger J, Kaminska B, Menon C: Low frequency mechanical actuation accelerates reperfusion in-vitro. Biomed Eng Online. 2013;12: 21. Published online doi: 10.1186/1475-925X-12-121
84. Vermarien H: Phonocardiography. Wiley Online Library. Encyclopedia of Medical Devices and Instrumentation. First published 14 April 2006. https://doi.org/10.1002/0471732877.emd203
85. Thomas J, Cook D, Brooks D: Chest physical therapy management of patients with cystic fibrosis: a meta-analysis. Am J Respir Crit Care Med 1995, 151:846–850.
86. Koiwa Y, Honda H, Takagi T, Kikuchi J, Hoshi N, Takishima T: Modification of human left ventricular relaxation by small-amplitude, phase–controlled mechanical vibration on the chest wall. Circulation 1997, 95:156–162. doi:10.1161/01 CIR.95.1.156
87. Takehiko Takagi, MD; Yoshiro Koiwa, MD; Jun-ichi Kikuchi, MD; Hideyuki Honda, MD; Nobuo Hoshi, MD; James P. Butler, PhD; and Tamotsu Takishima, MDKoiwa et. al. Diastolic Vibration Improves Systolic Function in Cases of Incomplete Relaxation. (1992) Circulation Vol 86 No. 6 pp 1955 - 1964.
88. Koiwa Y, Honda H, Hoshi N, Naya T, Kamada E: The effect of diastolic vibration on the coronary flow rate in the canine heart with ischemia. J Cardiovasc Diagn Procedures 1994, 12:110. Abstract (FRI – POS 05).
89. Koiwa Y, et al: Precordial or epicardial input of phase-controlled minute vibration: effect on the coronary flow rate in regional ischemia. In New Horizons for Failing Heart Syndrome. Edited by Sasayama S. Tokyo; New York: Springer; 1996:117–130.
90. Naya T, Koiwa Y, Honda H, et al: Diastolic vibration from the precordium increases coronary blood flow in humans. J Cardiovasc Diagn Procedures 1994, 12:110. Abstract (FRI – POS07).
91. Effects of Diastolic Vibration on Coronary Circulation, Japanese Journal of Medicine, Vol 32, (1994), Issue 3, pg. 180 - 187. https://doi.org/10.11239/jsmbe1963.32.180
92. Takagi T, Koiwa Y, Kikuchi J, et al: Diastolic vibration improves systolic function in cases of incomplete relaxation. Circulation 1992, 86:1955–1964.
93. Koiwa Y, Takagi T, Kikuchi H, Honda H, Hoshi N, Takishima T: The improvement of systolic function of depressed left ventricle by external vibration at diastole. Tohoku J Exp Med 1989, 159:169–170
94. Farber JJ, Purvis JH: Conduction of cardiovascular sound along arteries. Circ Res 1963, 12:308–316.
95. Koiwa Y, Hashiguchi R, Ohyama T, et al: Measurement of instantaneous viscoelastic properties by impedance-frequency curve of the ventricle. Am J Physiol 1986, 250:H672–H684.
96. Hashiguchi R, Koiwa Y, Ohyama T, et al: Dependence of instantaneous transfer function on regional ischemic myocardial volume. Circ Res 1988, 63:1003–1011. doi:10.1161/01.RES.63.6.1003.
97. Smith D, Ishimitsu T, Craige E: Mechanical vibration transmission characteristics of the left ventricle implication with regard to auscultation and phonocardiography. J Am Coll Cordiol 1984, 4(3):517–521. doi:10.1016/S0736-1097(84)800959.
98. A Uryash H Gill, A Hoffmann. Can Upper Torso Vibro Acoustic Stimulation Treat No Reflow following STEMI Directed PPCI?. Rationale and Literature Review. 2016; 24: 36-38. 8.
99. A Uryash, H Gill, A Hoffmann. Upper Torso Vibroacoustic Stimulation for Treatment of No-Reflow Following STEMIDirected PPCI: A Device and Pilot Study Protocol. Shake, Rattle, and Rock n’-Reflow! Cath Lab Digest. 2016; 24: 2-5.
100. Roule, V., Ardouin, P., Blanchart, K. et al. Prehospital fibrinolysis versus primary percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Crit Care 20, 359 (2016). https://doi.org/10.1186/s13054-016-1530-z
101. Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) Investigators: Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 2006; 367: 569.
102. Hoffmann, A K. Chest Strikes, Back Slams, and Coughing to Promote Early Reflow in STEMI. Cardiol Cardiovasc Res. 2025;3(3):1-13.
103. Hoffmann, A K. Chest Strikes to treat STEMI? Exploring the Platinum Seconds of Reperfusion. Cardiol Vasc Res. 2025; 9(2): 1-7.