Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial.

BACKGROUND AND AIMS: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium. METHODS: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled. Patients were randomly assigned to undergo direct cardiac SWT or sham treatment in addition to coronary bypass surgery. The primary efficacy endpoint was the improvement in LVEF measured by cardiac magnetic resonance imaging from baseline to 360 days. RESULTS: Overall, 63 patients were randomized, out of which 30 patients of the SWT group and 28 patients of the Sham group attained 1-year follow-up of the primary endpoint. Greater improvement in LVEF was observed in the SWT group (Δ from baseline to 360 days: SWT 11.3%, SD 8.8; Sham 6.3%, SD 7.4, P = .0146). Secondary endpoints included the 6-minute walking test, where patients randomized in the SWT group showed a greater Δ from baseline to 360 days (127.5 m, SD 110.6) than patients in the Sham group (43.6 m, SD 172.1) (P = .028) and Minnesota Living with Heart Failure Questionnaire score on day 360, which was 11.0 points (SD 19.1) for the SWT group and 17.3 points (SD 15.1) for the Sham group (P = .15). Two patients in the treatment group died for non-device-related reasons. CONCLUSIONS: In conclusion, the CAST-HF trial indicates that direct cardiac SWT, in addition to coronary bypass surgery improves LVEF and physical capacity in patients with ischaemic heart failure.

Combined Electromagnetic and Electrohydraulic Focused ESWT and EMTT for Delayed Calcaneal Union in an Adolescent Parkour Athlete - A Case Report.

This case report describes a novel and unique combination of both electromagnetic and electrohydraulic focused extracorporeal shockwave therapy (ESWT) and extracorporeal magnetotransduction therapy (EMTT) for accelerated healing in a calcaneus epiphyseal fracture with delayed healing in an adolescent Parkour athlete. After a 2.5m jump, the 14-year-old experienced significant heel pain, however avoided telling his parents. After eight weeks, the initial imaging using ultra low dose weight-bearing cone beam CT (WBCT) revealed a calcaneus non-union situation adjacent to the open calcaneal physis. To improve and accelerate bony healing substantially, we chose to apply both combined focused electromagnetic (Storz Ultra, Storz Medical AG, Tägerwillen, CH) and focused electrohydraulic (MTS, Konstanz, Germany) ESWT in a fractioned fashion plus EMTT (Storz Magnetolith, Tägerwillen, CH) in five consecutive weekly sessions while allowing the patient to fully weight bear. The follow-up WBCT after six weeks revealed a near to total healing of the delayed union and being pain-free. Notably, combination therapy with focused ESWT and EMTT did not result in early closure of the calcaneal epiphysis. We conclude that combined focused electromagnetic and electrohydraulic ESWT and EMTT facilitate bony healing in adolescent calcaneal apophyseal fractures without any adverse effects on the open physis. Evidence level IV (case report).

Safe and Effective Treatment of Compromised Clavicle Fracture of the Medial and Lateral Third Using Focused Shockwaves.

A delay or failure to heal is the most common possible complication in clavicle fractures, especially in cases primarily treated conservatively. As the current standard therapy, surgical revision achieves good healing results, but is associated with potential surgery-related complications. Shockwave therapy as a non-invasive therapy shows similar reasonable consolidation rates in the non-union of different localizations, but avoids complications. Compromised clavicle fractures in the middle and lateral third treated with focused high-energy shockwave therapy were compared with those treated with surgical revision (ORIF). In addition, a three-dimensional computer simulation for evaluating the pressure distribution during shockwave application accompanied the clinical study. A comparable healing rate in bony consolidation was achieved in both groups. Significantly fewer complications, however, occurred in the shockwave group. The simulations showed safe application in this instance, particularly in avoiding lung tissue affection. When applied correctly, shockwaves represent a safe and promising therapy option for compromised clavicle fractures in the middle and lateral third.

The effect of extracorporeal shock wave therapy in acute traumatic spinal cord injury on motor and sensory function within 6 months post-injury: a study protocol for a two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled clinical trial.

BACKGROUND: The pathological mechanism in acute spinal cord injury (SCI) is dual sequential: the primary mechanical lesion and the secondary injury due to a cascade of biochemical and pathological changes initiated by the primary lesion. Therapeutic approaches have focused on modulating the mechanisms of secondary injury. Despite extensive efforts in the treatment of SCI, there is yet no causal, curative treatment approach available. Extracorporeal shock wave therapy (ESWT) has been successfully implemented in clinical use. Biological responses to therapeutic shock waves include altered metabolic activity of various cell types due to direct and indirect mechanotransduction leading to improved migration, proliferation, chemotaxis, modulation of the inflammatory response, angiogenesis, and neovascularization, thus inducing rather a regeneration than repair. The aim of this clinical study is to investigate the effect of ESWT in humans within the first 48 h after an acute traumatic SCI, with the objective to intervene in the secondary injury phase in order to reduce the extent of neuronal loss. METHODS: This two-arm three-stage adaptive, prospective, multi-center, randomized, blinded, placebo-controlled study has been initiated in July 2020, and a total of 82 patients with acute traumatic SCI will be recruited for the first stage in 15 participating hospitals as part of a two-armed three-stage adaptive trial design. The focused ESWT (energy flux density: 0.1-0.19 mJ/mm2, frequency: 2-5 Hz) is applied once at the level of the lesion, five segments above/below, and on the plantar surface of both feet within the first 48 h after trauma. The degree of improvement in motor and sensory function after 6 months post-injury is the primary endpoint of the study. Secondary endpoints include routine blood chemistry parameters, the degree of spasticity, the ability to walk, urological function, quality of life, and the independence in everyday life. DISCUSSION: The application of ESWT activates the nervous tissue regeneration involving a multitude of various biochemical and cellular events and leads to a decreased neuronal loss. ESWT might contribute to an improvement in the treatment of acute traumatic SCI in future clinical use. TRIAL REGISTRATION: ClinicalTrials.gov NCT04474106.

High-energy extracorporeal shockwave therapy in humeral delayed and non-unions.

INTRODUCTION: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions. MATERIALS AND METHODS: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT. RESULTS: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002). CONCLUSION: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions.

Antibody seroprevalence and rate of asymptomatic infections with SARS-CoV-2 in Austrian hospital personnel.

BACKGROUND: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening. METHOD: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days. RESULTS: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3. CONCLUSIONS: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.

The role of shockwaves in the enhancement of bone repair - from basic principles to clinical application.

Extracorporeal shockwave therapy is a treatment modality, originally introduced into the clinic as lithotripsie, which has also been successfully used in the last two decades in the non-invasive treatment of delayed or non-healing fractures. Initially, the mechanism of action was attributed to microfracture-induced repair, but intensive basic research has now shown that the shockwave generates its effect in tissue via mechanotransduction. Numerous signal transduction pathways have already been demonstrated, which in their entirety trigger an endogenous regeneration process via cell proliferation, migration and differentiation. Clinically, these shockwave-conveyed biological signals support healing of acute, delayed and non-union fractures. The attainable outcome is comparable to surgery but avoiding an open approach with associated potential complications. These advantageous properties with a clearly positive cost-benefit ratio make shockwave therapy a first line treatment in delayed and non-union fractures.

Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis.

BACKGROUND: Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed. OBJECTIVE: We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making. METHODS: We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury. RESULTS: The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking. CONCLUSIONS: Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

Effect of unfocused extracorporeal shockwave therapy on bone mineral content of twelve distal forearms of postmenopausal women: a clinical pilot study.

Extracorporeal shockwave therapy showed a pronounced effect on bone mass in previous animal studies. We showed in this pilot study that a single treatment with unfocused shockwave therapy in unselected patients does not show side effects. Although our study did not show any effect of shockwave on BMD, the limited sample size does not definitively exclude this and a study with 174 subjects per group would be needed to show an effect size of 0.3 with a power of 80%. PURPOSE: Unfocused extracorporeal shockwave therapy might stimulate bone formation to reduce the fracture risk. In this study, we assessed the safety of unfocused extracorporeal shockwave therapy and its effects on bone mass. METHODS: A clinical pilot study with twelve female patients free of bone disease undergoing elective surgery of the lower extremity or elective spinal surgery under general anesthesia received 3.000 electrohydraulic-generated unfocused extracorporeal shockwaves (energy flux density 0.3 mJ/mm2) to one distal forearm. The contralateral forearm served as a control. We examined the effect on bone mass with the use of repeated dual energy X-ray absorptiometry measurements and we measured patient discomfort around the therapy. RESULTS: No difference in bone mineral content and density was measured 6 and 12 weeks after therapy. shockwave therapy occasionally caused transient erythema or mild hematoma, but no discomfort in daily life or (late) adverse events. CONCLUSIONS: Unfocused extracorporeal shockwave therapy is a safe treatment, but no increase in bone mass on the forearm was found at 0.3 mJ/mm2 energy flux density. In this study, we were not able to demonstrate that a single treatment with unfocused shockwave therapy in unselected patients had any effect in terms of bone mineral density (BMD) or bone mineral content (BMC). A power analysis indicated that 174 patients per group are required to show an effect size of 0.3 with a power of 80%.

Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix.

Background Mechanical stimulation of acute ischemic myocardium by shock wave therapy ( SWT ) is known to improve cardiac function by induction of angiogenesis. However, SWT in chronic heart failure is poorly understood. We aimed to study whether mechanical stimulation upon SWT improves heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis and to dissect underlying mechanisms. Methods and Results SWT was applied in a mouse model of chronic myocardial ischemia. To study effects of SWT on postnatal vasculogenesis, wild-type mice received bone marrow transplantation from green fluorescence protein donor mice. Underlying mechanisms were elucidated in vitro in endothelial cells and murine aortic rings. Echocardiography and pressure/volume measurements revealed improved left ventricular ejection fraction, myocardial contractility, and diastolic function and decreased myocardial fibrosis after treatment. Concomitantly, numbers of capillaries and arterioles were increased. SWT resulted in enhanced expression of the chemoattractant stromal cell-derived factor 1 in ischemic myocardium and serum. Treatment induced recruitment of bone marrow-derived endothelial cells to the site of injury. In vitro, SWT resulted in endothelial cell proliferation, enhanced survival, and capillary sprouting. The effects were vascular endothelial growth factor receptor 2 and heparan sulfate proteoglycan dependent. Conclusions SWT positively affects heart function in chronic ischemic heart failure by induction of angiogenesis and postnatal vasculogenesis. SWT upregulated pivotal angiogenic and vasculogenic factors in the myocardium in vivo and induced proliferative and anti-apoptotic effects on endothelial cells in vitro. Mechanistically, these effects depend on vascular endothelial growth factor signaling and heparan sulfate proteoglycans. SWT is a promising treatment option for regeneration of ischemic myocardium.

Extracorporeal shockwave therapy (ESWT) ameliorates healing of tibial fracture non-union unresponsive to conventional therapy.

Tibial non-unions are common cause of demanding revision surgeries and are associated with a significant impact on patients' quality of life and health care costs. Extracorporeal shockwave therapy (ESWT) has been shown to improve osseous healing in vitro and in vivo. The main objective of present study was to evaluate the efficacy of ESWT in healing of tibial non-unions unresponsive to previous surgical and non-surgical measures. A retrospective multivariant analysis of a prospective open, single-centre, clinical trial of tibia non-union was conducted. 56 patients with 58 eligible fractures who met the FDA criteria were included. All patients received 3000-4000 impulses of electrohydraulic shockwaves at an energy flux density of 0.4mJ/mm(2) (-6dB). On average patients underwent 1.9 times (±1.3SD) surgical interventions prior to ESWT displaying the rather negatively selected cohort and its limited therapy responsiveness. In 88.5% of patients receiving ESWT complete bone healing was observed after six months irrespective of underlying pathology. The multivariant analysis showed that time of application is important for therapy success. Patients achieving healing received ESWT earlier: mean number of days between last surgical intervention and ESWT (healed - 355.1 days±167.4SD vs. not healed - 836.7 days±383.0SD; p<0.0001). ESWT proved to be a safe, effective and non-invasive treatment modality in tibial non-unions recalcitrant to standard therapies. The procedure is well tolerated, time-saving, lacking side effects, with potential to significantly decrease health care costs. Thus, in our view, ESWT should be considered the treatment of first choice in established tibial non-unions.

Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p < 0.001) and control (41 ± 4%, p = 0.012) groups. LVEF markedly improved in shock-wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd.

Effect of extracorporeal shockwave therapy (ESWT) on pulpal blood flow after orthodontic treatment: a randomized clinical trial.

OBJECTIVES: The effect of non-invasive extracorporeal shockwaves on pulpal blood flow in orthodontic patients who have undergone active treatment was investigated. MATERIALS AND METHODS: Seventy-two adult patients were enrolled in the clinical trial and allocated by block randomization to a treatment or a placebo group at a 1:1 ratio. The patients were required to be otherwise healthy. Blinding was performed for the subjects and the outcome assessor. The region of interest was the mandibular incisors and canines, which were vital, unrestored, and had experienced no trauma. The active treatment group received a single shockwave treatment with 1000 impulses at 0.19-0.23 mJ/mm(2) while the placebo group was treated with a deactivated shockwave applicator but acoustic sham. Pulpal blood flow was evaluated four times over a period of 6 months starting from the day of bracket removal, using a laser Doppler device. RESULTS: Thirty patients were evaluated in each group. Orthodontic patients who have undergone active treatment tend to have high levels of pulpal blood flow which decrease over a period of 6 months. Pulpal blood flow did not differ significantly over 6 months between the placebo and treatment group. Shockwave treatment was associated with no significant effect in respect of tooth type, age, sex, or mean blood pressure, and had no unintended pernicious effects. CONCLUSIONS: Extracorporeal shockwaves had no statistically significant effect on pulpal blood flow. Multiple applications of ESWT in a pathological setup may be needed in future studies to demonstrate significant differences. CLINICAL RELEVANCE: The absence of any adverse effects justifies further principal investigations of the use of shockwave treatment in the oral cavity.

Extracorporeal shockwave therapy (ESWT)--First choice treatment of fracture non-unions?

Fracture non-unions are still a challenging problem in orthopedics. The treatment of non-unions remains highly individualized, complex, and demanding. In most countries the surgical approach with debridement of the non-union gap, anatomical reduction and appropriate osteosynthesis along with autologous bone grafting is considered as the standard of care. One of the very first non-urologic applications of extracorporeal shockwave treatment (ESWT) concerned non-healing fractures. Since the early 1990ties the knowledge of the working mechanism has increased enormously. The purpose of this review article is to demonstrate by peer-reviewed literature in conjunction with our own experiences that ESWT can be an efficient, non-invasive, almost complication-free and cost effective alternative to surgical treatment of non-healing fractures.

Extracorporeal shockwave therapy in diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are among the most common foot disorders with ulceration, infection, and gangrene that may ultimately lead to lower extremity amputation. The goals of treatment include the control of diabetes and proper shoe wear. An effective therapy and appropriate foot care are important in wound healing in DFUs. Recently, extracorporeal shockwave therapy (ESWT) was reported to significantly promote and accelerate the healing of complex soft tissue wounds as compared to the standard methods of treatment in DFUs. ESWT showed positive results in short-term and long-term outcomes in diabetic patients suffering from foot ulcers. In this article, we review the clinical results of ESWT in DFUs.