Eisenmenger Syndrome: Background, Pathophysiology, Etiology

Shockwave Therapy Shows Benefit In Lower Limb Claudication

Extracorporeal shockwave therapy may be effective for intermittent lower limb claudication in peripheral artery disease (PAD) patients unable to engage in supervised exercise or who experienced little benefit from that standard first-line approach, a randomized trial suggested.

For the primary endpoint, patients who received nine sessions of the electrical impulses to the gastrocnemius muscle over a 3-week period had significantly greater improvements in physical function versus a sham therapy, as measured by the Physical Functioning domain of the 36-item Short-Form questionnaire (SF-36).

At 12 weeks, a 3.8-point (95% CI 0.0-7.7, P=0.03) greater estimated median difference on the 100-point scale emerged for patients assigned to the shockwave therapy, reported researchers led by Paris Cai, MBBCh, BAO, of Hull York Medical School in England.

Furthermore, the shockwave group had significantly greater improvements at this time point in pain-free walking distance (median 34.1 meters, 95% CI 11.4-56.8, P=0.004) and maximum walking distance (median 51.4 meters, 95% CI 10.7-86.5, P=0.01), according to findings of the single-center double-blind study published in JAMA Surgery.

Despite a post hoc analysis showing the primary endpoint lost significance when adjusted for baseline differences in coronary artery disease, the research team nevertheless concluded that extracorporeal shockwave therapy "appears to be a potential alternative to supervised exercise for patients with intermittent claudication that can improve patient choice and increase access and engagement with noninvasive treatment."

Intermittent claudication is a common manifestation of PAD that is characterized by muscle pain during activity due to a lack of blood flow, typically to the lower extremities.

Beyond smoking cessation and other forms of cardiovascular risk reduction, "supervised exercise is the recommended first-line treatment for intermittent claudication but is generally met with poor uptake and completion rates as low as 25% and 75% respectively," according to Cai and co-authors. As such, other noninvasive treatment options are needed, they said.

Extracorporeal shockwave therapy, which delivers short-wave acoustic pulses and may induce angiogenesis in treated tissue, has been used in a number of conditions such as musculoskeletal disorders and even myocardial ischemia. But evidence for its effectiveness in PAD has been limited outside of small studies, leading to the current first-of-its kind trial, which recruited patients from a tertiary center for vascular surgery.

"The aim of the intervention was not to eradicate claudication symptoms but to reduce them to enable patients to mobilize further," the researchers explained. "This means that there will be a continuing impact of intermittent claudication on quality of life."

No other secondary endpoints of the trial, which included ankle brachial pressure index and multiple other measures of quality of life, showed any between-group differences at 12 weeks, but some improvements favoring shockwave therapy were observed at earlier follow-ups.

In an invited commentary, Helen Potter, MD, and Linda Harris, MD, DFSVS, both of the Jacobs School of Medicine and Biomedical Sciences in Buffalo, New York, raised a host of issues with the findings, including whether efficacy will be sustained after stopping the shockwave therapy sessions and whether adherence might be as low as with exercise therapy, given that the study protocol involved nine sessions over a 3-week period. Of note, approximately two-thirds of eligible participants declined to participate in the trial.

They also questioned why the investigators included two very distinct groups in the trial: patients unable to receive supervised exercise and those still symptomatic following an exercise program.

"While these preliminary findings are intriguing, it is too early to call the results efficacious with assessment only out to 12 weeks," wrote Potter and Harris. "It will be extremely important to assess midterm and long-term benefits from intervention with extracorporeal shockwave therapy, need for repeat interventions, and whether repeat interventions will continue to be efficacious before endorsing this technology as appropriate for patients with lifestyle-limiting but not limb-threatening disease."

Cai and colleagues identified 389 eligible patients for the Shockwave Therapy in Lower Limb Intermittent Calf Claudication trial, of which 138 agreed to participate and were randomized 1:1 to nine sessions over 3 weeks of the intervention or sham treatment. Patients were excluded if they had active cancer or were on anticoagulants.

Intervention participants received 100 impulses of 0.1 mJ/mm/cm2 with the PiezoWave 2 shockwave system to the symptomatic calf muscle. The sham group underwent the same preparation for treatment, including the application of ultrasonography gel and having the transducer run over the affected area, but were given no impulses (a recording simulated delivery of the shockwaves).

At baseline, two-thirds of participants were male, the average age was 67 years, over 90% had a smoking history, and roughly 60% had hypertension. More patients in the sham arm had diabetes (36% vs 24% in the shockwave arm) and a history of coronary artery disease/ischemic heart disease (44% vs 32%). Overall, more than 90% had calf-exclusive claudication and about 10% had bilateral involvement.

Patients in the intervention and sham arms had median scores of 36.5 and 33, respectively, on the Physical Functioning domain of the SF-36 at the start of the trial. These increased to 41.3 and 34.6 at 12 weeks.

For the intervention arm, pain-free walking distance increased from 49 meters at baseline to 105.6 meters at 12 weeks, while maximum walking distance increased from 84.6 to 171.8 meters. In the control group, pain-free walking distance increased from 40 meters at baseline to 69.6 meters at 12 weeks, while maximum walking distance increased from 93.4 to 114.3 meters.

At 4 weeks, patients on the shockwave intervention had greater differences on the EuroQol 5-Dimension 3-Level survey (P=0.03), on the SF-36 General Health (P=0.004) and Vitality (P=0.03) domains, and on the SF-36 Physical Component Summary (PCS; P=0.02). An advantage on the PCS was seen at 8 weeks as well.

Along with the findings from the post hoc analysis and the single-center design, other limitations included the use of a constant load treadmill test to assess walking distances.

Correction: This story was updated to reflect that the sham arm had the higher rates of diabetes and coronary artery disease/ischemic heart disease at baseline.

Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow

Disclosures

No study funding was reported and the investigators had no disclosures.

Potter and Harris reported no conflicts of interest.

Primary Source

JAMA Surgery

Source Reference: Cai P, et al "Extracorporeal shockwave for intermittent claudication and quality of life: a randomized clinical trial" JAMA Surg 2024; DOI:10.1001/jamasurg.2024.0625.

Secondary Source

JAMA Surgery

Source Reference: Potter HA, Harris LM "Extracorporeal shockwave for claudication -- potential efficacy" JAMA Surg 2024; DOI:10.1001/jamasurg.2024.0626.

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Peripheral Artery Disease

An angiogram is a diagnostic imaging test that allows doctors to view blood vessels throughout the body and diagnose blockages, enlargements, clots, and malformations. An angiogram to study the arteries is called an arteriogram; one to study the veins is called a venogram. Before the test doctors inject a dye into the vessels to be imaged using a long, flexible, hollow tube called a catheter, which is usually introduced into the body through a needle puncture in the groin. The dye makes the blood vessels clearly visible on an x-ray image. Your doctor can combine an angiogram procedure with one of the minimally invasive procedures outlined below, which include balloon angioplasty, stenting, atherectomy, cryoplasty, or laser treatment.

Peripheral Artery Bypass

Content

Femoropopliteal (fem-pop) bypass surgery is used to bypass diseased blood vessels above or below the knee.

To bypass the narrowed or blocked blood vessel, blood is redirected through either a healthy blood vessel that has been transplanted or a man-made graft material. This vessel or graft is sewn above and below the diseased artery so that blood flows through the new vessel or graft.

Before you have surgery, the doctor will determine what type of material is best suited to bypass the blood vessel. Whenever possible, the surgeon will choose to use an existing piece of vein taken from the same leg. Man-made graft materials (such as polytetrafluoroethylene [PTFE] or Dacron) are more likely to become narrowed again, but they are still effective.

The section of vein or man-made blood vessel graft is sewn onto both the femoral and popliteal arteries so that blood can travel through the new graft vessel and around the narrowed or blocked area.

General anesthesia or an injection in the spine (epidural) is used for this surgery. General anesthesia will cause you to sleep through the procedure. An epidural prevents pain in the lower part of the body.

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