Adaptation of external counterpulsation based on individual shear rate therapy improves endothelial function and claudication distance in peripheral artery disease

Abstract

Peripheral artery disease (PAD) is the third leading cause of atherosclerotic cardiovascular morbidity and aff ects one in fi ve patients in primary care [1]. The overall number of PAD patients increased by 23.5 % over the last decade and has become a severe global health problem [2]. Nonsurgical and non-interventional treatment options for PAD patients comprise risk-factor modifi cation, pharmacological therapy and exercise. A supervised exercise program is a highly eff ective treatment option for PAD patients. However, intense training intervals elicit claudication and can be hindered by concomitant morbidities. Thus, novel therapies are needed.External counterpulsation is a non-invasive medical device, wherein pneumatic cuff s are wrapped around the lower limb and are triggered by an electrocardiogram. Upon diastole, the cuff s are infl ated, and at the onset of systole, they are defl ated again. During cuff infl ation, diastolic blood fl ow signifi cantly increases. This, in turn, leads to a profound increase in both intra-arterial shear rate and fl uid shear stress (FSS).Usually, external counterpulsation is applied with high pressures up to 250 or 300 mmHg, which is fre- Summary: Background: External counterpulsation therapy enhances blood fl ow and was shown to improve endothelial function and quality of life in coronary artery disease patients. However, high pressures of up to 300 mmHg may lead to malperfusion of the ischaemic limb. To improve the clinical outcome of patients with peripheral artery disease (PAD), we adjusted external counterpulsation and developed a novel non-invasive approach termed individual shear rate therapy (ISRT). Patients and methods: In the present study, 14 patients with a Fontaine stage IIb and femoral-popliteal PAD underwent 30 hours of ISRT over 5 weeks. For ISRT, individual treatment pressures that do not exceed 160 mmHg were assessed by Doppler fl ow parameters during counterpulsation (individual shear rate diagnosis) in order to enhance and maximise peripheral perfusion. The study aimed to enhance peripheral perfusion and evaluate the primary clinical endpoint endothelial function, as well as to perform preliminary analysis of the ankle brachial index (ABI) and walking distance. Results: Doppler fl ow measurements in the lower limb (ankle) validated that maximum blood fl ow velocity during systole and acceleration doubled during ISRT. Study results demonstrated that long-term ISRT signifi cantly increased fl ow-mediated dilation (FMD) in the brachial artery (0.13+/-0.09 mm to 0.38+/-0.05 mm; p < 0.05), while nitromediated dilation (0.36+/-0.10 mm to 0.45+/-0.08 mm) remained and common femoral artery FMD did not reach statistical signifi cance (0.38+/-0.08 mm to 0.67+/-0.19 mm; p<0.05). Initial claudication distance considerably improved for all patients after 30 hours of ISRT (92.6 +/-8.2 metres to 280+/-101.3 metres, p<0.05), just like the absolute claudication distance, which showed a more than 2.5-fold increase (167.8+/-18.1 metres to 446.7+/-133.3 metres; p<0.05). The...

Panta rhei: Everything flows - flow is everything Comment on Buschmann et al, p. 317 - 324

“…This autoregulation may underlie the previously observed inability to augment middle cerebral artery (MCA) mean fl ow velocity by full pressure (300 mmHg) EECP [14]. In contrast, a low pressure protocol applying only 75 mmHg led to an unexpected MCA mean fl ow velocity increase, which is in line with the observations by Buschmann et al [2] and demonstrates the profound need to 1) get mechanistic insight and 2) apply basic physiology. This can often achieve more than simply increasing the dose or, in this case, pressure.…”

“…However, personalised medicine is not limited to the prevention of adverse events, but aims to optimise the treatment eff ect individually. One of these rare examples is described in this issue of Vasa, where Buschmann and colleagues applied an individual calculation of the optimal shear rate for external counterpulsation therapy in peripheral artery disease patients [2]. While exercise undoubtedly remains one of the best and most eff ective treatments for coronary and peripheral artery disease, it is often not feasible due to comorbidities or other patient-specifi c factors.…”

Acute physical exercise and long‐term individual shear rate therapy increase telomerase activity in human peripheral blood mononuclear cells

“…For detailed population characteristics of the ISRT‐1 and ISRT‐2 trials, please consider Table as well as the publication of Buschmann et al . ().…”

“…ISRT specifically targets PAD and relies on a system, which was adapted from enhanced external counterpulsation (EECP), as earlier reported (Buschmann et al . ). EECP increases endovascular fluid shear stress by external compression of the lower extremities and thereby effectively enhances collateral growth and coronary vascular remodelling (Loh et al .…”

“…Recently, our group showed for the first time that long‐term ISRT is safe and effectively improves claudication symptoms, walking distance as well as the peripheral endothelial function in patients with PAD (Buschmann et al . ).…”