PINCH trial: First blinded RCT finds preoperative forearm exercises increase target vein diameter

In a recent research letter published in the European Journal of Vascular and Endovascu­lar Surgery, a group of researchers—led by Koen van der Bogt (Haaglanden Medical Centre [HMC], The Hague, The Netherlands)—discuss the PINCH trial and its hypothesis that preoperative exercise may result in larger blood vessel diameters at the time of arterio­venous fistula (AVF) creation, aiding in the surgical formation of forearm AVFs. According to this letter, the PINCH trial was able to show a moderate increase in cephalic vein diame­ter thanks to preoperative arm exercises for six weeks before surgery, with an additional improvement for patients that had an increased pinching force in the same timeframe.

According to figures quoted by van der Bogt et al, rates of radiocephalic fistula (RCF) matu­ration failure are as high as 30–60%, imply­ing that methods to improve maturation are needed. The current recommendations given by international guidelines to aid in improving RCF matu­ration are that regular forearm exercise in the first months after AVF creation that, based on small, non-randomised studies, is shown to aid in fistula maturation. However, the PINCH trial shows that doing these exercises preoperatively may in fact yield better results for maturation, due to the increased diameter of blood vessels.

The design of the PINCH trial—which the authors aver has been previously approved by the medical ethics board—was intended to detect a 0.58mm improvement in mean venous diameter in the treatment group (equalling an estimated 66% increase in blood flow) with a power of 80% and an alpha level of 5%. To do so, the researchers deter­mined that they would need 16 patients per group. Due to this, they enrolled 24 patients (to allow for any drop-outs). Predialysis patients or those on haemo­dialysis through a contralateral central venous catheter scheduled for creation of an AVF were eligible. A standard preoperative arte­rial and venous duplex was performed in both arms by blinded vascular laboratory technicians.

Patients that were randomly assigned to the intervention (PINCH) group received a real time moni­tored handgrip training device, which was paired to a game on a tablet device intended to aid in the exercises. At baseline, patients received instructions and a training schedule containing exercises for 10 minutes, three times daily for a total of six weeks. Van der Bogt et al also state that patients attended weekly supervised physio­therapy sessions, allowing for training to be adjusted based on maximum pinch force for each individual. After six weeks, duplex ultrasound was repeated, and pinch force was assessed. AVF surgery was then performed six–eight weeks after the forearm training began, with follow-up visits that included a duplex ultrasound planned for six weeks post AVF creation. The primary endpoint was increase in cephalic vein diameter after six weeks of forearm exercise.

Whilst 66 patients were eligible, only 48 of the patients recruited gave consent and were randomised. Nine patients withdrew from the study after inclusion, but before starting the train­ing schedule (seven in the intervention and two in the control group). The authors highlighted that patient characteristics showed little to no signif­icant differences between the two groups.

Initially, the baseline vascular diame­ter measurements were found to be larger in the control group, but at six weeks, patients that had been assigned to the intervention group showed a greater increase in cephalic vein diameter at elbow level. The study also found that a subgroup of PINCH patients with increased pinching force showed significantly greater increases in the vascular diameter of the cephalic vein at the elbow when evaluated with a tourniquet. As well as this, the authors state that there was an increase in compliance (no tourniquet versus tourniquet) of the cephalic vein at the elbow. There were no differences in the diameter of the cephalic vein at wrist level.

Van der Bogt and the co-authors of this letter state that the PINCH study is “the first blinded randomised controlled trial (RCT) investigating the impact of preoperative forearm exercise on target vein diameter, using directly and remotely supervised exercises”. They argue it shows that responsiveness to forearm exercise relies on adherence to the training programme, with, as they phrase it, a “moderate positive effect on cephalic vein diameter at the elbow and on cephalic vein compliance”.

Preoperative cephalic vein diameter, accord­ing to the authors, is a key predictor of AVF matu­ration. Venous distensibility, resembling vascular compliance, has also shown a significant correla­tion with AVF maturation. In this study, increased cephalic vein diameter and compliance were clinically significant, potentially improving AVF outcomes, which has to be evaluated in future studies. The current study was not powered to assess AVF maturation directly, one of the limita­tions of this small RCT, the authors state.

One thing that the authors did draw to the readers’ attention was the physicalfav study, the results of which were published in 2021 in the Journal of Nephrology. This study, which they state is the only other RCT on six to eight weeks of unsupervised upper and forearm exercises before AVF creation—although not a blinded study—reported increased venous and arterial diameters, promoting the creation of more fore­arm AVFs. They do add that larger baseline vascu­lar dimensions and physical capacity, compared with patients that participated in the PINCH trial, could explain the more favourable reported outcomes that Ines Aragoncillo Sauco (Gregorio Marañón General University Hospital, Madrid, Spain) et al experienced during the physicalfav trial. Van der Bogt et al state that the results of this earlier trial may suggest that preoperative forearm exercises may be particularly benefi­cial in patients with adequate baseline strength.

In their conclusion, the authors of the research letter state that “a moderate effect on vasodila­tion is to be expected from well executed fore­arm exercises in patients with adequate strength at baseline”. They add, however, that there is still more work and research that is needed in this area. The ideal composition of a training programme, which they say “will be a trade-off between intensity and burden”, should be stud­ied and further established.