Valvosoft: fresh hope to AS patients unfit for valve replacement.

Calcific aortic stenosis (CAS) is currently the most common heart valve disease and to date only surgical or transcatheter aortic valve replacement are the available treatments. But, 16% of patients with symptomatic severe CAS are rejected by local heart teams for both these procedures. Valvosoft (Cardiawave) device, based on non-invasive ultrasound therapy (NIUT), has shown positive results for this specific population in a first-in-human study published recently in Circulation Journal.

The mechanism of action of NIUT consists of generating microscopic cavitation bubbles with short, high-pressure ultrasound pulses focused on the aortic valve (AV). As cavitation bubbles collapse, they produce shock waves inducing mechanical softening of the targeted calcified valve leaflet. The therapeutic dose was estimated as the mean acoustic focal energy (J/mm2) that integrates focal intensity over procedure duration.

10 patients (mean age, 84.1±6.5 years; 50% women) had severe CAS (mean AV area, 0.61±0.18 cm2; mean pressure gradient, 37.5±10.5 mmHg) and presented with severe comorbidities. NIUT could be delivered on the AV transthoracically in all patients using the real-time echo guiding of the device. Mean ultrasound delivery time was 52 minutes (range, 37–60 minutes), and mean acoustic focal energy delivered on the AV was 221±87 J/mm2.

7 patients were treated in a hybrid operating room and 3 in a catheterization laboratory. Events such as arrhythmia and chest wall discomfort from transducer pressure were managed with sedation or analgesia combined with short pauses in ultrasound application. Six patients were treated without general anesthesia, 4 of them without sedation. No deaths, myocardial infarctions, strokes, or transient ischemic attacks were reported at the 1-month follow-up.

Clinical and echocardiographic evaluation was performed by an independent core laboratory. No significant difference between baseline and follow-up at 1 month was observed in the Mini-Mental State Examination score, suggesting that the cognitive function was not impaired. No changes in left ventricular function and volumes were observed. For the overall population, a nonsignificant increase in AV area of 16.4% (0.61 cm2 versus 0.71 cm2 ; P=0.112) and a nonsignificant decrease in mean pressure gradient of 12.5% (37.5 mmHg versus 32.8 mmHg; P=0.191) were observed.

But there was wide variability in treatment response. Six patients were with an increase in AV area of 27.6% (P=0.03), associated with a decrease in mean pressure gradient of 23.5%). The duration of therapy was significantly longer in the responder group than in the nonresponder group (56.8±3.7 minutes versus 44.4±7.0 minutes; P180 J/mm2) Post hoc exploratory analysis attempting to identify factors potentially associated with treatment response suggests that a minimum treatment duration and focal energy may be needed to obtain a clinical effect.

Overall, current clinical data show that NIUT was feasible in patients with severe CAS. Further studies with optimized treatment and longer follow-up are required to evaluate the safety, performance, and durability of this new technique and to determine the population benefiting most.

In the near future, this therapy might be used for other indications, such as to improve patients' condition and prepare them for TAVR (bridge to TAVR) and for less sick patients (severe asymptomatic and moderate aortic stenosis) to slow down the progression of their disease and delay the moment they need replacement of their valves.

This therapy can be done ambulatory and can be very cost-effective. In addition, as it is non-invasive, it most probably can be repeated to further improve or maintain its effect.

Source: Circulation journal: https://doi.org/10.1161/CIRCULATIONAHA.120.050672