Adding Drug-Coated Balloon Angioplasty to Stenting Reduces Pulmonary Vein Restenosis

In patients with pulmonary vein stenosis (PVS) or pulmonary vein total occlusion (PVTO) due to pulmonary vein isolation, drug-coated balloon (DCB) angioplasty prior to stenting reduces risk of restenosis and target lesion revascularization. So indicates a retrospective study by Cleveland Clinical investigators published in JACC Clinical Electrophysiology (2024;10(8):1840-1847) examining Cleveland Clinic’s experience with the novel technique.

“This is the first study demonstrating the efficacy and safety of drug-coated balloon angioplasty plus stenting for pulmonary vein stenosis and total occlusion,” says senior author Joanna Ghobrial, MD, MSc, Medical and Interventional Director of Cleveland Clinic’s Adult Congenital Heart Disease Center. “Our data support a high efficacy rate for stent patency in veins that were occluded, with reduced rates of restenosis or reintervention during follow-up.”

Aiming to fill a gap in therapy

PVS is a rare condition associated with high morbidity, and it can occur secondary to radiofrequency pulmonary vein isolation (PVI). Incidence of symptomatic PVS due to PVI has fallen in recent years as approaches to PVI have improved, though other causes of PVS remain. However, PVS can be missed because symptoms may be subtle or lacking, which places patients at risk for pulmonary hypertension and right-sided heart failure.

Treatment for PVS or PVTO (the more severe presentation, with 100% occlusion) typically is with angioplasty or stenting. Short-term patency is good with angioplasty, but more than 50% of patients experience restenosis. “Bare metal stenting, preferably to a diameter of at least 7 mm, is associated with lower restenosis and reintervention rates than balloon angioplasty alone,” says Dr. Ghobrial. “Even with stenting, however, the rate of restenosis and reintervention remains high, especially in the first six to 12 months, particularly in patients with pulmonary vein total occlusion.”

In theory, drug-eluting stents should improve outcomes for patients with PVS or PVTO, but they are not available in diameters > 5 mm, whereas the most enduring patency has been documented with stents ≥7 mm. “Given that the proposed mechanism of pulmonary vein stenosis due to pulmonary vein isolation involves intimal proliferation, combined with the availability of drug-eluting stents in only smaller diameters, we hypothesized that drug-coated balloons could fill a crucial gap in therapy, particularly for patients at high risk of restenosis and target lesion revascularization,” Dr. Ghobrial explains.

Mining data for stent insights

Data were analyzed for patients treated at Cleveland Clinic for PVS or PVTO. Some patients were asymptomatic, but all had evidence of stenosis or occlusion on imaging with ECG-gated CT angiography with contrast.

The DCB group comprised 26 patients who received angioplasty and stenting between January 2018 and January 2021. The control group included 58 patients who underwent stenting alone between December 2012 and December 2016. Treated veins totaled 33 in the DCB group and 89 in the control group.

“Although there was a difference in treatment period between the two groups, the procedural techniques for pulmonary vein recanalization and stenting were not markedly different,” Dr. Ghobrial notes.

Before all interventions, a multidisciplinary discussion was held. The DCB group underwent DCB angioplasty. Stent choice was based on reference vessel diameter (drug-eluting stent for diameters ≤5.0 mm, bare metal stent for diameters ≥6.0 mm). Bare metal stents predominated, with use in 88% of the DCB group and 97.7% of the control group.

All patients received aspirin or clopidogrel plus a direct oral anticoagulant or warfarin. If triple therapy was prescribed, the duration was limited to one month.

Risk of restenosis and target lesion revascularization was assessed with multivariable Andersen-Gill regression analysis. Only PVS/PVTO due to PVI was included.

Findings and clinical implications

Unadjusted rates of restenosis and target lesion revascularization were significantly lower in the DCB group than in controls (14.3% vs. 26%, respectively, for restenosis, and 10.7% vs. 34.2%, respectively, for target lesion revascularization). A similar outcome was seen after adjustment for age, gender, antiplatelet and anticoagulation therapy, total occlusion rate, and stent size (hazard ratio [HR] = 0.003; 95% CI, 0.00009-0.118; P = .002).

Significantly lower risks of restenosis and target lesion revascularization were associated with larger stent size, irrespective of treatment group (HR = 0.563; 95% CI, 0.353-0.897; P = .016).

Only 24.7% of patients in the control group remained on at least one antiplatelet drug for six months or more, compared with all patients in the DCB group. After adjustment for antiplatelet therapy, the control group still had higher rates of restenosis and target lesion revascularization than the DCB recipients.

“The DCB group was more likely to have pulmonary vein total occlusion and smaller vessels and stent diameter, yet they had lower rates of restenosis as documented on CT and lower rates of reintervention,” Dr. Ghobrial observes.

The investigators note that their findings are limited by shorter follow-up in the DCB group, which was a mean/median of approximately one year, versus nearly three years in the control group. They point out, however, that most stent failures occur within the first year. They ascribe the high loss to follow-up over the long term to the large proportion of patients referred from outside centers.

“Prospective and randomized clinical trials with long-term follow-up evaluating drug-coated balloons for pulmonary vein stenosis and occlusion are needed to reach definitive conclusions,” Dr. Ghobrial says. “However, our data show that performing DCB angioplasty before stenting is effective and safe and may reduce the risk of restenosis compared with standard of care.”

“In the current era, DCB is an important first treatment for patients with pulmonary vein stenosis,” adds co-author Samir Kapadia, MD, Chair of Cardiovascular Medicine at Cleveland Clinic. “DCB followed by stenting, as will be required in the future, is a better strategy to prevent recurrent restenosis and potentially place larger-caliber stents.”