Safety and efficacy of balloon angioplasty compared to stent-based-strategies with pulmonary vein stenosis: A systematic review and meta-analysis

Table 1 Main demographics of patients treated with either balloon angioplasty or stenting included in meta-analysis

Ref.	Patients (n)	Mean age (yr)	Males (%)	Frequency of clinical symptoms; Dyspnea (%)	Hemoptysis (%)	Asymptomatic (%)	Severe PVS treated (n)
Qureshi et al[19]	19	51 ± 13	NA	95	63	5	37
Prieto et al[7]	44	53 ± 11	70	88	23	7	68
Neumann et al[6]	12	58	70	77	8	17	15
Fender et al[20]	113	50	77	67	27	0	178
Cory et al[5]	30	Median age-6.4 m	50	NA	NA	NA	58
Schoene et al[15]	39	62.1 ± 9.0	60	79	26	NA	61
Kurita et al[9]	31	7 mo	65	NA	NA	NA	53
Suntharos et al[8]	199	55 ± 12	78	83	13	13	319

NA: Not available; PVS: Pulmonary vein stenosis.

Table 2 Clinical characteristics of patients treated with either balloon angioplasty or stenting included in meta-analysis

Ref.	Study type	Enrolment Period	Main inclusion criteria	Imaging after ablation	Mean time between PVI and clinical symptoms	Revascularization approach	Stent size	Acute angiographic success	Primary outcome at follow-up	Follow-up
Qureshi et al[19], 2003	Observational retrospective study	2000-2002	Severe PVS with clinical symptoms	CT-scans in symptomatic patients	4 mo	Stepwise	4-10 mm	NA	Freedom of reintervention	10 ± 9 mo
Prieto et al[7], 2008	Observational retrospective study	2000-2007	Severe PVS with clinical symptoms	CT-scans, lung perfusion scans in symptomatic patients	11.5 mo	Stepwise/primary stenting	8-10 mm	Residual stenosis ≤ 30%	Recurrence of symptoms requiring reintervention	25 ± 21 mo
Neumann et al[6], 2009	Observational prospective study	2003-2005	Severe PVS (> 70%) with clinical symptoms and/or significant perfusion defect	Surveillance imaging with MRI, lung perfusion scans, CT scans, TTE every 3 mo	NA	Stepwise (if rebound stenosis was observed after balloon dilatation)/primary stenting	8-12 mm	NA	Clinically symptomatic restenosis	48 mo
Fender et al[20], 2016	Observational prospective study	2000-2014	Severe PVS (> 75%) with clinical symptoms	Surveillance imaging with CT-scans at 3 mo + CT-scans and lung perfusion scans in symptomatic patients	4.0 ± 3.0 mo	Stepwise	6-10 mm + DES 4 mm	Residual stenosis < 20%	Clinically symptomatic restenosis	48 mo
Cory et al[5], 2017	Observational retrospective study	2005-2016	Catheter intervention for PVS for patients < 18 yr	NA	NA	Stepwise/primary stenting	Median-DES 4 mm, BMS 5 mm	NA	Mortality following transcatheter PV intervention	Median of 30.6 mo
Schoene et al[15], 2018	Observational retrospective study	2004-2017	Symptomatic PVS with > 70% in a single stenosis or > 60% in multiple ipsilateral stenosis	Initial screening process from 2004-2007- TEE 6-12 mo after PVI or when symptomatic, subsequent CT or MRI. Screening terminated in 2008, symptomatic patients underwent CT, MRI and/or PV angiography	10.2 ± 8.0 mo	Stepwise/primary stenting	Median stent- 7 mm × 20 mm, DES 5 mm	Residual stenosis < 10%-20%	Restenosis rate following transcatheter intervention	Median of 6 mo
Kurita et al[9], 2019	Observational retrospective study	2001-2017	PVS associated with total anomalous pulmonary venous connection and isolated congenital PVS	Combination of ultrasound, CT and angiography	Median 7 from birth	Stepwise/primary stenting-PCI/hybrid surgery	3-8 mm	NA	In-stent restenosis following stent placement using CT or angiography ≥ 50% higher stenosis of stent size	19 mo
Suntharos et al[8], 2019	Observational retrospective study	2000-2016	PVS after PVI undergoing PCI	CT-scan pulmonary vein protocol, quantitative lung perfusion scan	NA	Stepwise/primary stenting	3-16 mm	NA	Freedom of reinrevention	Median follow up-17 mo

CT: Computed tomography; DES: Drug-eluting stents; NA: Not available; PVI: Pulmonary vein isolation; PVS: Pulmonary vein stenosis; PV: Pulmonary vein; TEE: Transesophageal echocardiography; MRI: Magnetic resonance imaging; PCI: Percutaneous interventions.

Table 3 Follow up characteristics after revascularization

Ref.	Antiplatelet therapy	Imaging modalities	Restenosis definition
Qureshi et al[19], 2003	NR	CT-scans every 3 mo	PV narrowing > 70% of the original PV lumina
Prieto et al[7], 2008	NR	CT-scans, lung perfusion scans at 3-12-24 mo	NR
Neumann et al[8], 2009	ASA+Clopidogrel+Coumadin for 3 mo	CT-scans, lung perfusion scans every 3 mo	PV narrowing > 70%of the original PV lumina before PVI
Fender et al[20], 2016	Coumadin+Clopidogrel	CT-scans, lung perfusion scans at 3-12-24 mo	PV narrowing > 75% in the previously treated PV
Cory et al[5], 2017	NA	Angiography	Vein loss defined as PV atresia or PVs of uncertain status in deceased patients
Schoene et al[15], 2018	ASA 4 weeks+Clopidogrel 6 mo+Coumadin or DOACs	CT-scans, MR imaging	PV narrowing > 70% in the previously treated PV
Kurita et al[9], 2019	ASA, Ticlopidin, Warfarin	CT or angiography	In stent restenosis: ≥ 50% luminal narrowing
Suntharos et al[8], 2019	Anticoagulation followed by low-dose aspirin	CT-scans, lung perfusion scans, angiography based on intervention-3 mo, 6 mo, 1yr	Severe restenosis/concern for progression to total occlusion

ASA: Acetyl salicylic acid; CT: Computed tomography; NA: Not available; NR: Not reported; PV: Pulmonary vein; PVI: Pulmonary vein isolation.

Table 4 Summary of evidence

Outcomes	Anticipated absolute effectsa (95%CI)		Relative effect (95%CI)	No. of participants (studies)	Certainty of the evidence (GRADE)b
	Risk with PSI	Risk with PBA
Restenosis	251 per 1000	493 per 1000 (278 to 711)	OR 2.91 (1.15 to 7.37)	487 (8 observational studies)	⊕⊕⊕◯ MODERATEc
Procedure related complications	87 per 1000	82 per 1000 (21 to 264)	OR 0.94 (0.23 to 3.76)	191 (3 observational studies)	⊕⊕⊕◯ MODERATEc

^aThe risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95%CI).

^bGRADE Working Group grades of evidence: (1) High certainty: We are very confident that the true effect lies close to that of the estimate of the effect; (2) Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; (3) Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect; and (4) Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

^cRated down for imprecision as the 95% confidence interval overlaps with no effect and fails to exclude important benefit or important harm. PBA: Pulmonary vein balloon angioplasty; PSI: Pulmonary vein stent implantation.