Pediatric Lung Transplantation for Pulmonary Vascular Diseases: Recent Advances and Challenges.

Pediatric lung transplantation for pulmonary vascular diseases has seen notable advancements and trends. Medical therapies, surgical options, and bridging techniques like extracorporeal membrane oxygenation and different forms of transplants have expanded treatment possibilities. Current challenges include ensuring patient adherence to post-transplant therapies, addressing complications like primary graft dysfunction and rejection, and conducting further research in less common conditions like pulmonary veno-occlusive disease and pulmonary vein stenosis. In this review article, the authors will explore the advancements, emerging trends, and persistent challenges in pediatric lung transplantation for pulmonary vascular diseases.

Interventions for Pulmonary Vein Stenosis.

Pulmonary vein stenosis (PVS) is a rare and unique disease of infants and young children. PVS is attended by high morbidity and mortality, and for many decades, effective therapy eluded the practitioner. However, in the most recent era, interventional techniques when employed in combination with systemic (primary) therapy have had a remarkable impact on outcomes in these at-risk children. Despite apparent complete relief of PVS in a discrete region of a pulmonary vein, stenosis reliably recurs and progresses. In this review, we discuss the current state-of-the-art interventional techniques, through the lens of our collective experiences and practices.

Pulmonary Vein Intervention for Severe Pulmonary Vein Stenosis After Atrial Fibrillation Ablation　- A Retrospective Cohort Study.

BACKGROUND: Pulmonary vein (PV) stenosis (PVS) is a serious complication of atrial fibrillation (AF) ablation. The objective of this study was to describe interventional treatments for PVS after AF ablation and long-term outcomes in Japanese patients.Methods and Results: This multicenter retrospective observational study enrolled 30 patients (26 [87%] male; median age 55 years) with 56 severe PVS lesions from 43 PV interventional procedures. Twenty-seven (90%) patients had symptomatic PVS and 19 (63%) had a history of a single AF ablation. Of the 56 lesions, 41 (73%) were de novo lesions and 15 (27%) were retreated. Thirty-three (59%) lesions were treated with bare metal stents, 14 (25%) were treated with plain balloons, and 9 (16%) were treated with drug-coated balloons. All lesions were successfully treated without any systemic embolic event. Over a median follow-up of 584 days (interquartile range 265-1,165 days), restenosis rates at 1 and 2 years were 35% and 47%, respectively. Multivariate Cox regression analysis revealed devices <7 mm in diameter (hazard ratio [HR] 2.52; 95% confidence interval [CI] 1.04-6.0; P=0.040) and totally occluded lesions (HR 3.33; 95% CI 1.21-9.15; P=0.020) were independent risk factors for restenosis. CONCLUSIONS: All PVS lesions were successfully enlarged by the PV intervention; however, restenosis developed in approximately half the lesions within 2 years.

Changes in pulmonary vein size and narrowing depend on the cardiac cycle before and after pulmonary vein isolation.

Accurate measurement of the pulmonary vein dimension (PVD) is important for determining stenosis and efficacy following pulmonary vein isolation (PVI). Little is known about the quantitative evaluation of the impact of the cardiac cycle on pulmonary vein (PV) morphology before and after PVI. This study aims to investigate variations in the ostial size of the PV during the cardiac cycle before and after PVI and the effect of the cardiac cycle on PV stenosis and reduction rate using cardiac computed tomography (CT). Sixty-eight patients with atrial fibrillation who underwent cardiac CT before and after PVI at our institution between 23 January 2021 and 5 February 2022 were retrospectively analyzed. The maximum and minimum PVD were measured at each segment before and after the PV. Each PV was evaluated according to the PVD reduction rate (ΔPVD), calculated as follows: (1 - post-PVD/pre-PVD) × 100 (%). The average dimension of all PVs at the end-diastolic frame was significantly reduced compared to that at the end-systolic frame before PVI. The average dimensions of the right superior and right inferior PV at the end-diastolic frame were significantly reduced compared with those at the end-systolic frame following PVI. The average reduction rate of dimension-classified stenosis of PVs, except for the left inferior PV at the end-diastolic frame, was significantly reduced compared with that at the end-systolic frame. The cardiac cycle affects PVD assessment, including PV stenosis, after PVI. PVD measurement is recommended to be unified to the end-systolic frame of the cardiac cycle to avoid underestimating PV stenosis before and after PVI, ensuring appropriate management and follow-up.

Utility of simultaneous triple balloon inflation technique through a single 6-French sheath in treating pulmonary vein stenosis.

Pulmonary vein stenosis continues to pose significant challenges in children, frequently requiring repeated cardiac catheterisation procedures. This report describes a successful application of a "triple kissing balloon" technique to treat complex pulmonary vein stenosis in two patients, all accomplished with the use of a single 6-French sheath.

Outcomes and Risk Factors of Interventions for Pediatric Post-operative Pulmonary Vein Stenosis.

Pulmonary vein stenosis (PVS) in children is a challenging condition with poor outcomes. Post-operative stenosis can occur after repair of anomalous pulmonary venous return (APVR) or stenosis within native veins. There is limited data on the outcomes of post-operative PVS. Our objective was to review our experience and assess surgical and transcatheter outcomes. Single-center retrospective study was performed including patients < 18 years who developed restenosis after baseline pulmonary vein surgery that required additional intervention(s) from 1/2005 to 1/2020. Non-invasive imaging, catheterization and surgical data were reviewed. We identified 46 patients with post-operative PVS with 11 (23.9%) patient deaths. Median age at index procedure was 7.2 months (range 1 month-10 years), and median follow-up was 10.8 months (range 1 day-13 years). Index procedure was surgical in 36 (78.3%) and transcatheter in 10 (21.7%). Twenty-three (50%) patients developed vein atresia. Mortality was not associated with number of affected veins, vein atresia, or procedure type. Single ventricle physiology, complex congenital heart disease (CCHD), and genetic disorders were associated with mortality. Survival rate was higher in APVR patients (p = 0.03). Patients with three or more interventions had a higher survival rate compared to patients with 1-2 interventions (p = 0.02). Male gender, necrotizing enterocolitis, and diffuse hypoplasia were associated with vein atresia. In post-operative PVS, mortality is associated with CCHD, single ventricle physiology, and genetic disorders. Vein atresia is associated with male gender, necrotizing enterocolitis, and diffuse hypoplasia. Multiple repeated interventions may offer a patient survival benefit; however, larger prospective studies are necessary to elucidate this relationship further.

Endovascular transatrial stenting of pulmonary vein stenosis after lung transplantation.

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.

Is creation of a fully circumferential lesion set necessary for laser balloon ablation-based pulmonary vein isolation?

BACKGROUND: Despite reports of remote pulmonary vein (PV) stenosis after visually guided laser balloon (VGLB) ablation, circumferential (360°) lesion sets are routinely performed. This study aimed to determine whether fully circumferential lesion creations are required for all PVs to achieve PV isolations (PVIs) and to determine PV's vulnerability to chronic-phase stenosis. METHODS: Fifty-one patients with paroxysmal atrial fibrillation underwent mapping-guided PVIs using circular mapping catheters. VGLB ablation was performed circumferentially beginning at the 12 o'clock position and continued clockwise or counterclockwise. PVIs obtained within the bounds of the first half of the circumferential lesion (≤ 180°) were defined as "early PVIs." RESULTS: "Early PVIs" were documented in real time for 39% (80/204) of the PVs and at a significantly greater frequency among lower PVs than upper PVs (60.1% vs. 17.6%; p < 0.0001). The PV sleeve length, PV diameter, and isolation of ipsilateral PVs within a semicircular lesion set were identified as predictors of an "early PVI" phenomenon. The amount of energy delivered to the lower PVs was significantly less than that to the upper PVs (5553 [5089-6188] vs. 3559 [2793-4380] J; p < 0.0001), but the incidence of narrowing of the lower PVs at 6 months was comparable to that of the upper PVs (p = 0.73). CONCLUSION: Our study revealed electrical isolations of more than 60% of the lower PVs while creating the first half of the circumferential lesions. Crosstalk via the carina region was presumably involved due to the preceding upper PVI. Further study is needed to determine whether energy delivery adjustments are needed for lower PVs to avoid chronic narrowing.

Pulmonary Vein Stenosis-Balloon Angioplasty Versus Stenting: A Systematic Review and Meta-Analysis.

Pulmonary vein stenosis (PVS) may arise from a variety of conditions and result in major morbidity and mortality. In some patients, pharmacologic therapy may help, but more often in advanced stages, mechanical treatment must be considered. Transcatheter approaches, both balloon angioplasty (BA) and stent implantation, have been applied. Although both are effective, they continue to be limited by restenosis. In this systematic review and meta-analysis, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus were searched for English-language studies in humans published between January 1, 2010, and August 2, 2021. Two independent reviewers screened for studies in which BA or stenting was performed for PVS with reporting of restenosis outcomes, and data were independently extracted. A systematic review was performed, and overall restenosis rates were reported across all 34 included studies. Meta-analysis was then performed using RevMan version 5.4, assessing rates of restenosis and restenosis requiring reintervention in those studies with available data reported. For restenosis rates, 4 studies treated a total of 340 patients with 579 pulmonary vein interventions (225 with BA and 354 with stenting, mean follow-up 13-69 months). Restenosis requiring repeat intervention was reported in 3 studies, including 301 patients with 495 pulmonary vein interventions (157 with BA and 338 with stenting). Compared with BA, stenting was associated with both a lower risk for restenosis (risk ratio: 0.36; 95% CI: 0.18-0.73; P = 0.005) and a lower risk for restenosis requiring reintervention (RR: 0.36; 95% CI: 0.15-0.86; P = 0.02). For PVS intervention, restenosis and reintervention rates may be improved by stent implantation compared with BA.

Comparison between cryoballoon and hot balloon ablation in patients with paroxysmal atrial fibrillation.

PURPOSE: Pulmonary vein (PV) isolation using balloon ablation was developed as a technique for patients with paroxysmal atrial fibrillation (PAF). While most studies examined cryoballoon ablation (CBA), there have also been many reports on hot balloon ablation (HBA). We aimed to evaluate the clinical characteristics and outcomes between HBA and CBA. METHODS: In a total of 103 consecutive patients with PAF who underwent catheter ablation, 60 propensity score-matched (30 CBA and 30 HBA) patients were enrolled. The procedural differences and clinical outcomes between the two groups were analyzed. RESULTS: The requirement for additional touch-up ablation was more frequent in the left superior pulmonary vein (LSP) in the HBA group than in the CBA group. Pre-procedural computed tomography (CT) images showed that a thicker left pulmonary vein ridge and larger cross-sectional area of the LSPV were significantly associated with residual PV potentials after HBA. However, post-procedural CT images showed that PV stenosis (> 25%) was higher in the HBA group (33%) than in the CBA group (0%). PV stenosis after HBA was observed most frequently in the right superior PV (50%). The atrial fibrillation/atrial tachycardia-free survival rate during follow-up (365 ± 102 days) was similar between the two groups (CBA vs. HBA, 83% vs. 90%). CONCLUSIONS: Although both balloon modalities can relieve atrial arrhythmia after the procedure, careful attention is required during HBA procedures, especially for the right superior PV, to avoid PV stenosis.

Clinical Outcomes, Predictors, and Surgical Management of Primary Pulmonary Vein Stenosis.

BACKGROUND: Surgical outcomes for primary pulmonary vein stenosis (PPVS) remain unfavorable, and risk factors are still poorly understood. This study evaluated outcomes and risk factors after PPVS repair. METHODS: This retrospective study included 40 patients with PPVS who underwent surgical repair in Fuwai Hospital from 2010 to 2020. Adverse outcomes included overall death, pulmonary vein (PV) restenosis, and reintervention. A univariate and multivariate risk analysis was performed to determine risk factors. RESULTS: The mean follow-up duration was 37.5 ± 31.5 months. Sutureless technique was performed in 7 patients (17.5%), endovenectomy in 9 (22.5%), and patch venoplasty in 24 (60%). Bilateral PV involvement was documented in 12 patients (30%). Overall death, PV reintervention, and restenosis occurred in 15%, 12.5%, and 25% of patients, respectively. Freedom from overall death, PV reintervention, and restenosis at 5 years was 85% ± 6.3%, 88.9% ± 5.2%, and 65.1% ± 13.2%, respectively. Multivariate analysis revealed that bilateral PV involvement was an independent risk factor for death or PV reintervention (hazard ratio, 10.4; 95% confidence interval, 1.9-56; P = .006) and that involvement of the left inferior PV was an independent risk factor for postoperative restenosis of the left inferior PV (hazard ratio, 13.1; 95% confidence interval, 2.2-76.8; P = .004). CONCLUSIONS: Surgical treatment for PPVS remains a challenging issue with imperfect prognosis. Therefore, it is right and appropriate to take close surveillance on mild or moderate stenosis on a single PV. Bilateral and left inferior PV involvement are independent risk factors for adverse outcomes.

Current Endovascular Approach in Adult Patients with Pulmonary Vein Stenosis: A State-of-the-Art Approach.

Regarding to more invasive treatment of atrial arrhythmia (atrial fibrillation ablation) and pulmonary vein isolation (PVI), the rate of acquired pulmonary vein stenosis (PVS) is increasing and at present, PV ablation for AF has become the principal cause of PVS in adult patients. On the other way, by improvement in procedural techniques, equipment, and the experience of the operators, the incidence of PVS has been decreased. There is some controversy about the manner of follow-up of these patients and in most centers, just symptomatic patients are considered for imaging and treatment. Almost always, those with PV stenosis more than 70% or multiple PV involvement become symptomatic and if give them up without treatment, pulmonary symptoms and finally irreversible pulmonary hypertension will occurred. So, intensive pursue after the procedure is highly recommended. Whereas in pediatric patients with congenital or acquired PVS, the best treatment approach is surgery, in adult patients, the preferred type of treatment is the transcatheter intervention with high acute success rate. In this present review, we have scrutinized about the diagnostic modalities, the indications for intervention, the diverse treatment strategies, and principally clarify an accurate stepwise approach during transcatheter procedure.

"Half-uncovered technique" to secure larger stents for postoperative pulmonary vein stenosis.

Although larger stent placement could be effective for pulmonary vein stenosis, stents extrusion tends to occur due to caliber narrowing, small landing area, and the slippery nature. We placed stents with diameter ≧8 mm for four stenotic lesions using the "half-uncovered technique". All stents were precisely placed and successfully resolved the stenosis. This technique allows us to avoid extrusion and to perform safe and effective dilatation when placing larger stents for pulmonary vein stenosis.

Recurrent pneumonia post atrial fibrillation ablation: do not forget to look for pulmonary vein stenosis.

A man in his 50s presented with persistent chest pain, haemoptysis, cough and dyspnoea 5 months after undergoing catheter ablation for atrial fibrillation (AF). Several chest CT scans suggested pneumonia. Despite adequate treatment for recurrent pneumonia, symptoms persisted. While reviewing the initial chest CT, a partial venous infarction of the left lower lobe associated with severe left inferior pulmonary vein stenosis (PVS) was diagnosed. Stenting of the left inferior pulmonary vein with a vascular bare metal stent was performed, guided by fluoroscopy and transoesophageal echocardiography. Dual antiplatelet therapy (aspirin/clopidogrel) was introduced for 3 months, followed by long-term aspirin monotherapy. The treatment resulted in relief of his symptoms and the resolution of pulmonary opacities on chest CT. Despite low frequency, AF ablation remains the most common cause of acquired PVS. As highlighted in this case, symptoms are not specific and include recurrent pulmonary infection with delayed management.