Improving Outcomes in Pulmonary Vein Stenosis: Novel Pursuits and Paradigm Shifts.

Pulmonary vein stenosis (PVS) remains a clinical challenge, with progressive restenosis being common. In the past five years, we have seen an exponential increase in both clinical and scientific publication related to PVS. Central to progress in PVS clinical care is the paradigm shift towards collaborative, multidisciplinary care that utilizes a multimodality approach to treatment. This manuscript will discuss recent conceptual gains in PVS treatment and research while highlighting important outstanding questions and barriers.

Pathogenesis, Evaluation, and Management of Pulmonary Vein Stenosis: JACC Review Topic of the Week.

Pulmonary vein stenosis (PVS) can arise from several etiologies, including congenital, acquired, and iatrogenic sources. PVS presents insidiously, leading to significant delays in diagnosis. A high index of suspicion and dedicated noninvasive evaluation are key to diagnosis. Once diagnosed, both noninvasive and invasive evaluation may afford further insights into the relative contribution of PVS to symptoms. Treatment of underlying reversible pathologies coupled with transcatheter balloon angioplasty and stenting for persistent severe stenoses are established approaches. Ongoing refinements in diagnostic modalities, interventional approaches, postintervention monitoring, and medical therapies hold promise to further improve patient outcomes.

Management of Complex Pulmonary Vein Stenosis at Altitude Combining Comprehensive Percutaneous Interventional Treatment with Sirolimus, Pulmonary Hypertension Medications and Intraluminal Imaging with Optical Coherence Tomography.

BACKGROUND: Pulmonary vein stenosis (PVS) is a growing problem for the pediatric congenital heart population. Sirolimus has previously been shown to improve survival and slow down the progression of in-stent stenosis in patients with PVS. We evaluated patients before and after initiation of sirolimus to evaluate its effects on re-intervention and vessel patency utilizing Optical Coherence Tomography (OCT). METHODS: We performed a retrospective study, reviewing the charts of patients with PVS, who had been prescribed sirolimus between October 2020 and December 2021. OCT was performed in the pulmonary vein of interest as per our published protocol. Angiographic and OCT imaging was retrospectively reviewed. Statistical analysis was performed using Chi square and Wilcoxon signed-rank test to compare pre-and post-sirolimus data. RESULTS: Ten patients had been started and followed on sirolimus. Median age at sirolimus initiation was 25 months with median weight of 10.6 kg and average follow-up of 1 year. Median total catheterizations were 7 for patients prior to starting sirolimus and 2 after starting treatment (p = 0.014). Comparing pre- and post-sirolimus, patients were catheterized every 3 months vs every 11 months (p = 0.011), median procedure time was 203 min vs 145 min (p = 0.036) and fluoroscopy time, 80 min vs 57.2 min (p = 0.036). 23 veins had severe in-stent tissue ingrowth prior to SST (luminal diameter < 30% of stent diameter). Post-sirolimus, 23 pulmonary veins had moderate to severe in-stent tissue ingrowth that responded to non-compliant balloon inflation only with stent luminal improvement of > 75%. CONCLUSION: Our study suggests that the addition of sirolimus in patients with moderate-severe PVS helps to decrease disease progression with decrease frequency of interventions. Reaching therapeutic levels for sirolimus is critical and medication interactions and side-effects need careful consideration. OCT continues to be important for evaluation and treatment guidance in this patient population.

Cardiovascular magnetic resonance pulmonary perfusion for guidance of interventional treatment of pulmonary vein stenosis.

BACKGROUND: Pulmonary vein (PV) stenosis represents a rare but serious complication following radiofrequency ablation of atrial fibrillation with a comprehensive diagnosis including morphological stenosis grading together with the assessment of its functional consequences being imperative within the relatively narrow window for therapeutic intervention. The present study determined the clinical utility of a combined, single-session cardiovascular magnetic resonance (CMR) imaging protocol integrating pulmonary perfusion and PV angiographic assessment for pre-procedural planning and follow-up of patients referred for interventional PV stenosis treatment. METHODS: CMR examinations (cine imaging, dynamic pulmonary perfusion, three-dimensional PV angiography) were performed in 32 consecutive patients prior to interventional treatment of PV stenosis and at 1-day and 3-months follow-up. Degree of PV stenosis was visually determined on CMR angiography; visual and quantitative analysis of pulmonary perfusion imaging was done for all five lung lobes. RESULTS: Interventional treatment of PV stenosis achieved an acute procedural success rate of 90%. Agreement between visually evaluated pulmonary perfusion imaging and the presence or absence of a ≥ 70% PV stenosis was nearly perfect (Cohen's kappa, 0.96). ROC analysis demonstrated high discriminatory power of quantitative pulmonary perfusion measurements for the detection of ≥ 70% PV stenosis (AUC for time-to-peak enhancement, 0.96; wash-in rate, 0.93; maximum enhancement, 0.90). Quantitative pulmonary perfusion analysis proved a very large treatment effect attributable to successful PV revascularization already after 1 day. CONCLUSION: Integration of CMR pulmonary perfusion imaging into the clinical work-up of patients with PV stenosis allowed for efficient peri-procedural stratification and follow-up evaluation of revascularization success.

Pulmonary Vein Angioplasty for Pulmonary Vein Stenosis After Ablation Therapy for Atrial Fibrillation　- A Report of 7 Cases.

BACKGROUND: Pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is rare; however, it remains a serious complication. PV angioplasty is reportedly an effective therapy; however, a dedicated device for PV angioplasty has not been developed, and the detailed procedural methods remain undetermined. This study describes the symptoms, indications, treatment strategies, and long-term outcomes for PV stenosis after AF ablation.Methods and Results: This study retrospectively analyzed 7 patients with PV stenosis after catheter ablation for AF and who had undergone PV angioplasty at our hospital during 2015-2021. PV stenosis occurred in the left superior (5 patients) and left inferior (2 patients) PV. Six patients had hemoptysis, chest pain, and dyspnea. Seven de novo lesions were treated using balloon angioplasty (BA) (3 patients), a bare metal stent (BMS) (3 patients), and a drug-coated balloon (DCB) (1 patient). The restenosis rate was 42.9% (n=3; 2 patients in the BA group and 1 patient in the DCB group). The repeat treatment rate was 28.6% (2 patients in the BA group). Stenting was performed as repeat treatment. One patient with subsequent repeat restenosis development underwent BA. Ten PV angioplasties were performed; there were no major complications. CONCLUSIONS: Regarding PV angioplasty after ablation therapy for AF, stenting showed superior long-term PV patency than BA alone; therefore, it should be considered as a standard first-line approach.

Transcatheter Recanalization of Atretic Pulmonary Veins in Infants and Children.

BACKGROUND: Pulmonary vein stenosis is a progressive disease associated with a high rate of mortality in children. If left untreated, myofibroblastic proliferation can lead to pulmonary vein atresia (PVA). In our experience, transcatheter recanalization has emerged as a favorable interventional option. We sought to determine the acute success rate of recanalization of atretic pulmonary veins and mid-term outcomes of individual veins after recanalization. METHODS: We reviewed all patients with PVA at our institution between 2008 and 2020 diagnosed by either catheterization or cardiac computed tomography. All veins with successful recanalization were reviewed and procedural success rate and patency rate were noted. Competing risk analysis was performed to demonstrate outcomes of individual atretic veins longitudinally. RESULTS: Between 2008 and 2020, our institution diagnosed and treated 131 patients with pulmonary vein stenosis. Of these, 61 patients developed atresia of at least one pulmonary vein. In total, there were 97 atretic pulmonary veins within this group. Successful recanalization was accomplished in 47/97 (48.5%) atretic veins. No atretic pulmonary veins were successfully recanalized before 2012. The majority of veins were recanalized between 2017 and 2020-39/56 (70%). The most common intervention after recanalization was drug-eluting stent placement. At 2-year follow-up 42.6% of recanalized veins (20.6% of all atretic veins) remained patent with a median of 4 reinterventions per person. CONCLUSIONS: Transcatheter recanalization of PVA can result in successful reestablishment of flow to affected pulmonary veins in many cases. Drug-eluting stent implantation was the most common intervention performed immediately post-recanalization. Vein patency was maintained in 42.6% of patients at 2-year follow-up from recanalization with appropriate surveillance and reintervention. Overall, only a small portion of atretic pulmonary veins underwent successful recanalization with maintained vessel patency at follow-up. Irrespective of successful recanalization, there was no detectable survival difference between the more recently treated PVA cohort and non-PVA cohort.

Pulmonary vein stenosis: Anatomic considerations, surgical management, and outcomes.

OBJECTIVE: The study objective was to evaluate outcomes of pulmonary vein stenosis repair in a large single-center cohort. METHODS: Clinical data from a pulmonary vein stenosis registry were retrospectively reviewed identifying patients who underwent pulmonary vein stenosis repair. The primary/index operation was defined as the patient's first pulmonary vein stenosis operation during the study period. RESULTS: Between January 2007 and August 2019, 174 patients underwent pulmonary vein stenosis repair. Bilateral pulmonary vein stenosis occurred in 111 patients (64%); 71 patients (41%) had 4-vessel disease. Fifty-nine patients (34%) had primary pulmonary vein stenosis. Median age was 9 months (interquartile range, 5-27) and weight was 6.5 kg (4.7-10.2). Surgical techniques evolved and included ostial resection, unroofing, reimplantation, sutureless, modified sutureless, and a newer anatomically focused approach of pulmonary vein stenosis resection with lateralization or patch enlargement of the pulmonary vein-left atrium connection. Twenty-three patients (13%) required reoperation. Cumulative 2-year incidence of postoperative transcatheter intervention (balloon dilation ± stenting) was 64%. One-, 2-, and 5-year survivals were 71.2%, 66.8%, and 60.6%, respectively. There was no association between surgery type and reoperation rate (hazard ratio, 2.38, P = .25) or transcatheter intervention (hazard ratio, 0.97, P = .95). The anatomically focused repair was associated with decreased mortality on univariate (hazard ratio, 0.38, P = .042) and multivariable analyses (hazard ratio, 0.19, P = .014). Antiproliferative chemotherapy was also associated with decreased mortality (hazard ratio, 0.47, P = .026). CONCLUSIONS: This large single-center surgical pulmonary vein stenosis experience demonstrates encouraging midterm results. A new anatomically focused repair strategy aims to alleviate pulmonary vein angulation to minimize turbulence and shows promising early outcomes. Continued follow-up is required to understand longer-term outcomes for this surgical approach.

Primary pulmonary vein stenosis during infancy: state of the art review.

Primary pulmonary vein stenosis (PPVS) is an emerging problem among infants. In contrast to acquired disease, PPVS is the development of stenosis in the absence of preceding intervention. While optimal care approaches remain poorly characterized, over the past decade, understanding of potential pathophysiological mechanisms and development of novel therapeutic strategies are increasing. A multidisciplinary team of health care providers was assembled to review the available evidence and provide a common framework for the diagnosis, management, and treatment of PPVS during infancy. To address knowledge gaps, institutional and multi-institutional approaches must be employed to generate knowledge specific to ex-premature infants with PPVS. Within individual institutions, creation of a team comprised of dedicated health care providers from diverse backgrounds is critical to accelerate clinical learning and provide care for infants with PPVS. Multi-institutional collaborations, such as the PVS Network, provide the infrastructure and statistical power to advance knowledge for this rare disease.

Primary pulmonary vein stenosis among premature infants with single-vessel disease.

OBJECTIVES: Describe outcomes among preterm infants diagnosed with single-vessel primary pulmonary vein stenosis (PPVS) initially treated using conservative management (active surveillance with deferral of treatment). STUDY DESIGN: Retrospective cohort study at a single, tertiary-center (2009-2019) among infants <37 weeks' gestation with single-vessel PPVS. Infants were classified into two categories: disease progression and disease stabilization. Cardiopulmonary outcomes were examined, and a Kaplan-Meier survival analysis performed. RESULTS: Twenty infants were included. Compared to infants in the stable group (0/10, 0%), all infants in the progressive group had development of at least severe stenosis or atresia (10/10, 100%; P < 0.01). Severe pulmonary hypertension at diagnosis was increased in the progressive (5/10, 50%) versus the stable group (0/10, 0%; P = 0.03). Survival was lower among infants in the progressive than the stable group (log-rank test, P < 0.01). CONCLUSION: Among preterm infants with single-vessel PPVS, risk stratification may be possible, wherein more targeted, individualized therapies could be applied.

The many faces and outcomes of pulmonary vein stenosis in early childhood.

Pulmonary vein stenosis is a rare and poorly understood condition causing obstruction of the large pulmonary veins and of blood flow from the lungs to the left atrium. This results in elevated pulmonary venous pressure and pulmonary edema, pulmonary hypertension, potentially cardiac failure, and death. Clinical signs of the disease include failure to thrive, increasingly severe dyspnea, hemoptysis, respiratory difficulty, recurrent respiratory tract infections/pneumonia, cyanosis, and subcostal retractions. On chest radiograph, the most frequent finding is increased interstitial, ground-glass and/or reticular opacity. Transthoracic echocardiography with pulsed Doppler delineates the stenosis, magnetic resonance imaging and multislice computerized tomography are used for further evaluation. Interventional cardiac catherization, surgical techniques, and medical therapies have been used with varying success as treatment options.

Treatment of Congenital and Acquired Pulmonary Vein Stenosis.

PURPOSE OF REVIEW: Pulmonary vein stenosis (PVS) is a rare entity that until the last 2 decades was seen primarily in infants and children. Percutaneous and surgical interventions have limited success due to relentless restenosis, and mortality remains high. In adults, acquired PVS following ablation for atrial fibrillation has emerged as a new syndrome. This work will review these two entities with emphasis on current treatment. RECENT FINDINGS: Greater emphasis on understanding and addressing the mechanism of restenosis for congenital PVS has led to the use of drug-eluting stents (DES) and systemic drug therapy to target neo-intimal growth. Frequent reinterventions are positively affecting outcomes. Longer-term outcomes of percutaneous treatment for acquired PVS are emerging. Treatment of congenital PVS continues to be plagued by restenosis. DES show promise, but frequent reinterventions are required. Larger upstream vein diameter predicts success for congenital and acquired PVS interventions. Efforts to induce/maintain vessel growth are important for future treatment strategies.

Combined pulmonary vein stenosis stenting and left atrial appendage occlusion in a patient with hemoptysis after atrial fibrillation ablation.

BACKGROUND: Pulmonary vein stenosis (PVS) after radiofrequency ablation for non-valvular atrial fibrillation (AF) is an uncommon but serious complication. PVS stenting can rapidly restore pulmonary flow and improve symptoms with long-term low incidence of restenosis. However, high risk of thrombosis remains if AF is recurrent, especially for CHA2DS2-VASc > 2. CASE PRESENTATION: A 67-year-old man with diabetes, hypertension and a history of stroke underwent radiofrequency pulmonary vein isolation for persistent AF 1 year ago. Six months later he developed recurrent respiratory infection and massive hemoptysis. Computed tomography pulmonary angiography revealed severe left pulmonary vein stenosis. Simultaneous percutaneous PVS stenting and left atrial appendage occlusion were performed to resolve recurrent hemoptysis and prevent stroke. The clinical follow-up indicated a good short and mid-term result with significant improvement of symptoms. CONCLUSIONS: Simultaneous PVS stenting and left atrial appendage occlusion is feasible and effective in patients with recurrence of AF and hemoptysis induced by radiofrequency ablation for AF.

[Feasibility and efficacy of percutaneous pulmonary vein stenting for the treatment of patients with severe pulmonary vein stenosis due to fibrosing mediastinitis].

Objective: To evaluate the feasibility and safety percutaneous pulmonary vein intervention in patients with severe pulmonary vein stenosis (PVS) caused by fibrosing mediastinitis(FM). Methods: This retrospective analysis included 5 FM patients (2 male, 3 female, 54-77 years old) confirmed by clinical presentation and chest computed tomography (CT) scan from January to June 2018 who were from Gansu Provincial Hospital and Shanghai Chest Hospital. CT pulmonary angiography (CTPA) further revealed severe PVS caused by fibrotic tissue compression in mediastinum. After selective pulmonary vein angiography, gradually balloon angioplasty was used to expand the pulmonary vein and then stents were implanted in the pre-dilated stenotic pulmonary veins. Evaluation of therapeutic effect was made at 6 months after the procedure. Results: All of 11 serious compression PVS were treated with stent implantation (diameter: 7-10 mm, length: 17-27 mm). After stenting, degree of pulmonary vein stenosis decreased from (83±16)% to (12±4)% (P<0.01). The minimal diameter of the stenotic pulmonary vein was significantly increased from (0.8±0.5)mm to (7.5±0.8)mm (P<0.01). Trans-stenotic gradient decreased from (27.0±15.1)mmHg (1 mmHg=0.133 kPa) to (2.50±0.58)mmHg (P<0.05). Mean pulmonary pressure measured by cardiac catheter decreased from (45.0±9.0)mmHg to (38.7±8.4)mmHg (P<0.05). One patient experienced cardiac arrest due to vagal nerve reflex during big sizing balloon stent dilation and recovered after cardiopulmonary resuscitation. There were no other serious procedure related complications. During the follow-up, severe stenosis at end of proximal stent was evidenced in 1 patient due to fibrotic compression, and another patient developed in-stent thrombosis due to discontinuation of prescribed anticoagulant. Conclusion: Percutaneous intervention for severe pulmonary vein stenosis caused by FM is feasible and safe, and can improve hemodynamic caused by the compression of mediastinal vascular structures in these carefully selected patients.

Bilateral pulmonary vein stenting for treatment of massive hemoptysis caused by pulmonary vein stenosis following catheter ablation for atrial fibrillation.

BACKGROUND: Massive hemoptysis is a life-threatening condition. Massive hemoptysis caused by pulmonary vein stenosis (PVS) after radiofrequency catheter ablation for atrial fibrillation (AF) is rare. However, bilateral lung hemorrhage following bilateral PVS is extremely rare. CASE PRESENTATION: We herein describe a 62-year-old man with refractory massive hemoptysis after radiofrequency catheter ablation for AF, which was successfully controlled by surgical lobectomy and endovascular bilateral PV stenting. The hemorrhage was derived from the bilateral lungs following PV obstruction and bilateral PVS, which was definitively diagnosed by bronchoscopic examination. The patient had no recurrence of hemoptysis during a follow-up period of 30 months, and the PV stents had not narrowed as shown by computed tomography 30 months after stent placement. CONCLUSIONS: Massive hemoptysis can be caused by bilateral PVS after radiofrequency catheter ablation for AF, and hemorrhage from the bilateral lungs in such patients is extremely rare. Nevertheless, cardiologists, interventional radiologists, and pulmonologists should consider the potential for massive hemoptysis caused by PVS.

Comparison of drug eluting versus bare metal stents for pulmonary vein stenosis in childhood.

OBJECTIVE: Comparison of outcomes using bare metal (BMS) and drug-eluting (DES) stents in pulmonary vein stenosis (PVS). BACKGROUND: PVS is a serious condition with frequent restenosis after surgical and percutaneous interventions. After experiencing encouraging results with DES, we sought to compare outcomes of BMS and DES in native and post-surgical PVS. METHODS AND RESULTS: A retrospective review of all patients who underwent stent implantation between 08/93 and 11/17 for PVS at Texas Children's Hospital was performed. BMS were used to treat 58 lesions in 37 patients and 105 DES used to treat 105 lesions in 41 patients. Mean age at first stent implant was 2.9 ± 3.5 years in BMS and 16.2 ± 18.8 months in DES group. Of those with follow-up catheterization, mean lumen loss rate from stent implant to first follow-up catheterization was 0.85 ± 1.47 mm/month over 6.4 ± 6.4 months in the BMS group (n = 44 lesions) compared to 0.16 ± 0.31 mm/month over 6.8 ± 7.4 months in the DES group (n = 86 lesions), p < .01. Follow-up for the BMS group was 14 months (6 days-22.3 years), with 13 mortalities, eight lesions were re-stented and six complete occlusions were noted. Follow-up for DES group (including four cross-overs) was 17.5 months (3 days-9 years), with 10 mortalities, seven lesions were re-stented, 11 had complete occlusion, 20 new adjacent lesions in the same vessel underwent stenting and 12 stents were intentionally fractured. CONCLUSION: DES have significantly lowered lumen loss rate when compared to BMS at medium term follow-up and can be fractured to enable larger diameters. Availability of larger diameter DES would be ideal.