A 24-Year-Old Woman With Dyspnea, Chest Pain, and Dry Cough.

CASE PRESENTATION: A 24-year-old woman, a baby-sitter with no known comorbidities, presented to the outpatient department with complaints of modified Medical Research Council grade IV breathlessness for 3 months, chest pain, and dry cough for 2 weeks. There was no known disease history, including respiratory, flu-like illness, or connective tissue disorder. There was no use of chemotherapeutic, oral contraceptive drugs, exposure to toxic substances, or smoking. A review of systems was negative for fever, arthralgia, myalgia, Raynaud phenomenon, skin thickening, rash, or leg swelling. The patient had no family history suggestive of a genetic syndrome.

Variable Expressivity of a Founder Mutation in the EIF2AK4 Gene in Hereditary Pulmonary Veno-occlusive Disease and Its Impact on Survival.

INTRODUCTION AND OBJECTIVES: Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course. METHODS: Observational study of Romani patients with familial PVOD included in the Spanish Registry of Pulmonary Arterial Hypertension. Genetic screening of EIF2AK4 was performed in index cases and relatives between November 2011 and July 2016 and histological pulmonary examination was carried out in patients who received a lung transplant or died. The patients were divided into 2 groups depending on their tolerance to PVD, with comparison of baseline characteristics and survival free of death or lung transplant. RESULTS: Eighteen Romani patients were included: 9 index cases and 9 relatives. The biallelic founder mutation in EIF2AK4 was found in all affected cases and 2 unaffected relatives. Family screening showed 34.2% of healthy heterozygotes, high consanguinity, young age at childbirth, and frequent multiparity. Prognosis was bleak, with significant differences depending on tolerance to PVD. CONCLUSIONS: We describe 2 phenotypes of hereditary PVOD depending on tolerance to PVD, with prognostic impact and familial distribution. Consanguinity may have a negative impact on the transmission of PVOD, with familial genetic screening showing high effectiveness.

Functional total anomalous pulmonary venous connection via levoatriocardinal vein.

We report a fetal case of double outlet right ventricle, mitral atresia, and intact atrial septum. Although the pulmonary veins were connected to the left atrium, pulmonary venous blood drained into the right superior vena cava via the stenotic levoatriocardinal vein (LACV), which resulted in a circulation resembling total anomalous pulmonary venous connection (TAPVC) with pulmonary venous obstruction. Since the pulmonary veins were connected to both the stenotic LACV and the "dead-end" left atrium, the pulmonary venous flow had a to-and-fro pattern along with atrial relaxation and contraction. Postnatal echocardiography and computed tomography confirmed the diagnosis of normally connected but anomalously draining pulmonary veins via the LACV. Surgical creation of an atrial septal defect on the day of birth successfully relieved pulmonary venous obstruction. Normally connected but anomalously draining pulmonary veins via the LACV should be considered for TAPVC differential diagnosis in fetuses with a left-side heart obstruction.

Congenital Pulmonary Vein Stenosis: Encouraging Mid-term Outcome.

Congenital pulmonary vein stenosis (PVS) is a rare entity with limited outcome literature. Multiple interventional approaches have evolved including surgical and catheterization techniques. Our objective is to report our center experience and to compare short-term and mid-term outcomes among these therapeutic modalities. Retrospective study on 23 patients (n = 23) with PVS that required intervention over the last 13 years (2000-2013). Patients were divided into three groups based on type of initial intervention. Of these, 10 (43.5%) had balloon angioplasty, 3 (13.0 %) had surgical dilation, and 10 (43.5%) had surgical marsupialization. Mortality and number of re-interventions were our primary outcomes. Mean age at diagnosis was 10.9 ± 18.4 months. Mean age at initial intervention was 14.5 ± 18.0 months. Mean pre- and post-initial intervention PVS gradients were 9.2 ± 3.4 and 3.4 ± 2.2 mmHg, respectively. Mean survival time and re-intervention-free survival time were 4.8 ± 4.0 and 2.8 ± 3.4 years. No statistical significance was found between the interventions with respect to survival time (p = 0.52) and re-intervention free time (p = 0.78). High initial pre- and post-intervention gradients were significantly associated with re-intervention-free survival (p = 0.01 and p = 0.03, respectively). Patients with bilateral disease have increased mortality (p = 0.01) and decreased 5-year survival (p = 0.009) compared to patients with unilateral disease irrespective of type of intervention. No statistically significant difference in mortality or re-intervention rate was present among these different therapeutic modalities. This study has the longest follow-up so far reported in the current literature (58 months) with overall survival of 78%.

Total anomalous pulmonary venous connection with ccTGA and VSD: Can pulmonary artery banding avert pulmonary venous obstruction?

We describe a rare case of infracardiac total anomalous pulmonary venous connection (TAPVC), associated with congenitally corrected transposition of the great arteries (ccTGA) and ventricular septal defect, in which the patient had undergone pulmonary artery banding (PAB) at 16 days of age. She began to have episodes of severe cyanosis while crying, 2 weeks after PAB. Cardiac catheterization at 34 days of age showed severe pulmonary hypertension and a transhepatic pressure gradient of 7 mmHg. The infant underwent TAPVC repair and conventional repair for ccTGA at 35 days of age. Although PAB might have the provisional effect of delaying the manifestation of pulmonary venous obstruction (PVO), it is unable to prevent the development of PVO due to the high resistance of the hepatic sinusoids. Signs of PVO should be closely monitored so that TAPVC can be repaired in a timely fashion.

MRI shows limited mixing between systemic and pulmonary circulations in foetal transposition of the great arteries: a potential cause of in utero pulmonary vascular disease.

OBJECTIVES: To investigate the relationship between foetal haemodynamics and postnatal clinical presentation in patients with transposition of the great arteries using phase-contrast cardiovascular magnetic resonance. BACKGROUND: A severe and irreversible form of persistent pulmonary hypertension of the newborn occurs in up to 5% of patients with transposition and remains an important cause of morbidity and mortality in these infants. Restriction at the foramen ovale and ductus arteriosus has been identified as a risk factor for the development of pulmonary hypertension, and this can now be studied with magnetic resonance imaging using a new technique called metric optimised gating. METHODS: Blood flow was measured in the major vessels of four foetuses with transposition with intact ventricular septum (gestational age range: 35-38 weeks) and compared with values from 12 normal foetuses (median gestational age: 37 weeks; range: 34-40 weeks). RESULTS: We found significantly reduced flows in the ductus arteriosus (p<0.01) and foramen ovale (p=0.03) and increased combined ventricular output (p=0.01), ascending aortic (p=0.001), descending aortic (p=0.03), umbilical vein (p=0.03), and aorto-pulmonary collateral (p<0.001) flows in foetuses with transposition compared with normals. The foetus with the lowest foramen ovale shunt and highest aorto-pulmonary collateral flow developed fatal pulmonary vascular disease. CONCLUSIONS: We found limited mixing between the systemic and pulmonary circulations in a small group of late-gestation foetuses with transposition. We propose that the resulting hypoxia of the pulmonary circulation could be the driver behind increased aorto-pulmonary collateral flow and contribute to the development of pulmonary vascular disease in some foetuses with transposition.

Primary pulmonary vein stenosis in a premature infant without bronchopulmonary dysplasia: a case report.

Primary pulmonary vein stenosis (PVS) presenting in childhood is uncommon and is related to premature with bronchopulmonary dysplasia (BPD). Here we present a premature infant with primary PVS and without BPD. In our case, a 19-month-old girl was diagnosed with PVS, atrial septal defect and patent arterial duct by echocardiography and selective pulmonary artery angiography. Interestingly in the first 2 month after birth, there was no clue of PVS by bed echocardiography in the patient. It is important to focus on the pulmonary vein blood velocity in premature infants and very low birth weight infants even without BPD.

Lung transplant is a viable treatment option for patients with congenital and acquired pulmonary vein stenosis.

BACKGROUND: Congenital pulmonary vein stenosis (PVS) is associated with high mortality because surgical repair is usually not feasible or is ineffective. In addition, acquired PVS after repair of congenital heart disease is a potential complication that occurs in 5% to 10% of patients and carries a poor prognosis. Lung transplantation has been proposed as a viable option. However, long-term outcomes after lung transplant in these patients remain unknown. METHODS: This was a retrospective review of prospectively maintained database. RESULTS: Between 1990 and 2010, 20 patients (12 girls, 8 boys) with PVS underwent transplantation. Of these, 8 had acquired stenosis from prior repair for total anomalous pulmonary venous return and 1 from atrioventricular canal repair. The median waiting time was 26 days. The mean age at transplant was 1.1 ± 0.89 years, and 16 of the 20 patients were white. All patients received bilateral lung transplants on cardiopulmonary bypass. Four patients (20%) were receiving extracorporeal membrane oxygenation (ECMO) support before transplant, and 3 (15%) required ECMO after transplant due to graft dysfunction. The mean intensive care unit stay was 33.5 ± 29.1 days, and the mean hospital stay was 58.7 ± 43.5 days. The 30-day mortality was 10%. ECMO support in the peri-operative period was the main predictor of 30-day and 1-year mortality (hazard ratio, 3.6; p = 0.01). The overall 5-year survival of the entire cohort was 59.8% (67.3% congenital vs 50.7% acquired). The predominant cause of long-term mortality was bronchiolitis obliterans. The 5-year bronchiolitis obliterans-free survival was 48% (57.2% congenital vs 41% acquired). CONCLUSION: Lung transplant is a viable treatment option for PVS, particularly for patients with diffuse disease or failed surgical correction.

Congenital narrowing of a pulmonary vein: slit-like pulmonary vein ostium.

We report the case of a 60-year-old female with a history of refractory paroxysmal atrial fibrillation. Preablation contrast enhanced pulmonary vein computed tomography (CT) scan demonstrated a slit-like narrowing of the left inferior pulmonary vein ostium. The narrowing measured approximately 3 mm, with poststenotic dilation. The patient had no prior history of ablation. The patient subsequently underwent segmental antral isolation of all four pulmonary veins and cavo-tricuspid isthmus ablation with bidirectional block. The diagnosis of preexisting congenital pulmonary vein stenosis had an impact on the type of ablation procedure performed (antral rather than ostial) and will affect the interpretation of postablation CT scans.

Serum levels after everolimus-stent implantation and paclitaxel-balloon angioplasty in an infant with recurrent pulmonary vein obstruction after repaired total anomalous pulmonary venous connection.

Everolimus-eluting stents and paclitaxel-coated balloons are used in the interventional treatment of coronary artery disease in adults to reduce the restenosis rate and in small-vessel disease. Both substances are released into the circulation. We report systemic drug exposure after implantation of one everolimus-eluting stent and dilation with one paclitaxel-coated balloon in an 8-month-old infant, which was used as an innovative therapy for recurrent pulmonary vein stenosis.

Total anomalous pulmonary venous drainage complicated by tracheoesophageal fistula.

We provided emergency treatment to a 1-day-old neonate (1600 g) with tracheoesophageal fistula (gross classification, type C) and total anomalous pulmonary venous drainage (infracardiac type) complicated by pulmonary venous obstruction. Emergency surgery was required because the tracheoesophageal fistula would have caused respiratory failure. Here we report the perioperative management techniques we used, including the surgical strategy.

Early outcomes of primary sutureless repair of the pulmonary veins.

BACKGROUND: The "sutureless" repair technique has improved outcomes for post-repair pulmonary vein (PV) stenosis. The purpose of this study is to determine the early outcomes of primary sutureless repair of pulmonary venoocclusive disease in infants with congenital PV stenosis-hypoplasia or PVs at high risk for progressive stenosis. METHODS: This is a retrospective review of infants who had primary sutureless repair of the PVs from October 2002 to April 2010. RESULTS: Twenty-five infants had primary sutureless repair of the PVs. Eighteen infants had total anomalous pulmonary venous return; 14 with obstruction, 10 with heterotaxy syndrome, and 9 with univentricular anatomy. Seven infants had congenital PV stenosis. There were 24 perioperative survivors (96%; 95% confidence interval [CI], 75% to 99%) and 2 late deaths from extracardiac causes. Follow-up was available on 21 out of 22 survivors at a median duration of 34 months (range, 9 to 100 months). Persistence-recurrence of PV stenosis occurred in 3 veins (3%) of 2 infants (8%). On follow-up echocardiography, right ventricular systolic pressure was normal in 13 out of 14 infants with a biventricular heart and 60% of systemic blood pressure in 1 infant. Kaplan-Meier 1-year cumulative survival was 88% (95% CI, 66% to 96%). Kaplan-Meier cumulative disease-free survival was 96% (95% CI, 75% to 99%) at 30 days and 84% (95% CI, 58% to 95%) at 1 year. By Cox proportional hazards, age, univentricular anatomy, and atrial isomerism-heterotaxy syndrome were not associated with an increased risk of death or persistence-recurrence. One-year disease-free survival was lower in infants with prematurity (p=0.0055) and low birth weight (p=0.0011). CONCLUSIONS: Primary sutureless repair is a feasible, safe, and relatively effective method of addressing congenital PV stenosis and (or) high-risk PVs, particularly in infants with single ventricle anatomy and (or) heterotaxy syndrome.

Isolated congenital left-sided pulmonary vein stenosis in an adult patient misdiagnosed as primary pulmonary hypertension.

Pulmonary vein stenosis (PVS) is a rare condition, seen usually in association with congenital heart disease or secondary to various acquired causes. Isolated PVS, in adults, especially in absence of congenital heart disease is extremely uncommon. We report PVS of left sided pulmonary veins in an 18-year-old male, who had been till then diagnosed as primary pulmonary hypertension (PPH).

Congenital pulmonary vein stenosis in an adult patient treated with transcatheter balloon angioplasty.

Congenital pulmonary vein stenosis (PVS) is a very rare cardiac malformation and commonly associated with cardiac or extracardiac abnormalities. It is usually found during the newborn period and survival to maturity is very rare due to either of progressive pulmonary hypertension or associated cardiac anomalies. In this case report, an adult patient with congenital PVS that was incidentally found during an evaluation for pneumonia, was treated with balloon angioplasty. After balloon angioplasty, the pressure gradient between the stenotic pulmonary vein and left atrium was significantly reduced and this patient had a benign course during the routine follow-up. Although there is no consensus concerning the optimal treatment strategy for this anomaly, balloon angioplasty can be a reasonable therapeutic option for the palliation of adult congenital PVS.

Comparison of conventional and cutting balloon angioplasty for congenital and postoperative pulmonary vein stenosis in infants and young children.

BACKGROUND: Pulmonary vein stenosis (PVS) is a rare and often lethal condition in children. The optimal treatment for congenital and postoperative PVS is unknown. METHODS AND RESULTS: We compared outcomes of conventional balloon angioplasty performed for PVS from 1999 to 2003 against cutting balloon angioplasty performed from 2004 to 2007. A total of 100 previously undilated pulmonary veins in 54 patients were studied: 48 veins dilated with conventional balloons and 52 with cutting balloons. Acute results included significantly reduced gradients and increased lumen diameters with both treatments. Acutely, cutting balloon angioplasty and conventional angioplasty yielded similar relative reduction of the PVS gradient (median 78% vs. 63%, P = 0.08) and increase in lumen diameter (median 77% vs. 59%, P = 0.07). There was one procedural death of a critically ill infant, and four cardiac arrests, but no adverse events necessitating surgical intervention. Survival free from reintervention was poor in both groups, and shorter in the cutting balloon group (73% at 1 month, 11% at 6 months, and 4% at 1 year) than in the conventional angioplasty group (77% at 1 month, 35% at 6 months, and 23% at 1 year; P = 0.01). CONCLUSIONS: Both conventional and cutting balloon angioplasty were effective at decreasing gradient and increasing lumen size acutely in patients with congenital and postoperative PVS, but reintervention was common with both treatments. Both methods of angioplasty provided limited benefit, and neither was curative for this complex disease.

Non-invasive assessment of congenital pulmonary vein stenosis in children using cardiac-non-gated CT with 64-slice technology.

BACKGROUND: Management of congenital pulmonary vein stenosis is a diagnostic challenge. Echocardiography may be insufficient and thus cardiac catheterization remains the reference standard in this setting. The aim of the study was to investigate the accuracy of cardiac-non-gated CT using 64-slice technology in detecting congenital pulmonary vein stenosis in children. MATERIALS AND METHODS: CT examinations were consecutively performed from May 2005 to December 2006 in 13 children aged 1.5-12 months (median 5 months) for suspected congenital pulmonary vein stenosis. Cardiac-non-gated CT acquisitions were performed after the peripheral injection of contrast agent. Pulmonary veins were evaluated for their pattern of connectivity from the lung to the left atrium and for the presence of stenosis. CT findings of pulmonary vein stenosis were compared with combined findings available from echocardiography, catheterization and surgery. RESULTS: Pulmonary veins from the right lung (n=29) and left lung (n=26) were evaluated as separate structures (N=55). Of the 55 structures, 32 had surgical and/or catheterization data and 45 had echocardiography for comparison. CT visualized 100% (55/55) of the investigated structures, while echocardiography visualized 82% (45/55). In the 13 subjects CT identified 10 stenotic pulmonary veins. CT confirmed the echocardiography suspicion of pulmonary vein stenosis in 100% (7/7) and established a new diagnosis in 3 other patients. CT agreed with surgery/catheterization in 100% (10/10) of the available comparisons. CONCLUSION: Cardiac-non-gated CT assessed the pulmonary veins more completely than echocardiography and should be considered as a viable alternative for invasive pulmonary venography for detecting pulmonary vein stenosis in children.

Primary repair of infracardiac total anomalous pulmonary venous connection using a modified sutureless technique.

Primary repair of infracardiac total anomalous pulmonary venous connection is associated with a significant risk of recurrent pulmonary venous obstruction. Herein we describe a technique of primary repair in which a modified sutureless anastomosis is constructed by suturing the left atrium to the posterior mediastinal pleura that surrounds the pulmonary venous confluence.

Congenital pulmonary vein stenosis.

A case of a newborn infant is described who presented with severe cyanosis at birth with rapid deterioration. The infant died at six hours of life. The diagnosis was determined at autopsy as congenital pulmonary vein stenosis.

Double-outlet right ventricle with left malposition of the great arteries and total anomalous pulmonary venous connection.

The patient was diagnosed with double-outlet right ventricle with left malposition of the great arteries, total anomalous pulmonary venous connection, and pulmonary stenosis at 2 months of age. Because the progression of pulmonary venous obstruction was suspected at 2 years of age, the patient was catheterized and underwent a definitive repair. The patient had a right aortic arch and left juxtaposition of the atrial appendages; the intraventricular anatomy exhibits malalignment between the conal septum and the muscular intraventricular septum, and the conal septum is well developed and dextroposed, resulting in pulmonary obstruction and multiple ventricular septal defects (VSDs). Because a supracardiac type (Darling's type Ib) of total anomalous pulmonary venous connection was also combined with such an anomaly, total correction consisted of an anastomosis of the left atrium and the common pulmonary vein, creation of an intraventricular tunnel, direct closures of muscular VSDs, pulmonary valvotomy, and infundibular resection. To our knowledge, this is the first description of the successful surgical correction of this type of anomaly in one stage.