Outcomes of Surgical Repair of Total Anomalous Pulmonary Venous Drainage: Role of Primary Sutureless Technique.

To evaluate the surgical outcomes of total anomalous pulmonary venous drainage focusing on survival, postoperative and pulmonary venous obstruction. Further investigate the role of primary sutureless technique in patients with preoperative pulmonary venous obstruction. Consecutive patients underwent total anomalous pulmonary venous drainage repair in our institution during Jan 2000 to Dec 2019 were enrolled into this retrospective analysis. Since 2016, sutureless repair was regularly applied in patients with preoperative pulmonary venous obstruction. All patients with preoperative pulmonary venous obstruction referred before 2016 had underwent traditional repair. A total of 95 patients were included. During follow-up time of 85 months, main endpoints were documented in 21 patients, including 9 (9.5%) early deaths, 3 (2.3%) late deaths and 9 (9.5%) postoperative pulmonary venous obstructions. Preoperative pulmonary venous obstruction was presented in 26 (27.4%) patients with more emergent surgery (14/26 vs 3/69, P < 0.001) was required. Main endpoints occurred more in patients with preoperative pulmonary venous obstruction (4/26 vs 5/69, P = 0.004). Patients experienced sutureless technique had a lower incidence of postoperative PVO at follow-up (0/11 versus 4/11, P = 0.045). Outcomes of surgical repair for total anomalous venous drainage are satisfactory. However, preoperative pulmonary venous obstruction may be accompanying unfavorable early deaths and postoperative pulmonary venous obstruction. Propensity matching analysis showed that sutureless technique was benefit for postoperative pulmonary venous obstruction without longer cardiopulmonary bypass and aortic cross-clamp time.

Single-institution outcomes of surgical repair of infracardiac total anomalous pulmonary venous connection.

OBJECTIVE: This contemporary study sought to describe the outcomes of patients undergoing biventricular repair of infracardiac total anomalous pulmonary venous connection. METHODS: A retrospective study was performed on patients with infracardiac total anomalous pulmonary venous connection who underwent sutureless technique or conventional repair between 2006 and 2018. Risk factors for survival and post-repair pulmonary vein stenosis (PVS) were assessed with Cox regression model. Time-to-event analysis was conducted using Kaplan-Meier estimates. RESULTS: This study included 82 consecutive patients with the median age of 21 days (interquartile range, 9-40 days). The median follow-up was 29 months (interquartile range, 12.5-59 months) and was available in 95% of the survivors at the end of the study period in 2019. Overall, 8 deaths (8.5%) occurred in the conventional repair group. There was a trend of higher mortality in the conventional repair group, although it did not reach a statistical difference (P = .2). Postrepair PVS occurred at a median of 2 months (interquartile range, 1.2-3.6 months) postoperatively and all occurred in the conventional repair group. Time-to-event analysis with the event of postrepair PVS showed significantly higher freedom from restenosis in the sutureless technique group (P = .0004). Adjusted hazard ratios from time-dependent Cox model described the association between postrepair PVS and pulmonary venous confluence of antler configuration (hazard ratio, 2.14; 95% confidence interval, 1.03-5.47; P = .002) and the use of sutureless technique (hazard ratio, 0.72; 95% confidence interval, 0.39-0.97; P = .003). CONCLUSIONS: Sutureless technique is associated with a lower risk of postrepair PVS in patients with infracardiac total anomalous pulmonary venous connection. pulmonary venous confluence configuration of antler appearance appears to be associated with restenosis and mortality.

Genetic Evaluation in a Cohort of 126 Dutch Pulmonary Arterial Hypertension Patients.

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH.

Rate of acquired pulmonary vein stenosis after ablation of atrial fibrillation referred to electroanatomical mapping systems: Does it matter?

BACKGROUND: Thermal injury during radiofrequency ablation (RFA) of atrial fibrillation (AF) can lead to pulmonary vein stenosis (PVS). It is currently unclear if routine screening for PVS by imaging (echocardiography, computed tomography) is clinically meaningful and if there is a correlation between PVS and the electroanatomical mapping system (EAMS) used for the ablation procedure. It was therefore investigated in the current single center experience. METHODS: All patients from January 2004 to December 2016 with the diagnosis of PVS after interventional ablation of AF by radiofrequency were retrospectively analyzed. From 2004 to 2007, transesophageal echocardiography was routinely performed as screening for RFA-acquired PVS (group A). Since 2008, diagnostics were only initiated in cases of clinical symptoms suggestive for PVS (group B). RESULTS: The overall PVS rate after interventional RFA for AF of the documented institution is 0.72% (70/9754). The incidence was not influenced by screening: group A had a 0.74% PVS rate and group B a 0.72% rate (NS). Referred to as the EAMS, there were significant differences: 20/4229 (0.5%) using CARTO®, 48/4510 (1.1%) using EnSite®, 1/853 (0.1%) using MediGuide®, and 1/162 (0.6%) using Rhythmia®. Since 2009, no significant difference between technologies was found. CONCLUSIONS: The present analysis of 9754 procedures revealed 70 cases of PVS. The incidence of PVS is not related to screening but to the application of different EAMS. Possible explanations are technological backgrounds (magnetic vs. electrical), learning curves, operator experience, and work-flow differences. Furthermore, incorporation of new technologies seems to be associated with higher incidences of PVS before workflows are optimized.

Pharmacovigilance in a rare disease: example of the VIGIAPATH program in pulmonary arterial hypertension.

Spontaneous reporting is the primary method used in pharmacovigilance (PV) to detect drug safety signal. Specific criteria used in pharmacovigilance to prove accountability of a drug are rarely present in rare disease. The low number of alerts also makes it challenging. The aim of this commentary is to raise awareness among pharmacists on issues and opportunities for pharmacovigilance in rare diseases, taking pulmonary arterial hypertension (PAH) as example, from which a subset of cases are drug-induced. It is demonstrated how a dedicated program named VIGIAPATH created to reinforce pharmacovigilance of drug-induced pulmonary arterial hypertension at a national level, led to increase self-reporting and confirm safety signals. Thanks to a specific program such as VIGIAPATH, pharmacists can play an important role in communication with clinicians, patients and regulatory agencies, facilitating the detection of potential safety signals at an early stage in rare disease.

[Pulmonary veno-occlusive disease]. / La maladie veino-occlusive pulmonaire.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterized by preferential remodelling of pulmonary venules and angioproliferation. PVOD term includes idiopathic, heritable (biallelic mutations of EIF2AK4 gene), drugs and toxins induced (alkylating agents, organic solvents) and connectivite-associated forms (especially systemic-sclerosis associated form). PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation. Lung biopsy is contraindicated in PVOD due to high risk of life-threatening bleeding. A noninvasive diagnostic approach, including oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest, is used to support a diagnosis of PVOD. PVOD prognosis is worse than other forms of PAH. There is no evidence-based medical therapy for PVOD and life-threatening pulmonary edema may occur following PAH targeted therapy in PVOD. Lung transplantation remains the preferred definitive therapy for eligible patients.

Long-term outcomes of total correction for isolated total anomalous pulmonary venous connection: lessons from 50-years' experience.

OBJECTIVES: Isolated total anomalous pulmonary venous connection (TAPVC) is a relatively rare congenital cardiac defect, while pulmonary venous obstruction (PVO) is associated with poor prognosis. We reviewed the long-term outcome of total correction for isolated TAPVC at our institute and analysed the risk factors for mortality and morbidity. METHODS: A total of 290 isolated TAPVC patients evaluated between 1965 and 2016 were divided into 2 groups: Group Early (n = 151) underwent surgery before 1989; Group Late (n = 139) underwent surgery after 1990. The mean age at operation was 10.4 ± 30.2 months (range 0 day to 23 years), and the mean body weight was 5.5 ± 6.0 kg (range 1.6-48 kg). Group Late included more patients with the infracardiac type of TAPVC and preferably used the posterior approach. RESULTS: There were 53 hospital deaths and 16 late deaths. Postoperative PVO was recognized in 28 patients. The mean follow-up time was 18.2 ± 9.7 years (range 2 months to 42.4 years). The actuarial survival rate was improved to 87.8% at 20 years in Group Late. Multivariable analysis revealed that death rate was significantly increased in patients of Group Early, with a body weight <2 kg and with postoperative PVO (P < 0.0001, P = 0.0041, P = 0.0003, respectively). Reoperations were performed 27 times in 22 patients (PVO repair, 11; staged repair, 4 and others, 12). PVO repair was performed at a mean of 2.5 ± 1.6 months later. The actuarial freedom from reoperation rates were 88.8% and 83.2% at 20 and 30 years, respectively. Multivariable analysis revealed that the risk of reoperation was associated with mixed-type TAPVC and postoperative PVO (P = 0.0064 and P < 0.0001, respectively). CONCLUSIONS: Long-term surgical outcomes of isolated TAPVC have improved over the past 25 years. Postoperative PVO, the mixed-type TAPVC and a body weight <2 kg might be the important factors contributing to mortality and morbidity.

Respiratory effects of trichloroethylene.

Trichloroethylene (TCE) is a chlorinated solvent that has been used widely around the world in the twentieth century for metal degreasing and dry cleaning. Although TCE displays general toxicity and is classified as a human carcinogen, the association between TCE exposure and respiratory disorders are conflicting. In this review we aimed to systematically evaluate the current evidence for the respiratory effects of TCE exposure and the implications for the practicing clinician. There is limited evidence of an increased risk of lung cancer associated with TCE exposure based on animal and human data. However, the effect of other chlorinated solvents and mixed solvent exposure should be further investigated. Limited data are available to support an association between TCE exposure and respiratory tract disorders such as asthma, chronic bronchitis, or rhinitis. The most consistent data is the association of TCE with autoimmune and vascular diseases such as systemic sclerosis and pulmonary veno-occlusive disease. Although recent data are reassuring regarding the absence of an increased lung cancer risk with TCE exposure, clinicians should be aware of other potential respiratory effects of TCE. In particular, occupational exposure to TCE has been linked to less common conditions such as systemic sclerosis and pulmonary veno-occlusive disease.

Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension characterised by predominant remodelling of pulmonary venules. Bi-allelic mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene were recently described as the major cause of heritable PVOD, but risk factors associated with PVOD remain poorly understood. Occupational exposures have been proposed as a potential risk factor for PVOD, but epidemiological studies are lacking.A case-control study was conducted in consecutive PVOD (cases, n=33) and pulmonary arterial hypertension patients (controls, n=65). Occupational exposure was evaluated via questionnaire interview with blinded assessments using an expert consensus approach and a job exposure matrix (JEM).Using the expert consensus approach, PVOD was significantly associated with occupational exposure to organic solvents (adjusted OR 12.8, 95% CI 2.7-60.8), with trichloroethylene being the main agent implicated (adjusted OR 8.2, 95% CI 1.4-49.4). JEM analysis independently confirmed the association between PVOD and trichloroethylene exposure. Absence of significant trichloroethylene exposure was associated with a younger age of disease (54.8±21.4 years, p=0.037) and a high prevalence of harbouring bi-allelic EIF2AK4 mutations (41.7% versus 0%, p=0.015).Occupational exposure to organic solvents may represent a novel risk factor for PVOD. Genetic background and environmental exposure appear to influence the phenotypic expression of the disease.

Pulmonary venoocclusive disease in childhood.

BACKGROUND: Pulmonary venoocclusive disease (PVOD) is a rare lung disease, diagnosed in 5% to 10% of patients with pulmonary hypertension (PH). The incidence, prevalence, and etiology of PVOD in children are not well defined. The mortality remains high, related, at least partly, to the limited treatment options. METHODS: This retrospective analysis (1985-2011) summarizes symptoms, associated factors, treatment, and outcomes of nine pediatric patients (five girls, four boys) with histologic confirmation of PVOD. RESULTS: PH was diagnosed at a mean age of 13.5 years (range, 8-16 years), followed by the definitive diagnosis of PVOD at a mean age of 14.3 years (range, 10-16 years). Symptoms such as decreased exercise tolerance (n = 6) and/or shortness of breath (n = 9) preceded the diagnosis by 21 months on average; the mean survival time after diagnosis was 14 months (range, 0-47 months). CT scans of the lungs showed typical radiologic features. Treatment included supplemental home oxygen (n = 5), diuretics (n = 9), warfarin (n = 4), and pulmonary vasodilators (n = 4). Four children were listed for lung transplantation, and three have undergone transplantation. Eight patients died, including two after lung transplantation. One patient with lung transplant survived with good quality of life. CONCLUSIONS: PVOD is an important differential diagnosis for pediatric patients with PH. CT scanning is a valuable tool to image lung abnormalities; the definitive diagnosis can only be made by examination of lung biopsy specimens, which subjects the patient to additional risk. Early listing for lung transplantation is essential, as the mean survival time is only 14 months.

Outcome predictors and implications for management of scimitar syndrome.

BACKGROUND: Scimitar syndrome is a rare congenital anomaly. We evaluated risk factors for postoperative pulmonary vein stenosis or death and predictive factors for survival without scimitar vein surgery in patients with scimitar syndrome. METHODS: The records of patients with scimitar syndrome evaluated at our medical center between 1964 and 2011 were reviewed. RESULTS: Scimitar syndrome was identified in 80 patients, with a median follow-up of 4.5 years. Patients presenting less than 1 year of age had a higher incidence of symptoms, aortopulmonary collaterals, coexisting congenital heart disease (CHD), extracardiac anomalies, and pulmonary hypertension. Of 36 patients having scimitar vein surgery, 18 had postoperative pulmonary vein obstruction that occurred with similar frequency after baffle or reimplantation procedures, early or late in the study period, and tended to be more common in infants (P = .10). Overall, 19 (24%) of 80 died. Multivariate risk factors for death included systolic pulmonary pressure >0.5 systemic level (P = .007) and left pulmonary vein stenosis (P = .009). Pulmonary artery systolic pressure <0.5 systemic level (P = .01) and absence of CHD excluding atrial septal defect (P = .01) were predictive factors in 28 patients who survived and did not have scimitar vein surgery; these patients had no or mild right ventricular dilation and a ratio of pulmonary-to-systemic flow <1.6 either at baseline, after coiling aortopulmonary collaterals or nonscimitar vein intervention. CONCLUSIONS: Postoperative pulmonary vein obstruction is common after scimitar vein surgery regardless of redirection technique. Pulmonary hypertension and left pulmonary vein stenosis are risk factors for death, whereas patients without significant pulmonary hypertension or associated CHD did well without scimitar vein surgery. These observations may guide management decisions in patients with scimitar syndrome.

Survival in pulmonary hypertension in Spain: insights from the Spanish registry.

A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial Hypertension) was undertaken to analyse prevalence, incidence and survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Spain, and to assess the applicability of recent survival prediction equations. Voluntary reporting of previously diagnosed and incident PAH or CTEPH cases (July 2007-June 2008) was performed. Demographic, functional and haemodynamic variables were evaluated. 866 patients with PAH and 162 with CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno-occlusive disease were reported for the first time in a PAH registry. Estimated prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9 cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%, respectively, with no differences between PAH and CTEPH. Male sex, right atrial pressure and cardiac index were independent predictors of death. Matching between observed survival and that predicted by different equations was closer when the characteristics of the cohorts were similar. Epidemiology and survival of PAH patients in the Spanish registry are similar to recent registries. Characteristics of the population from which survival prediction equations are derived influence their applicability to a different cohort. CTEPH is much less prevalent than PAH, although has a similar survival rate.

Prevalence, characteristics, and predictors of pulmonary vein narrowing after isolation using the pulmonary vein ablation catheter.

BACKGROUND: The risk of pulmonary vein narrowing (PVN) after pulmonary vein isolation, using a novel multi-electrode ablation catheter, is unknown. METHODS AND RESULTS: Left atrial volume and PV diameters were compared by computed tomography (CT) before and 3 months after pulmonary vein isolation using duty-cycled phased radio frequency energy (2:1 or 4:1 bipolar/unipolar ratio) in 50 patients. Pulmonary vein diameter was measured in a coronal and axial view at 3 levels (A, ostium; B, 1 cm more distal; C, 2 cm more distal). Moderate PVN was defined as a pulmonary vein diameter reduction of 25 to 50%, and severe PVN as >50%. Left atrial volume decreased by 12±12% (P<0.01). Axial pulmonary vein diameter shortened by a median of 16% (interquartile range [IQR] 28 to 5%), 13% (IQR 25 to 5%), and 9% (IQR 21 to -3%) at level A, B, and C, respectively (P<0.01 for all); coronal pulmonary vein diameter decreased by a median of 16% (IQR 24 to 7%), 11% (IQR 21 to 4%), and 8% (IQR 18 to -2%; P<0.01 for all). Moderate PVN occurred in 30% of the PVs, in 78% of the patients; severe PVN occurred in 4% of the PVs, in 15% of the patients. PV diameter reduction was not related to changes in left atrial volume. CONCLUSIONS: Isolation of the pulmonary veins using a multielectrode ablation catheter and duty cycled phased radiofrequency energy delivery results in a consistent moderate reduction of the PV diameters predominantly at the ostium. Severe PVN in 15% of patients raises concerns about the risk for clinical PV stenosis.

Pulmonary veno-occlusive disease: advances in clinical management and treatments.

Pulmonary veno-occlusive disease (PVOD) is a rare disorder that can be misdiagnosed as idiopathic pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered as idiopathic PAH. PVOD and idiopathic PAH share a similar clinical presentation, genetic background and hemodynamic profile. A definite diagnosis of PVOD necessitates a surgical biopsy, but since it represents a high-risk procedure in these patients, it is contraindicated. Therefore, a noninvasive diagnostic approach using chest high-resolution computed tomography, arterial blood gas analysis, pulmonary function tests and bronchoalveolar lavage is helpful to detect PVOD. PVOD is characterized by a poor prognosis and the possibility of developing severe pulmonary edema with specific PAH therapy. Lung transplantation remains the treatment of choice.

Pulmonary veno-occlusive disease: the bête noire of pulmonary hypertension in connective tissue diseases?

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension that may develop in patients with connective tissue diseases (CTD). Most cases have been reported in patients with systemic sclerosis, though associations with systemic lupus erythematosis and mixed connective tissue disease have also been described. PVOD is characterised by progressive obstruction of small pulmonary veins and venules that leads to increased pulmonary vascular resistance, right heart failure and premature death. Distinguishing PVOD from pulmonary arterial hypertension (PAH) is often difficult, though use of a diagnostic algorithm may improve diagnostic accuracy and preclude recourse to lung biopsy. The finding of normal left-heart filling pressures in the context of radiological studies suggestive of pulmonary oedema is an important diagnostic clue, particularly if this clinical scenario coincides with the introduction of vasodilator therapy. There are no approved treatments for the disorder, though cautious use of PAH specific therapy may improve short-term outcomes in selected idiopathic PVOD cases. This review summarises the epidemiologic, clinico-pathologic and imaging characteristics of PVOD in the setting of CTD and discusses potential management approaches.

Total anomalous pulmonary venous connection: morphology and outcome from an international population-based study.

BACKGROUND: late mortality after repair of total anomalous pulmonary venous connection is frequently associated with pulmonary venous obstruction (PVO). We aimed to describe the morphological spectrum of total anomalous pulmonary venous connection and identify risk factors for death and postoperative PVO. METHODS AND RESULTS: we conducted a retrospective, international, collaborative, population-based study involving all 19 pediatric cardiac centers in the United Kingdom, Ireland, and Sweden. All infants with total anomalous pulmonary venous connection born between 1998 and 2004 were identified. Cases with functionally univentricular circulations or atrial isomerism were excluded. All available data and imaging were reviewed. Of 422 live-born cases, 205 (48.6%) had supracardiac, 110 (26.1%) had infracardiac, 67 (15.9%) had cardiac, and 37 (8.8%) had mixed connections. There were 2 cases (0.5%) of common pulmonary vein atresia. Some patients had extremely hypoplastic veins or, rarely, discrete stenosis of the individual veins. Sixty (14.2%) had associated cardiac anomalies. Sixteen died before intervention. Three-year survival for surgically treated patients was 85.2% (95% confidence interval 81.3% to 88.4%). Risk factors for death in multivariable analysis comprised earlier age at surgery, hypoplastic/stenotic pulmonary veins, associated complex cardiac lesions, postoperative pulmonary hypertension, and postoperative PVO. Sixty (14.8%) of the 406 patients undergoing total anomalous pulmonary venous connection repair had postoperative PVO that required reintervention. Three-year survival after initial surgery for patients with postoperative PVO was 58.7% (95% confidence interval 46.2% to 69.2%). Risk factors for postoperative PVO comprised preoperative hypoplastic/stenotic pulmonary veins and absence of a common confluence. CONCLUSIONS: preoperative clinical and morphological features are important risk factors for postoperative PVO and survival.

Transesophageal echocardiography for the diagnosis of pulmonary vein stenosis after catheter ablation of atrial fibrillation: a systematic review.

AIMS: Pulmonary vein (PV) stenosis is a potentially serious complication of catheter ablation of atrial fibrillation (AF). The optimal method for diagnosis of PV stenosis has not been established. We undertook a systematic review of the literature to investigate the diagnostic performance of transesophageal echocardiography (TEE) for the detection of PV stenosis after catheter ablation of AF. METHODS: We searched MEDLINE and EMBASE databases for studies evaluating the diagnostic performance of TEE for the detection of PV stenosis after catheter ablation of AF, compared to a reference standard of PV angiography, magnetic resonance imaging (MRI), or computed tomography (CT). Study quality was assessed using the QUADAS tool. RESULTS: A total of seven studies that included 344 patients (1,344 PVs) met the selection criteria. Of these, three studies used PV angiography as the reference standard, while MRI and CT were used in two studies each. Compared to PV angiography, TEE had sensitivity between 82% and 100% and specificity between 98% and 100%. Compared to MRI, TEE sensitivity was 100% in both studies, while the specificity ranged between 98% and 99%. Compared to CT, TEE had sensitivity between 86% and 100% and specificity of 95%. Quality of the reviewed studies was somewhat limited by the retrospective design in most of the studies. CONCLUSIONS: TEE has a high sensitivity and specificity in detecting PV stenosis. Given its wide availability and favorable side effect profile, these data suggest that TEE is very useful tool for the diagnosis of PV stenosis after catheter ablation of AF.