Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Descending aorta to right atrial fistula: Transcatheter embolization of a very rare anomaly with coils.

Key Clinical Message: Descending aorta to right atrial (RA) fistula is a rare and distinct clinical entity mimicking patent ductus arteriosus (PDA) and it may lead to rapid development of pulmonary vascular disease. Correct diagnosis and treatment, especially in the presence of other congenital heart defects, is very important. Interventional management is the treatment of choice. Abstract: We present a case report of a trisomy 21 infant with atrial and ventricular septal defects and small patent ductus arteriosus (PDA) complicated by the presence of descending aorta to right atrial (RA) fistula with large left to right shunt leading to rapid increase in pulmonary vascular resistance. Transcatheter occlusion of the fistula followed by closure of the PDA with Nit-Occlud coil systems led to decreased pulmonary pressure and resistance permitting successful surgical repair of the patient's intracardiac defects with good outcome over 3 years of follow-up. Descending aorta to RA fistula is a rare and distinct clinical entity mimicking PDA and its correct diagnosis and treatment, especially in the presence of other congenital heart defects, is very important as it may lead to rapid development of pulmonary vascular disease.

Efficiency and Safety of Patent Ductus Arteriosus Surgical Ligation in Extremely Low Birth Weight Infants Without Chest Tube Placement.

Patent ductus arteriosus (PDA) has been associated with increased morbidity and mortality in preterm infants. Surgical ligation (SL) is generally performed in symptomatic infants when medical management is contraindicated or has failed. We retrospectively reviewed our institution's experience in surgical management of PDA for extremely low birth weight (ELBW) infants without chest tube placement assessing its efficiency and safety. We evaluated 17 consecutive ELBW infants undergoing SL for symptomatic PDA (January 2012-January 2018) with subsequent follow-up for 6 months postdischarge. Patients consisted of 9 (53%) females and 8 (47%) males. Mean gestational age (GA) at birth was 27.9 ± 2.1 weeks. Median values for surgical age (SA) from birth to operation was 10 days (interquartile range [IQR]: 8-12); PDA diameter 3.4 mm (IQR: 3.2-3.5); surgical weight (SW) 750 g (IQR: 680-850); and days of mechanical ventilation (DMV) as estimated by Kaplan-Meier curve 22 days (95% confidence interval: 14.2-29.8). We observed a statistically significant negative association between DMV and GA at birth (rho = - 0.587, p = 0.017), SA (rho = - 0.629, p = 0.009) and SW (rho = - 0.737, p = 0.001). One patient experienced left laryngeal nerve palsy confirmed by laryngoscopy. Otherwise, there were no adverse events to include surgical-related mortality, recurrence of PDA, or need for chest tube placement during follow-up. SL of PDA in ELBW infants without chest tube placement is both efficient and safe. Universal consensus recommendations for the management of PDA in ELBW neonates are needed. Further study is required regarding the use of the less invasive option of percutaneous PDA closure in ELBW infants.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

BACKGROUND: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. PATIENTS AND METHODS: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. RESULTS: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. CONCLUSIONS: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Acute Kidney Injury Predictors and Outcomes after Cardiac Surgery in Children with Congenital Heart Disease: An Observational Cohort Study.

Acute Kidney Injury (AKI) commonly complicates cardiac surgery in children with congenital heart disease (CHD). In this study we assessed incidence, risk factors, and outcomes of postoperative AKI, while testing the hypothesis that, depending on the underlying diagnosis, there would be significant differences in AKI incidence among different diagnostic groups. We conducted an observational cohort study of children with CHD undergoing cardiac surgery in a single tertiary center between January 2019 and August 2021 (n = 362). Kidney Disease Improving Global Outcome (KDIGO) criteria were used to determine the incidence of postoperative AKI. Diagnosis was incorporated into multivariate models using an anatomic-based CHD classification system. Overall survival was estimated using Kaplan−Meier curves. Log-rank test and adjusted Cox proportional hazard modelling were used to test for differences in survival distributions and determine AKI effect on survival function, respectively. AKI occurred in 70 (19.3%), with 21.4% in-hospital mortality for AKI group. Younger age, lower weight, longer cardiopulmonary bypass time, preoperative mechanical ventilation and diagnostic category were associated with postoperative AKI. Resolution rate was 92.7% prior to hospital discharge for survivors. AKI was associated with longer duration of mechanical ventilation, ICU and hospital length of stay. AKI patients had significantly higher probability of all-cause mortality postoperatively when compared to the non-AKI group (log-rank test, p < 0.001). Adjusted hazard ratio for AKI versus non-AKI group was 11.08 (95% CI 2.45−50.01; p = 0.002). Diagnostic category was associated with cardiac surgery-related AKI in children with CHD, a finding supporting the development of lesion specific models for risk stratification. Postoperative AKI had detrimental impact on clinical outcomes and was associated with decreased survival to hospital discharge.

Association of Health Status Metrics with Clinical Outcomes in Patients with Adult Congenital Heart Disease and Atrial Arrhythmias.

The prognostic value of health status metrics in patients with adult congenital heart disease (ACHD) and atrial arrhythmias is unclear. In this retrospective cohort study of an ongoing national, multicenter registry (PROTECT-AR, NCT03854149), ACHD patients with atrial arrhythmias on apixaban are included. At baseline, health metrics were assessed using the physical component summary (PCS), the mental component summary (MCS) of the Short-Form-36 (SF-36) Health Survey, and the modified European Heart Rhythm Association (mEHRA) score. Patients were divided into groups according to their SF-36 PCS and MCS scores, using the normalized population mean of 50 on the PCS and MCS as a threshold. The primary outcome was the composite of mortality from any cause, major thromboembolic events, major/clinically relevant non-major bleedings, or hospitalizations. Multivariable Cox-regression analyses using clinically relevant parameters (age greater than 60 years, anatomic complexity, ejection fraction of the systemic ventricle, and CHA2DS2-VASc and HAS-BLED scores) were performed to examine the association of health metrics with the composite outcome. Over a median follow-up period of 20 months, the composite outcome occurred in 50 of 158 (32%) patients. The risk of the outcome was significantly higher in patients with SF-36 PCS ≤ 50 compared with those with PCS > 50 (adjusted hazard ratio (aHR), 1.98; 95% confidence interval [CI], 1.02−3.84; p = 0.04) after adjusting for possible confounders. The SF-36 MCS ≤ 50 was not associated with the outcome. The mEHRA score was incrementally associated with a higher risk of the composite outcome (aHR = 1.44 per 1 unit increase in score; 95% CI, 1.03−2.00; p = 0.03) in multivariable analysis. In ACHD patients with atrial arrhythmias, the SF-36 PCS ≤ 50 and mEHRA scores predicted an increased risk of adverse events.

The impact of cardiovascular comorbidities associated with risk for left heart disease on idiopathic pulmonary arterial hypertension: Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or <3 CVCs, arterial hypertension, diabetes mellitus, obesity, presence of coronary artery disease, or atrial fibrillation. Overall, 77 patients with IPAH (55.1 [interquartile range, IQR: 24.1] years, 62.8% women) have been recorded. Fifteen patients (19.2%) had ≥3 CVCs, while 25 (32%) were over 65 years old. Patients with ≥3 CVCs were older, presented an almost equal female to male ratio, walked less in 6-min walk test, and had lower mean arterial pulmonary pressure and pulmonary vascular resistance at baseline than patients with less CVCs. Fewer patients with ≥3 CVCs received PAH-specific treatment compared to patients with less comorbidities (n = 11 [73.3%] versus n = 58 [95.5%], p = 0.02). During a median follow-up period of 3.8 (IQR: 2.7) years, 18 patients died (all-cause mortality 24.3%). Male sex and older age were independent predictors of mortality and/or lung transplantation, while CVCs did not have a significant impact on clinical outcomes. In this nationwide, register-based study, the epidemiology of IPAH involves older patients with CVCs, who seem to have less hemodynamic compromise, but worse functional impairment and are treated less aggressively with PAH pharmacotherapy.

The Adult Congenital Heart Disease Anatomic and Physiological Classification: Associations with Clinical Outcomes in Patients with Atrial Arrhythmias.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). A follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for the outcome in PhyS C and PhyS D were 1.79 (95% CI 0.69 to 4.67) and 8.15 (95% CI 1.52 to 43.59), respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.12 (95% CI 0.37 to 3.41) and 1.06 (95% CI 0.24 to 4.63), respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA.

Radiation Exposure in Pediatric Interventional Procedures.

The article is part of the series of articles on radiation protection. You can find further articles in the special section of the CVIR issue. The expanding applications of interventional procedures coupled with the potential harmful effects of ionizing radiation highlight the need to assess the delivered radiation dose and establish an effective radiation protection program, particularly in the radiosensitive pediatric population. Given the complexity and heterogeneity of interventional procedures as well as the unique characteristics of children, the management of radiation dose is proving to be quite challenging. The aim of the current article is to provide an overview of the radiation exposure in pediatric patients during interventional procedures focusing on the importance of radiation protection in the pediatric population, the reported radiation doses and the techniques of minimizing radiation dose.

Use of the Prostacyclin Receptor Agonist Selexipag in Patients With Pulmonary Arterial Hypertension Associated With Eisenmenger Syndrome.

Eisenmenger syndrome is a multisystem disorder and the most severe form of pulmonary arterial hypertension in adult congenital heart disease. Pulmonary arterial hypertension represents a fatal disease, characterized by increased pulmonary vascular resistance, right heart failure, and death. Although therapeutic management has rapidly advanced in recent years, these patients were not included in randomized controlled trials for specific pulmonary arterial hypertension drugs, except for bosentan. However, in clinical practice we apply treatment strategies combining drugs targeting multiple pathobiological pathways. We present 3 patients with Eisenmenger syndrome and their improvement after starting treatment with selexipag, an oral selective IP prostacyclin receptor agonist.

Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study.

INTRODUCTION: The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA. METHODS AND ANALYSIS: PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a 'real-world' setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03854149; Pre-results.

Multiple myocardial bridges causing severe ischaemia in adolescent with pulmonary stenosis.

Myocardial bridges are often asymptomatic but may need therapy when causing ischaemia. They have rarely been reported in children or in association with CHD, where symptomatology may be mistakenly attributed to the CHD. We report a case of multiple myocardial bridges causing ischaemia in an adolescent with pulmonary stenosis and discuss management.

Reversible right heart failure after redo operation of a post-traumatic Gerbode defect.

INTRODUCTION: Gerbode defect is a rare entity and represents a small percent of all congenital defects. If left untreated, right heart failure may occur. CASE REPORT: We describe a redo case of a 47-year-old patient complaining about the signs and symptoms of decompensating right heart failure after a surgically treated post-traumatic Gerbode defect 8 years prior. DISCUSSION: Although it is described as a congenital defect, in clinical practice, results mostly as an iatrogenic complication after heart valve surgery, endocarditis, nodal ablation, or post-traumatic defect. Surgical correction is the treatment of choice independently of the provided cause. Dimensions, the position of the defect, are very important factors for the interventional approach. At 12 months post-operatively, the patient remained completely asymptomatic. He has an active life and presents all the echocardiographic metrics within normal values. CONCLUSION: We strongly recommend that in cardiac areas where high wall tension is applied, durable materials such as Dacron should be used. We also believe that a well-documented discussion with the patient, about his medical condition and his therapeutic alternatives, is imperative.

Epidemiology and initial management of pulmonary arterial hypertension: real-world data from the Hellenic pulmOnary hyPertension rEgistry (HOPE).

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.

Cardiovascular imaging approach in pre and postoperative tetralogy of Fallot.

Advances in the medical and surgical management of Tetralogy of Fallot have led to marked increase of the number and age of survivors. Imaging in patients with Tetralogy of Fallot plays a crucial role in the diagnosis and follow up, and essentially guides management and intervention in this entity. This study systematically reviews the imaging modalities used in patients with Tetralogy of Fallot in the evaluation of preoperative and postoperative anatomic and hemodynamic lesions, as well as disease progression in this diagnosis. Various invasive and noninvasive imaging modalities, most commonly echocardiography and cardiovascular magnetic resonance, computed tomography and angiocardiography provide the imaging information required for diagnosis, management and follow up in Tetralogy of Fallot. The choice of the appropriate imaging tool or their combination is guided by the clinical question, the patient's clinical condition and contraindications as well as the strengths and weaknesses of each imaging modality. Tetralogy of Fallot is the most common complex congenital heart disease with long term survivors that need close follow up and complicated management, including multiple surgical and transcatheter interventions. Knowledge of the role and protocols of imaging in Tetralogy of Fallot is extremely important for the clinical as well as the imaging physician in order to optimize patients' management and long-term prognosis.

Hospitalisations for heart failure predict mortality in pulmonary hypertension related to congenital heart disease.

OBJECTIVE: Despite the progress in the management of patients with adult congenital heart disease (ACHD), a significant proportion of patients still develop pulmonary hypertension (PH). We aimed to highlight the rate of the complications in PH-ACHD and the predicting factors of cumulative mortality risk in this population. METHODS: Data were obtained from the cohort of the national registry of ACHD in Greece from February 2012 until January 2018. RESULTS: Overall, 65 patients receiving PH-specific therapy were included (mean age 46.1±14.4 years, 64.6% females). Heavily symptomatic (New York Heart Association (NYHA) class III/IV) were 53.8% of patients. The majority received monotherapy, while combination therapy was administered in 41.5% of patients. Cardiac arrhythmia was reported in 30.8%, endocarditis in 1.5%, stroke in 4.6%, pulmonary arterial thrombosis in 6.2%, haemoptysis in 3.1% and hospitalisation due to heart failure (HF) in 23.1%. Over a median follow-up of 3 years (range 1-6), 12 (18.5%) patients died. On univariate Cox regression analysis history of HF hospitalisation emerged as a strong predictor of mortality (HR 8.91, 95% CI 2.64 to 30.02, p<0.001), which remained significant after adjustment for age and for NYHA functional class. CONCLUSIONS: Long-term complications are common among patients with PH-ACHD. Hospitalisations for HF predict mortality and should be considered in the risk stratification of this population.

Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation.

End-stage heart failure (HF) frequently needs continuous inotropic support in hospital and has high morbidity and mortality in absence of heart transplantation. This study reports outcome, efficacy, and safety of continuous ambulatory inotropes (AI) and/or periodic levosimendan (LS) infusions in pediatric HF patients. The study included 27 patients, median age 9.4 (0.1-26.1) years, with severe HF (6 myocarditis, 13 dilated cardiomyopathy, 2 restrictive cardiomyopathy, 6 repaired congenital heart disease). Dobutamine and milrinone AI were administered in 21 patients through a permanent central catheter for median duration 1.0 (0.3-3.7) years. Additionally, 14 AI patients and the remaining 6 study patients received periodic LS infusions for median duration 1.1 (0.2-4.2) years. During median follow-up 2.1 (0.3-21.3) years, 4 patients died of worsening HF after 0.8-2.1 years AI, 6 patients underwent heart transplantation with only 3 survivors, while the rest remained stable out of the hospital with complications 4 line infections treated with antibiotics and 4 catheter reinsertions due to dislodgement. Severe pulmonary hypertension was reversed with AI in 2 patients, allowing successful heart-only transplantation. Therapy with AI was discontinued after 1.4-0.4 years in 6 improved myocarditis and 3 cardiomyopathy patients without deterioration. In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital. It may provide precious time for heart transplantation or myocardial remodeling, improvement, and possible discontinuation even after long periods of support.

Large single centre experience with the Cera™ and CeraFlex™ occluders for closure of interatrial communications: usefulness of the flexible rotation feature.

We present our experience with the Cera (CO) and the CeraFlex occluder (CFO) in transcatheter closure of interatrial communications (IAC). Between 2013 and 2016, 201 patients (75 males, 16 with patent foramen ovale), aged 27 ± 19 (5-75) years, underwent percutaneous closure of IAC using CO or CFO in our institution. After transoesophageal imaging, the procedure was aborted in 7 young paediatric (6-13 years old) patients (3 multiple holes, 3 too small septum, 1 leak with 38 mm occlusion balloon). The occluder was removed prior to release in 11 patients (5.7%), while occlusion was successful in 183 patients (94.3%) with 44 CO, 136 CFO, and 3 Cera multifenestrated occluders. There were no deaths, embolizations, or major complications. Small residual shunts were demonstrated in 8 patients immediately after implantation, 4 (8.5%) with CO and 4 (2.9%) with CFO, all disappearing after 3 months. Over 1.8 ± 1.7 year follow-up, all patients improved with 2 asymptomatic, transient pericardial effusions and 5 adults with transient supraventricular arrhythmias, treated medically for 6 months. IAC closure with CO and CFO proved safe with favourable success rates and few, nonserious complications. The CFO flexible rotation feature helped in conforming to various septal anatomies, minimising manoeuvres and possibly post-occlusion leaks.

The respiratory system in pediatric chronic heart disease.

Cardiovascular disease in the pediatric population closely affects the respiratory system inducing water retention in the lungs and pulmonary edema, airway compression by cardiovascular structures, restrictive pulmonary physiology as a result of hemodynamic changes and surgical repair, susceptibility to respiratory infections, development of pulmonary hypertension, thrombosis, or hemorrhage. Chronic heart failure and congenital heart disease are characterized by various respiratory manifestations and symptoms mimicking lung disease, which are frequently difficult to diagnose and treat. Pulmonary function is multiply affected in pediatric heart disease with mostly restrictive but also obstructive and diffusion abnormalities. Patients with Fontan circulation represent a separate group with slow, passive pulmonary blood flow and distinct pathophysiology with low cardiac output heart failure, restrictive lung pattern, increased thromboembolic complications and rare conditions such as protein losing enteropathy and plastic bronchitis. Distinguishing between cardiovascular and pulmonary symptoms may be challenging in the growing population of pediatric and adult survivors of congenital heart disease and understanding of the relationship of the two systems in heart disease is crucial for the optimal management of these patients.

Pulmonary vasodilator therapy in tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals: case series and review of literature.

We present the use of pulmonary vasodilators in three adult patients with unrepaired tetralogy of Fallot, pulmonary atresia, aortopulmonary collaterals, and segmental pulmonary arterial hypertension. Patients improved by 1-2 NYHA classes with modest exercise-tolerance increase, and remained stable without side effects during 2.5, 10, and 14 years. Literature review revealed five studies with pulmonary vasodilators in heterogeneous, mostly repaired patient populations.