Severe Pulmonary Regurgitation Research Articles

A CASE OF RIGHT HEART FAILURE: WHEN IT IS NOT PULMONARY EMBOLISM

Abstract A 66–year–old patient, showing exertional dyspnea and atypical chest pain, came to our attention with instrumental findings at echocardiogram of right ventricular failure and was hospitalized due to worsening signs and symptoms of right heart failure. Signs of right ventricular strain and the McGinn–White sign (S1Q3T3 pattern) were seen on the ECG, leading to the suspicion of pulmonary thromboembolism (PE). Pulmonary CT angiography confirmed bilateral PE involving the main pulmonary artery. Oral anticoagulant therapy was initiated with initial partial benefit and relief of symptoms. However, after four weeks, the patient was readmitted for severe heart failure and signs of low cardiac output. Echocardiography showed the presence of a conspicuous, mobile, isoechoic mass occupying most of the main pulmonary artery, suggesting thrombosis. The patient underwent urgent surgical thromboendoarterectomy extended to the third segmental left branches and to the second segmental right branches of the pulmonary artery; a severe pulmonary valve regurgitation was observed and therefore the valve was replaced with a Edwards–Magna pericardial bioprosthetic valve. ECMO (Extracorporeal Membrane Oxygenation) was initiated due to haemodinac instability. In the postoperative period, the severe heart failure worsened, unresponsive to pharmacological treatments and mechanical support, leading to the patient passing away in the following days. Unexpectedly, histological analysis of the surgical specimen revealed neoplastic cells with vascular/endothelial differentiation; fluorescence in situ hybridization (FISH) detected the MDM2 gene (cfr.23–F–00275), involved in the p53 protein regulation mechanisms, which is consistent with a diagnosis of angiosarcoma. Pulmonary–artery angiosarcomas are extremely rare (few anecdotical cases are described in literature) and resemble the CT–signs and clinical features of PE, seriously delaying the diagnosis. They are usually associated with a worse prognosis than PE, one and a half months survival time when inoperable. Radical surgery, associated with thirty six and a half months survival time, is often unfeasible because of locally advanced disease or metastatic disease already present at diagnosis. The main differences with PE are the more proximal and almost–occluding involvement of the pulmonary artery, the absence of peripheral vein thrombosis and the absence of response to anticoagulant therapy.

Machine Learning Quantification of Pulmonary Regurgitation Fraction from Echocardiography.

Assessment of pulmonary regurgitation (PR) guides treatment for patients with congenital heart disease. Quantitative assessment of PR fraction (PRF) by echocardiography is limited. Cardiac MRI (cMRI) is the reference-standard for PRF quantification. We created an algorithm to predict cMRI-quantified PRF from echocardiography using machine learning (ML). We retrospectively performed echocardiographic measurements paired to cMRI within 3months in patients with ≥ mild PR from 2009 to 2022. Model inputs were vena contracta ratio, PR index, PR pressure half-time, main and branch pulmonary artery diastolic flow reversal (BPAFR), and transannular patch repair. A gradient boosted trees ML algorithm was trained using k-fold cross-validation to predict cMRI PRF by phase contrast imaging as a continuous number and at > mild (PRF ≥ 20%) and severe (PRF ≥ 40%) thresholds. Regression performance was evaluated with mean absolute error (MAE), and at clinical thresholds with area-under-the-receiver-operating-characteristic curve (AUROC). Prediction accuracy was compared to historical clinician accuracy. We externally validated prior reported studies for comparison. We included 243 subjects (median age 21years, 58% repaired tetralogy of Fallot). The regression MAE = 7.0%. For prediction of > mild PR, AUROC = 0.96, but BPAFR alone outperformed the ML model (sensitivity 94%, specificity 97%). The ML model detection of severe PR had AUROC = 0.86, but in the subgroup with BPAFR, performance dropped (AUROC = 0.73). Accuracy between clinicians and the ML model was similar (70% vs. 69%). There was decrement in performance of prior reported algorithms on external validation in our dataset. A novel ML model for echocardiographic quantification of PRF outperforms prior studies and has comparable overall accuracy to clinicians. BPAFR is an excellent marker for > mild PRF, and has moderate capacity to detect severe PR, but more work is required to distinguish moderate from severe PR. Poor external validation of prior works highlights reproducibility challenges.

May 2024 Medical Image of the Month: Hereditary Hemorrhagic Telangiectasia in a Patient on Veno-Arterial Extra-Corporeal Membrane Oxygenation

No abstract available. Manuscript truncated after 150 words. A 54-year-old man with a complex cardiac history, including Tetralogy of Fallot requiring Blalock-Taussig shunt in infancy, infundibular patch repair at age 7, and bioprosthetic tricuspid valve replacement at age 52, had ongoing frequent hospitalizations with decompensated right ventricular heart failure secondary to native pulmonary valve mixed stenosis plus regurgitation and left pulmonary artery stenosis. His case was further complicated by his history of hereditary hemorrhagic telangiectasia (HHT) with recurrent epistaxis and recent GI bleeds with multiple angiodysplastic lesions throughout the stomach, duodenum, and descending colon which were previously treated with argon plasma coagulation. The patient was admitted to our hospital in NYHA class IV heart failure receiving a continuous dopamine infusion and aggressive diuresis. Upon admission, a right heart catheterization demonstrated severe pulmonary valve regurgitation, left pulmonary artery stenosis, and systemic hypoxemia suggestive of an intrapulmonary shunt. Admission transthoracic echocardiogram demonstrated normal left ventricular ejection fraction of 55-60%, a …

Exercise Capacity and Reoperation Late After Transatrial Fallot Repair

The exercise capacity long after repair of tetralogy of Fallot, when performed exclusively with a transatrial repair, is unclear. It is also unknown whether echocardiography and cardiopulmonary exercise testing can predict the risk of reoperation in this patient group. We retrospectively reviewed the clinical records of 59 patients who underwent cardiopulmonary exercise testing after transatrial Fallot repair at a single centre. Patients underwent cardiopulmonary exercise testing at a mean age of 16.6±4.4 years, and at 15.3±4.1 years after Fallot repair. At testing, the volume of oxygen consumption at maximal exercise (VO2 max) was 71%±13% and the oxygen pulse was 80%±17% of predicted values. Seventeen (17) patients (29%) had a VO2 max superior to 80% of the predicted value. Thirty-two (32) patients (56%) had severe pulmonary regurgitation, three (5%) had moderate pulmonary regurgitation, and 12 (21%) had mild pulmonary regurgitation. After a mean of 7.8±3.9 years following cardiopulmonary exercise testing (23±5.3 years after the repair), 21 (40%) patients underwent reoperation. Right ventricular dilation and systolic function on echocardiography were both significantly associated with subsequent reoperation rates. Patients who had severe right ventricular dilation were eight times more likely to undergo subsequent reoperation (hazard ratio 8.67; 1.82-41.3; p=0.007). No cardiopulmonary exercise testing variable independently predicted reoperation. The exercise capacity at adolescence following transatrial repair of tetralogy of Fallot is maintained at around 70% of predicted values. Only the patients with normal right ventricular size and normal right ventricular function seemed to be protected from reoperation over the subsequent decade. We found no exercise variables which predicted reoperation.

The effects of pregnancy in subjects with repaired tetralogy of Fallot

BackgroundPrevious reports reveal inconsistent findings of right ventricular (RV) changes following pregnancy in subjects with repaired tetralogy of Fallot (rTOF). MethodsA two-center, retrospective cohort study which included women with rTOF who completed pregnancy that were matched to nulliparous women with rTOF by age at the time of baseline cardiac magnetic resonance (CMR), RV ejection fraction (RVEF), and indexed RV end-diastolic volume (RVEDVi). Pre-pregnancy and postpartum cardiac magnetic resonance (CMR) were analyzed and compared to sequential CMR of nulliparous subjects with rTOF. ResultsThirty-six women with rTOF who completed pregnancy were matched to 72 nulliparous women with rTOF. Over a mean period of 3.1 years for the pregnancy group and 2.7 years for the comparison group, there was no significant change in the RVEDVi, RVEF, RV mass, pulmonary regurgitation severity, left ventricular (LV) volumes, LV ejection fraction (LVEF), or LV mass when comparing the baseline CMR and the follow-up CMR in either of the groups. There was a slight increase in RV indexed end-systolic volume (RVESVi) when comparing the baseline CMR and the follow-up CMR in the pregnancy group (68.93, SD 23.34 ml/m2 at baseline vs. 72.97, SD 25.24 mL/m2 at follow-up, P = .028). Using a mixed effects model for CMR parameters change over time; when adjusted for time between baseline and follow-up CMR there was no significant difference in rate of change between the pregnancy and comparison groups. ConclusionsMost ventricular remodeling parameters measured by CMR did not significantly change in subjects with rTOF who completed pregnancy or in nulliparous subjects with rTOF. In the pregnancy group, RVESVi is larger in those individuals who have undergone pregnancy without a significant change in ventricular function. These patients should be followed longitudinally to determine the long-term ventricular and clinical effects of pregnancy.

Severe Residual Pulmonary Stenosis after Surgical Repair of Tetralogy of Fallot: What’s Our Next Strategy?

This case report describes a 25-year-old woman with Tetralogy of Fallot (TOF) who underwent surgical repair at age 15. Eight years later, she presented with recurrent chest pain and was found to have residual severe pulmonary stenosis and regurgitation. This is a complication of TOF repair, particularly when the pulmonary valve is not preserved. The paper discusses the management of TOF, including initial palliative procedures and complete repair surgery. It highlights the long-term complications such as pulmonary valve regurgitation and residual stenosis, both of which may require re-intervention. The importance of long-term follow-up for TOF patients is emphasized.

Surgically repaired tetralogy of Fallot in the 7th decade: a late presentation of severe pulmonic regurgitation.

Surgically repaired tetralogy of Fallot (TOF) is a congenital heart disease with a cumulative survival rate of 72% in the 4th decade of life in longitudinal single-cohort studies. Debate surrounds conservative versus surgical management in adults with TOF once pulmonary regurgitation occurs. A 73-year-old male with surgically corrected TOF presented with heart failure symptoms. He underwent ToF repair with a classic right Blalock-Taussig shunt at 2years of age with transannular patching at 18years of age. Echocardiography revealed elevated right ventricular systolic pressures, severe right ventricular dilatation, and pulmonary regurgitation. Our patient's new-onset right-sided heart failure was managed medically with diuresis. He received a new pulmonic valve via percutaneous approach on a later planned hospitalization with resolution of symptoms and improved tricuspid regurgitation. It is a class I recommendation for pulmonic valve intervention once greater than moderate PR occurs; however, medical optimization should take place first. Following adequate RV load optimization, our patient underwent successful transcatheter pulmonic valve implantation with resolution of symptoms and cessation of diuretic.

PHYSICAL AND MECHANICAL PROPERTIES OF CONDUITS DURING THE FORMATION OF THE OUTFLOW TRACT INTO THE PULMONARY ARTERY

HighlightsWe have evaluated the rigidity and distensibility of conduits in the long-term period using transthoracic echocardiography. The assessment of elastic properties will make it possible to predict degenerative changes in the conduit and choose the optimal prosthesis. AbstractAim. To evaluate changes in the rigidity and distensibility of conduits in patients after the formation of an outflow tract into the pulmonary artery in comparison with the control group of “healthy” children.Methods. The prospective non-randomized two-center study included 58 people with right ventricular dysfunction who underwent primary conduit implantation between the ages of 3 and 15 years. To assess the elastic properties of the pulmonary artery, a control group of 25 patients (healthy children who agreed to participate in the study) was introduced. The study was carried out at the Meshalkin National Medical Research Center and the Almazov National Medical Research Centre. All patients were divided into 4 groups: healthy children (n = 25), formation of the outflow tract with a pulmonary homograft (n = 28), and formation of the outflow tract with Contegra conduit (n = 19), formation with a xenopericardial conduit (n = 11).Results. The only differences between the groups were the RV EDV index, RV CVD index, RV FIP, severe pulmonary regurgitation, and tricuspid regurgitation. There is a significant difference between the groups in the long-term period (after 12 and 24 months), both in terms of rigidity and elasticity. The only difference in the long-term period after 12 months was the degree of tricuspid regurgitation, which was significantly lower in the control group. After 24 months, the peak gradient between the right ventricle and the pulmonary artery was different, which was significantly higher in the group of xenopericardial conduits and the degree of pulmonary regurgitation, which was significantly lower in the control group.Conclusion. The conduits show higher stiffness in the long-term period in contrast to the normal pulmonary artery, which may affect the durability of the conduits.

Predictors of Atrial Arrhythmia in Adults with Repaired Tetralogy of Fallot.

Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease in adults, has excellent long-term survival. However, many patients (30-45%) develop late arrhythmias. Previous studies have identified predictors of arrhythmia (atrial or ventricular) using clinical markers that predate arrhythmia onset by many years. Our objective was to develop a predictive model for incident atrial arrhythmias within two years of clinical evaluation and diagnostic testing. A single-center nested unmatched case-control study of 174 adults with repaired TOF. We included only patients with results from ECG and echocardiogram data in the required time interval (3-24 months before first arrhythmia for cases; 24 months of follow-up for controls). A predictive multivariable model for risk of incident atrial arrhythmia was developed using logistic regression with a least absolute shrinkage and selection operator (LASSO). Of 41 demographic, surgical, and diagnostic variables, six were selected as having predictive value for atrial arrhythmia based on cross validation. The factors with the greatest predictive value in decreasing order were moderate / severe tricuspid regurgitation (adjusted odds ratio (OR) 149.42), QRS fragmentation (OR 28.08), severe pulmonary regurgitation (OR 8.22), RV systolic dysfunction (OR 2.95), 1st degree AV block (OR 2.59), and age at time of surgical repair (OR 1.02). Predictors for atrial arrhythmia in our study suggested abnormal right ventricle anatomical function and electrophysiologic properties (conduction and repolarization) as the primary underlying substrate.

Optimizing percutaneous pulmonary valve implantation with patient-specific 3D-printed pulmonary artery models and hemodynamic assessment.

Percutaneous pulmonary valve implantation (PPVI) has emerged as a less invasive alternative for treating severe pulmonary regurgitation after tetralogy of Fallot (TOF) repair in patients with a native right ventricular outflow tract (RVOT). However, the success of PPVI depends on precise patient-specific valve sizing, the avoidance of oversizing complications, and optimal valve performance. In recent years, innovative adaptations of commercially available cardiovascular mock loops have been used to test conduits in the pulmonary position. These models are instrumental in facilitating accurate pulmonic valve sizing, mitigating the risk of oversizing, and providing insight into the valve performance before implantation. This study explored the utilization of custom-modified mock loops to implant patient-specific 3D-printed pulmonary artery geometries, thereby advancing PPVI planning and execution. Patient-specific 3D-printed pulmonary artery geometries of five patients who underwent PPVI using Pulsta transcatheter heart valve (THV) ® were tested in a modified ViVitro pulse duplicator system®. Various valve sizes were subjected to 10 cycles of testing at different cardiac output levels. The transpulmonary systolic and regurgitation fractions of the valves were also recorded and compared. A total of 39 experiments were conducted using five different patient geometries and several different valve sizes (26, 28, 30, and 32 mm) at 3, 4, and 5 L/min cardiac output at heart rates of 70 beats per minute (bpm) and 60/40 systolic/diastolic ratios. The pressure gradients and regurgitation fractions of the tested valve sizes in the models were found to be similar to the pressure gradients and regurgitation fractions of valves used in real procedures. However, in two patients, different valve sizes showed better hemodynamic values than the actual implanted valves. The use of 3D printing technology, electromagnetic flow meters, and the custom-modified ViVitro pulse duplicator system® in conjunction with patient-specific pulmonary artery models has enabled a comprehensive assessment of percutaneous pulmonic valve implantation performance. This approach allows for accurate valve sizing, minimization of oversizing risks, and valuable insights into hemodynamic behavior before implantation. The data obtained from this experimental setup will contribute to advancing PPVI procedures and offer potential benefits in improving patient outcomes and safety.

Early Outcomes of Pulmonary Valve Replacement With the Edwards Inspiris Resilia Pericardial Bioprosthesis.

Controversy regarding the optimal pulmonary valve substitute remains, with no approved surgical valve for pulmonary valve replacement (PVR). Furthermore, unfavorable anatomy often precludes transcatheter PVR in patients with congenital heart disease. We therefore sought to evaluate the feasibility of the Edwards Inspiris pericardial aortic bioprosthesis in the pulmonary position in pediatric and adult patients requiring PVR. Data from consecutive patients who underwent PVR from February 2019 to February 2021 at our institution were retrospectively reviewed. Postoperative adverse events included paravalvular or transvalvular leak, endocarditis, explant, thromboembolism, valve thrombosis, valve-related bleeding, hemolysis, and structural valve degeneration. Progression of valve gradients was assessed from discharge to 30 days and one year. Of 24 patients with median age of 26 years (interquartile range [IQR]: 17-33; range: 4-60 years), 22 (91.7%) patients had previously undergone tetralogy of Fallot repair and 2 (8.3%) patients had undergone double-outlet right ventricle repair in the neonatal period or infancy. All patients had at least mild right ventricular (RV) dilatation (median RV end-diastolic volume index 161.4, IQR: 152.3-183.5 mL/m2) and at least moderate pulmonary insufficiency (95.8%) or stenosis (8.3%). Median cardiopulmonary bypass and cross-clamp times were 71 (IQR: 63-101) min and 66 (IQR: 60-114) min, respectively. At a median postoperative follow-up of 2.5 years (IQR: 1.4-2.6; range: 1.0-3.0 years), there were no mortalities, valve-related reoperations, or adverse events. Postoperative valve gradients and the severity of pulmonary regurgitation did not change significantly over time. At short-term follow-up, the bioprosthesis in this study demonstrated excellent safety and effectiveness for PVR. Further studies with longer follow-up are warranted.

Case Report of Absent Pulmonary Valve with Intact Interventricular Septum

Abstract Absent pulmonary valve syndrome is a rare cardiac malformation, usually associated with tetralogy of Fallot. Its presence with intact interventricular septum is even less common with case reports or very small series in the literature. We describe a case who presented with symptoms of right heart failure due to an absent pulmonary valve with severe pulmonary regurgitation and small atrial septal defect. Diagnostic evaluation revealed grossly dilated main pulmonary artery and rudimentary leaflets of the pulmonary valve with severe regurgitation. Ventricular septum was intact and there was no patent ductus arteriosus. Later, the patient underwent surgical prosthetic pulmonary valve implantation.

Do we always need a pulmonary valve?

Abstract Limited right ventricular (RV) outflow patching with preservation of pulmonary valve function are key therapeutic goals during primary repair of tetralogy of Fallot (TOF). Obligatory severe pulmonary regurgitation (PR) following the repair of tetralogy has variable consequences. This is the story of a 38-year-old young woman (out of several such cases) whom the corresponding author has followed for 37 years after she was operated upon for complete repair of the TOF at 1 year of age. During surgery, her pulmonary valve was completely removed, leaving just a tag of valvar tissue. Despite severe PR, she has enjoyed an unrestricted childhood, got married, had two children, and remains completely symptom-free till date. She has normal RV function and no heart failure. This raises an important philosophical question about the necessity of an intact pulmonary valve for long-term survival.

Management of tetralogy of Fallot in South Africa

This issue of the Journal contains 2 papers on the local management of tetralogy of Fallot (TOF). The first comprehensively and frankly reviews the surgical repair of TOF in a state hospital. The detailed text is well complemented by excellent tables and figures. Particularly noteworthy is the complete (100%) early postoperative studies of the severity of pulmonary regurgitation, right ventricular outflow gradients and trans-annular plane systolic excursion (TAPSE), by transthoracic echocardiogram. Under the circumstances, the surgery itself was satisfactory.

Five-year follow-up after percutaneous pulmonary valve implantation using the Venus P-valve system for patients with pulmonary regurgitation and an enlarged native right ventricular outflow tract.

Percutaneous pulmonary valve implantation (PPVI) with the self-expandable Venus P-valve system is a promising treatment for patients with pulmonary regurgitation (PR) and a native right ventricular outflow tract (RVOT). However, limited data is available regarding its midterm outcomes. This study assessed the midterm clinical and echocardiographic outcomes following Venus P-valve implantation. From 2013 to 2018, 55 patients with moderate or severe PR after surgical RVOT repair with a transannular or RVOT patch were consecutively enrolled from six hospitals in China. Five-year clinical and echocardiographic outcomes were collected and evaluated. The primary endpoint was a freedom from all-cause mortality and reintervention. At 5 years, the primary endpoint was met for 96% of patients, corresponding to a freedom from all-cause mortality of 96% (95% confidence interval [CI]: 86%-99%) and freedom from reintervention of 98% (95% CI: 87%-100%). Endocarditis was reported in five patients (four patients within 1 year and one patient at 5 years) following PPVI. Transpulmonary gradient and stent orifice diameter remained stable compared to at discharge (p＞0.05). No paravalvular leak was reported while only 1 patient gradually increased to moderate PR during follow-up. Significant improvement of RV diameter and LVEF(p＜0.001) sustained over the 5-year follow-up, in consistent with remarked improved New York Heart Association(NYHA) functional class (p＜0.001). The 5-year results of the China VenusP Study demonstrated the midterm benefits of Venus P-valve implantation in the management of patients with severe PR with an enlarged native RVOT by providing sustained symptomatic and hemodynamic improvement.

The Nakata index and McGoon ratio: correlation with the severity of pulmonary regurgitation after the repair of paediatric tetralogy of Fallot.

Pulmonary regurgitation is the most common complication after the complete repair of tetralogy of Fallot, and severe pulmonary regurgitation after surgery requires pulmonary valve replacement. In this retrospective observational, cross-sectional study, we included a total of 56 children aged 6 years or younger who underwent complete repair of TOF at Shahid Rajaei Cardiovascular Medical and Research Center in Tehran, Iran. Preoperative dual-source computed tomography was used to measure the McGoon ratio and Nakata index. The patients were divided into two groups based on the severity of postoperative pulmonary regurgitation, as estimated by trans-thoracic echocardiography: the severe pulmonary regurgitation group and the non-severe pulmonary regurgitation group. The McGoon ratio and Nakata index were then compared between the two groups. When comparing the two groups, we found that the corrected right pulmonary artery diameter, main pulmonary artery diameter, and McGoon ratio in the non-severe pulmonary regurgitation group were higher than in the severe pulmonary regurgitation group. However, none of these differences were statistically significant. Additionally, other variables, including the corrected left pulmonary artery diameter and Nakata index, showed higher measurements in children with severe pulmonary regurgitation, but again, the differences were not statistically significant. This study indicates that pulmonary arteries diameter, Nakata index, and McGoon ratio were not significantly correlated with the severity of pulmonary regurgitation after the complete repair of tetralogy of Fallot.

Pulmonary Valve Replacement Timing Following Initial Tetralogy of Fallot Repair: A Systematic Review.

Pulmonary valve replacement (PVR) is a critical aspect of surgical management for patients with tetralogy of Fallot (ToF). Determining an optimal timeframe for intervention is imperative, as it directly impacts long-term outcomes and the risk of complications in ToF patients. Ventriculotomy with the transannular patch is currently indicated for right ventricular outflow tract obstruction, but the patch itself can lead to pulmonary regurgitation (PR), dyspnea, and cyanosis, among other complications. This investigation seeks to establish an evidence-based timeline to enhance the overall quality of care for individuals with this congenital heart condition. From 2002 to 2022, 21,935 articles regarding the PVR timing for ToF were examined and filtered. The publications were screened using PRISMA guidelines, and 32 studies were included for analysis and review. Among the studies, PVR was strongly indicated for patients who had developed severe PR, especially in asymptomatic patients and those experiencing fatigue and exercise intolerance. Severe PR was associated with arrhythmias such as right bundle branch block, atrioventricular block, and prolonged QRS intervals, in which male sex and high right ventricular end-diastolic volume (RVEDV) were significant predictors of long preoperative QRS duration. Most physicians found RVEDV necessary for making surgical referrals despite a lack of correlation between PR severity and RVEDV or indexed right ventricular end-systolic volume (RVESVi). However, asymptomatic ToF patients with preoperative RVESVi benefited from PVR. Except for some variations in QRS intervals among studies, arrhythmias tended to persist post-op, yet NYHA functional class and RV size improved significantly following PVR. Older age at PVR was found to be associated with adverse cardiac events, whereas early PVR presented with appropriately short QRS intervals. Cardiac function tended to be significantly worse in patients undergoing late PVR versus early PVR, with timelines ranging from one to three decades following initial ToF repair. Choosing the best timeline for PVR largely depends on the patient's baseline cardiopulmonary presentation, and additional quantitative deformation analysis can help predict an appropriate timeline for ToF patients.

Cardiopulmonary exercise testing in repaired tetralogy of Fallot and supraventricular arrythmias

Abstract Background The arrhythmia burden in adult patients (Ps) with tetralogy of Fallot (TOF) is considerable, being a major late complication in repaired TOF. The incidence of atrial arrhythmias is relatively high and one of the main causes of morbidity. Our aim was to assess which cardiopulmonary exercise testing (CPET) parameters best correlate with supraventricular arrythmias (SVA) to potentially improve identification of high-risk Ps. Methods A single-center retrospective analysis was performed from 2009 to 2018 on adult Ps with repaired TOF who underwent maximal CPET. Ambulatory ECG monitoring was used to analyze the arrhythmic profile. Demographics, standard measures of CPET interpretation, and major cardiovascular outcomes were collected. Multivariate analysis for the prediction of SVA was performed using Cox Regression, by including all statistically significant variables in the univariate analysis and those considered clinically relevant. Results CPET was performed in 63 repaired TOF Ps (57% male, mean age of 34 ± 9 years), with a mean follow-up of 60 ± 33 months. 56% Ps had severe pulmonary regurgitation and 48% Ps underwent pulmonary valve replacement (PVR). Supraventricular arrhythmias occurred in 12 Ps (19%), mainly atrial fibrillation or atrial flutter (67%). There were no statistically significant differences regarding the clinical profile and baseline CPET parameters between both groups, namely: age (p=0.113), male gender proportion (p=0.581), proportion of Ps who underwent PVR (p=0.578), RV systolic dysfunction prevalence (p=0.854) and peak oxygen uptake (p=0.083). VE/VCO2 slope was an independent predictor of SVA (HR 1.41, CI 95% 1.08-1.84, p=0.012). Exercise capacity assessed by estimated metabolic equivalents (METS), as well as the peak heart rate (PHR) during exercise (HR 0.86, CI 95% 0.76-0.96, p=0.007), revealed a protective effect regarding SVA (HR 0.71, CI 95% 0.51-0.98, p=0.045). Neither peak oxygen uptake (p=0.090) nor cardiorespiratory optimal point (p=0.427) showed statistically significant correlation with SVA during follow-up. Ps with a PHR above 165 bpm had a significantly higher survival free of SVA (log-rank p=0.045). Conclusion In our population, VE/VCO2 slope was an independent predictor of SVA during follow-up, while both a higher PHR and a higher exercise capacity had a protective effect. CPET could be an accessible way of improving risk-stratification of TOP Ps and should therefore be included in their routine assessment.

Abstract 13830: Pheochromocytoma in a Patient With Tetralogy of Fallot and Chromosome 17p12 Duplication

Description of Case: A 22-year-old male with Tetralogy of Fallot (TOF) status post transannular patch repair, hypothyroidism, and known partial duplication of chromosome 17p12 concerning for Charcot-Marie-Tooth disease (CMT), presented to his cardiologist with exertional angina and dyspnea, difficulty gaining weight, and diaphoresis. Cardiac MRI demonstrated moderate to severe pulmonic regurgitation with regurgitation fraction of 35% and RV end-diastolic volume index of 150 cc/m 2 . He was referred for pulmonic valve replacement surgery. While awaiting surgical evaluation, he presented to an ER with new hypertension with blood pressure to 240/140 and tachycardia to 107. A CT scan demonstrated a 4.3 x 5.0 x 4.4 cm mass in the right adrenal gland. On admission he was started on phenoxybenzamine and carvedilol. Workup revealed elevated catecholamines and metanephrines ( Table ). He underwent surgical adrenalectomy without complications. Immunohistochemical staining was consistent with pheochromocytoma. Post-procedurally, he was normotensive off medications. He was seen in clinic three weeks after surgery with significant improvement in symptoms. Discussion: We report on a novel genetic association of chromosome 17p12 duplication and pheochromocytoma. The region transcribes peripheral myelin protein-22, which has associations with CMT. Overlap has been demonstrated in other CMT-associated mutations and pheochromocytoma syndromes (e.g. kinesin family member 1B). In congenital heart disease, risk for pheochromocytoma is felt to be driven by hypoxia causing catecholamine secretion, adrenal hyperplasia, and eventual neoplasia. Further study is needed to characterize genetic associations between pheochromocytoma, neuropathy, and congenital heart disease. This patient’s presentation is a lesson in maintaining a high index of suspicion for pheochromocytoma in congenital heart disease, especially with associated genetic syndromes.

Blood biomarkers to detect functional impairment in adult patients with repaired tetralogy of Fallot

BackgroundThe relationship between plasma brain natriuretic peptide (NT-proBNP) and soluble suppression of tumorigenicity-2 (sST2) with structural adaptions and exercise capacity remains incompletely described in patients with repaired Tetralogy of Fallot (rTOF). MethodsPeripheral venous blood samples were drawn for 99 patients with repaired TOF, 59 patients with severe pulmonary regurgitation (PR) and 40 patients with no or mild PR. NT-proBNP was measured using enzyme-linked immunosorbent assays (Roche Diagnostics, Indianapolis, IN). Soluble ST2 levels were assessed on Aspect-plus ST2 quantitative rapid test. ResultsThe mean value of NT-proBNP was 160 ± 137 pg/ml, and sST2 was 29 ± 13, ng/ml in the entire population. 58 % had an elevated NT-proBNP, while sST2 was abnormal in 40 %. Mean NT-proBNP was significantly higher in patients with severe PR (169 ± 150 vs145 ± 118, pg/ml, p < 0.001), while similar sST2 levels were observed in both groups (29 ± 14 vs30 ± 12, ng/ml, p > 0.05). NT-proBNP and sST2 levels were higher in patients with transannular patch when compared to other RVOT intervention (174 ± 145 vs 107 ± 100, pg/ml, p < 0.001); (31 ± 13 vs 29 ± 15, ng/ml, p < 0.05). Both biomarkers were significantly associated with exercise capacity, but NT-proBNP (r = −0.60, p < 0.001) was stronger. The optimal cut-off of 90 pg/ml for NT-proBNP had a sensitivity of 74 % and specificity of 63 % for detection of impaired exercise capacity. ConclusionsSerum levels of sST2 and NT-proBNP are elevated in patients with repaired TOF, with higher values observed in those with severe PR, but also in patients undergoing transannular patch repair. Incorporating both markers in these patients increased the ability to detect impairment in exercise capacity.