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Background: Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia and death have not been identified.Methods: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort (International Multicenter TOF Registry), a 4-center international cohort study, who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Preprocedural clinical, ECG, cardiovascular magnetic resonance, and postoperative outcome data were analyzed. Cox proportional hazards multivariable regression analysis was used to evaluate factors associated with time from pre-PVR cardiovascular magnetic resonance until the primary outcome: death, aborted sudden cardiac death, or sustained ventricular tachycardia.Results: Of the 452 eligible patients (median age at PVR, 25.8 years), 36 (8%) reached the primary outcome (27 deaths, 2 resuscitated death, and 7 sustained ventricular tachycardia) at a median time after PVR of 6.5 years. Cox proportional hazards regression identified pre-PVR right ventricular ejection fraction <40% (hazard ratio, 2.39; 95% CI, 1.18-4.85; P=0.02), right ventricular mass-to-volume ratio ≥0.45 g/mL (hazard ratio, 4.08; 95% CI, 1.57-10.6; P=0.004), and age at PVR ≥28 years (hazard ratio, 3.10; 95% CI, 1.42-6.78; P=0.005) as outcome predictors. In a subgroup analysis of 230 patients with Doppler data, predicted right ventricular systolic pressure ≥40 mm Hg was associated with the primary outcome (hazard ratio, 3.42; 95% CI, 1.09-10.7; P=0.04). Preoperative predictors of a composite secondary outcome, postoperative arrhythmias and heart failure, included older age at PVR, pre-PVR atrial tachyarrhythmias, and a higher left ventricular end-systolic volume index.Conclusions: In this observational investigation of patients with repaired tetralogy of Fallot, an older age at PVR and pre-PVR right ventricular hypertrophy and dysfunction were predictive of a shorter time to postoperative death and sustained ventricular tachycardia. These findings may inform the timing of PVR if confirmed by prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling.Methods: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y).Results: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m2; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m2; P<0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m2 and RVESVi ≤82 mL/m2. RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P<0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm2/m2; P<0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality (P=0.03) over a median of 9.5 years of follow-up.Conclusions: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m2 confers optimal chances of normalization of RV function. [ABSTRACT FROM AUTHOR]

Background: We have previously shown that neonates in profound cardiogenic shock caused by a severe Ebstein anomaly can be successfully salvaged with fenestrated right ventricular exclusion and systemic to pulmonary shunt (modified Starnes procedure). The long-term outcome of single-ventricle management in these patients is not known.Methods: We retrospectively reviewed the records of patients who underwent neonatal Starnes procedure between 1989 and 2015. Patient demographics, clinical variables, and outcome data were collected.Results: Twenty-seven patients (13, 48% boys) underwent the Starnes procedure at 7 (5-9) days of life. All were intubated and on prostaglandin, 24 (89%) were inotrope dependent, and 22 (81%) had no antegrade flow from the right ventricle. Three patients underwent nonfenestrated right ventricular exclusion, 2 (67%) of whom died. Of the remaining 24, 3 (13%) died during the same hospitalization. The 22 neonatal survivors have been followed for 7 (6-8) years: 1 patient is awaiting a Glenn procedure; 1 died after undergoing a Glenn procedure; and the remaining 20 patients have successfully undergone Fontan completion. Their indexed pulmonary vascular resistance was 1.8 (1.2-2.3) W/m2, and mean pulmonary pressure was 12 (9-18) mm Hg. At last follow-up, 1 patient had died, and the remaining patients had normal left ventricular function, and all but 1 have New York Heart Association class I symptoms. Two patients have required pacemaker implantation, whereas the rest are in sinus rhythm. Survival for the entire cohort at 1, 5, and 10 years is 81±4%, 81±5%, and 76±3%, respectively, whereas for those with fenestrated right ventricular exclusion, survival at 1, 5, and 10 years is 87±2%, 87±2%, and 81±4%, respectively.Conclusions: Long-term single-ventricle outcomes among neonatal survivors of the modified Starnes procedure are excellent. There is reliable remodeling of the excluded right ventricle and good function of the left ventricle. [ABSTRACT FROM AUTHOR]

An editorial is presented on the article "Preoperative Predictors of Death and Sustained Ventricular Tachycardia After Pulmonary Valve Replacement in Patients with Repaired Tetralogy of Fallot Enrolled in the INDICATOR Cohort." The authors discuss the results of the study which described preoperative risk factors for postoperative occurrence of death. They suggest the need of more information on the preoperative pathogenesis and postoperative modification of risk factors for poor outcomes.

The article presents several case studies related to health. Topics discussed include the 61-year-old man who presented with decreased exercise capacity, malaise, and pleuritic back pain to an outside emergency department, the right-dominant system showed by the coronary angiography, and the possible observation of the systemic embolization in the right-sided endocarditis.

Background--Studies of transcatheter pulmonary valve (TPV) replacement with the Melody valve have demonstrated good short-term outcomes, but there are no published long-term follow-up data. Methods and Results--The US Investigational Device Exemption trial prospectively enrolled 171 pediatric and adult patients (median age, 19 years) with right ventricular outflow tract conduit obstruction or regurgitation. The 148 patients who received and were discharged with a TPV were followed up annually according to a standardized protocol. During a median follow-up of 4.5 years (range, 0.4-7 years), 32 patients underwent right ventricular outflow tract reintervention for obstruction (n=27, with stent fracture in 22), endocarditis (n=3, 2 with stenosis and 1 with pulmonary regurgitation), or right ventricular dysfunction (n=2). Eleven patients had the TPV explanted as an initial or second reintervention. Five-year freedom from reintervention and explantation was 76±4% and 92±3%, respectively. A conduit prestent and lower discharge right ventricular outflow tract gradient were associated with longer freedom from reintervention. In the 113 patients who were alive and reintervention free, the follow-up gradient (median, 4.5 years after implantation) was unchanged from early post-TPV replacement, and all but 1 patient had mild or less pulmonary regurgitation. Almost all patients were in New York Heart Association class I or II. More severely impaired baseline spirometry was associated with a lower likelihood of improvement in exercise function after TPV replacement. Conclusions--TPV replacement with the Melody valve provided good hemodynamic and clinical outcomes up to 7 years after implantation. Primary valve failure was rare. The main cause of TPV dysfunction was stenosis related to stent fracture, which was uncommon once prestenting became more widely adopted. [ABSTRACT FROM AUTHOR]

The article discusses the case of a female patient with a history of tetralogy of Fallot (TOF). Topics discussed include complete repair of the patient's congenital heart defect when she was still an infant, abnormalities found on electrocardiographic evaluation and cardiopulmonary exercise test, and recommendation for surgical pulmonary valve replacement (PVR).

The author discusses the Ross Procedure for aortic valve replacement (AVR) in young adults. He says that cardiac surgeons have had an uneasy relationship with this method for managing aortic valve disease since the original description of AVR with a pulmonary autograft by Donald Ross in 1967. He adds that the implanted autograft functions normally with no evidence of late deterioration in several patients.

Background--Indications for surgical pulmonary valve replacement (PVR) after repair of tetralogy of Fallot have recently been broadened to include asymptomatic patients. Methods and Results--The outcomes of PVR in adults alter repair of tetralogy of Fallot at a single tertiary center were retrospectively studied. Preoperative cardiopuhnonary exercise testing was included. Mortality was the primary outcome measure. In total, 221 PVRs were performed in 220 patients (130 male patients; median age, 32 years; range, 16-64 years). Homografts were used in 117 patients, xenografts in 103 patients, and a mechanical valve in 1 patient. Early (30-day) mortality was 2%. Overall survival was 97% at 1 year, 96% at 3 years, and 92% at l0 years. Survival after PVR in the later era (2005-2010; n=156) was significantly better compared with survival in the earlier era (1993-2004; n=65; 99% versus 94% at 1 year and 98% versus 92% at 3 years, respectively; P=0.019). Earlier era patients were more symptomatic preoperatively (P=0.036) with a lower preoperative peak oxygen consumption (peak Vo2 P<0.001). Freedom from redo surgical or transcatheter PVR was 98% at 5 years and 96% at l0 years for the whole cohort. Peak Vo2, VE/VCO2 slope (ratio of minute ventilation to carbon dioxide production), and heart rate reserve during cardiopulmonary exercise testing predicted risk of early mortality when analyzed with logistic regression analysis; peak Vo2 emerged as the strongest predictor on multivariable analysis (odds ratio, 0.65 per 1 mL⋅kg-1⋅min-1 P=0.041). Conclusions--PVR after repair of tetralogy of Fallot has a low and improving mortality, with a low need for reintervention. Preoperative cardiopulmonary exercise testing predicts surgical outcome and should therefore be included in the routine assessment of these patients. [ABSTRACT FROM AUTHOR]

The article presents research on the effects of preoperative pulmonary hemodynamics on the residual capacity and lung mechanics during congenital heart surgery. The research observes the lung volume changes and the mechanical properties of the respiratory system in children with either hypoperfused lungs or pulmonary hyperperfusion, and reassessments were done preoperatively. In conclusion, it was observed that volume losses and mechanical deterioration of the lungs, possibly through reduced filling of pulmonary capillaries, were less pronounced in those with pulmonary hyperperfusion than those with hypoperfused lungs.

An introduction is presented in which the editor discusses various reports within the issue on topics including a study on transcatheter aortic valve implantation, the risk for bacterial infection after transcatheter pulmonary valve replacement (TPVR) and the etiology of infectious endocarditis.

The author comments on a study which examined the effect of age on biventricular response in patients with repaired tetralogy of Fallot (TOF) following pulmonary valve replacement (PVR) for right ventricular outflow tract dysfunction. The study is said to have confirmed that increases in age lead to increased frequency of the procedure. The author also describes proposed indications for recommending PVR for similar patients.

The article focuses on cardiac remodeling after surgical pulmonary valve replacement (PVR) in adults. Topics discussed include use of cardiovascular magnetic resonance imaging for the study, imaging revealing that right heart structural reverse remodeling taking place immediately after PVR, risk of adverse outcome linked to sex, age, and etiology of the disease, and volumetric measurements associated with the risk of heart failure.

B Learning Objectives: b The Compensatory Reserve Index (CRI) is a non-invasive technology that uses machine learning to analyze features of pulse waveforms on photoplethysmography. In adults, the CRI trends progression from baseline (CRI = 1) to hemodynamic instability (CRI = 0) more sensitively than changes in mean arterial pressure (MAP). In both T2 and T3, IC CRI remained at a 53% decline whereas RU CRI first nadired in T2 (-35%) then increased in T3 (-26%). [Extracted from the article]

Background: To determine if RV volume was predictive of survival and cardiovascular adverse event (CAE) after pulmonary valve replacement (PVR). Methods: We reviewed the MACHD ( M ayo A dult C ongenital H eart D isease) database for patients with tetralogy of Fallot (TOF) undergoing PVR, 2000-2015. The patients were divided into quartiles based on RV end-diastolic volume index (RVEDVI); those in the lowest quartile (Group A, n=46) and the top quartile (Group B, n=42) were selected as the study cohort. Results: In comparison to Group A, Group B patients were older at time of PVR (28±4 vs 33±5 years, p=0.011) and had larger RV volumes (RVEDVI 127 [117-138] ml/m2 vs 1 91 [179-208], p<0.001; RVESVI 64 [57-73] ml/m2 vs 122 [103-136], p<0.001). A total of 28 CAE occurred in 23 patients during 69 (33-94) months follow-up: death (n=4), heart transplant listing (n=1), initiation of palliative care (n=1), heart failure hospitalization (n=11), stroke (n=2) and sustained ventricular tachycardia/aborted sudden cardiac death (n=9). Survival was similar between Groups A and B (95% vs 91% at 10 years, p=0.273) but freedom from CAE was significantly lower in Group B (67% vs 36% at 10 years, p=0.002). Combination of RVESVI: >95 ml/m2 and tricuspid annular plane systolic excursion/RV systolic pressure (TAPSE/RVSP) <0.4 predicted CAE with sensitivity of 67% and specificity of 92%. Conclusion: Patients undergoing PVR at larger RV volumes had similar survival but more overall CAE. A larger study population with a longer follow-up will be required to determine if early PVR provides survival benefit in the long-term. Key words: Right ventricular volumes; Pulmonary regurgitation; Tetralogy of Fallot; Survival; Cardiovascular adverse events [ABSTRACT FROM AUTHOR]

Introduction: Right ventricular failure (RVF) still occurs in >20% of left ventricular assist device (LVAD) recipients. In this prospective, single-center study, we evaluated the potential of echocardiography to predict 90-day RVF in LVAD recipients. Methods: We performed standard and speckle-tracking echocardiography, with focus on right ventricular (RV) function and mechanics, within 7 days of scheduled LVAD implantation in adults with INTERMACS ≥2 profile, excluding those with planned RV support or pulmonary vascular resistance >6 Wood units. The primary endpoint was RVF by 90 days, defined per INTERMACS 4.0 protocol as elevated central venous pressure (CVP) >16 mmHg and manifestations of elevated CVP accompanied by (1) RVF-related death or mechanical RV support (severe); (2) inotropes or inhaled/IV pulmonary vasodilators any time >7 days post-implant (>14 days: severe; ≤14: moderate); or (3) readmission(s) for RVF (≥2: severe; 1: moderate). Results: Between 7/2012 and 12/2016, 83 patients were enrolled (Table 1). At 90 days, 35 patients (42.2%) developed RVF (22 [26.5%] severe, 13 [15.7%] moderate). Five patients (6.0%) died, 3 from RVF. Median length of stay (LoS) in intensive care was 7 days (6, 10) and total LoS was 15 days (12, 21). Postoperative inotropes were used for 7 days (5, 12) and 14 (16.9%) of patients were readmitted for RVF. Among echo parameters (Table 2), height-indexed inferior vena cava diameter (OR per mm/m 1.24; 95% CI: 1.03-1.49; P=0.025) and pulmonary valve acceleration time (OR per -10ms 1.42; 95% CI: 1.02-1.97; P=0.039) best predicted RVF using best-subset selection. Preoperative pulmonary wedge pressure (OR per mmHg 1.11; 95% CI: 1.03-1.20; P=0.008) was the only independent clinical predictor of RVF. These 3 variables combined had C=0.78 for RVF prediction. RV mechanics did not improve risk assessment. Conclusions: Standard echocardiography helps predict short-term post-LVAD RVF. However, RV mechanics do not improve predictive accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary valve replacement is required for the patients with right ventricular outflow tract (RVOT) dysfunction, surgical and percutaneous pulmonary valve replacement are the treatment options. Percutaneous pulmonary valve implantation (PPVI) provides a less invasive therapy for the patients. The aim of this study was to evaluate the efficacy and safety of PPVI in patients with RVOT dysfunction and the optimal time for implantation. Methods: We searched PubMed, EMBASE, Clinical Trail, Google Scholar until May 2018. The primary efficacy endpoint was the change of mean RVOT gradient, secondary endpoints were the change of pulmonary regurgitation fraction (PRF), left and right ventricular end diastolic and systolic volume index, and left ventricular ejection fraction. The safety endpoints were complication rates. Results: A total of 20 studies with 1246 participants were enrolled, successfully implantation were performed in 1187 patients. There was a significantly decrease in mean RVOT gradient (WMD = -19.63 mmHg, [95%CI, -21.15, -18.11], P=0.002). Right ventricle end-diastolic volume was improved (WMD=-17.59 mL/m2, [95%CI, -20.93, -14.24], P=0.036), but patients with a preoperative indexed RV end-diastolic volume >140 ml/m2 did not reach a normal size (100 mL/m2). Notable decrease was observed in PRF (WMD=-27.3%, [95%CI, -36.16, -18.46], P<0.001). Procedure success rate was 99% [95%CI, 98-99] with a stent fracture rate of 5% [95%CI, 4-6] and pooled infective endocarditis rate was 2% [95%CI, 1-4], incidence of reintervention was 5% [95%CI, 4-6]. Conclusions: In patients with RVOT dysfunction, PPVI can improve ventricular function, provide good hemodynamic and clinical outcomes. To reach a normal RV volume, the study suggests PPVI should be performed before RV end-diastolic volume reaches 140 ml/m2. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Tetralogy of Fallot who had pulmonary valve replacement (PVR) are at risk for prosthetic valve failure that requires repeated valve replacement. Hypothesis: We hypothesize that the pre-operative geometry of the right ventricular outflow tract (RVOT) and the central pulmonary arteries is a predictor of future prosthetic valve dysfunction. Methods: In a retrospective study, using pre-operative cardiac MRI, we measured morphologic parameters including bifurcation angles, length, major and minor diameters, area, and circumference in various locations along the RVOT, pulmonary trunk (PT) and branch pulmonary arteries (BPAs) in 48 patients with Tetralogy of Fallot before they underwent PVR. Physiologic data was collected from their imaging reports (age, weight, height, body surface area (BSA), ventricular volumes and ejection fractions, valvular regurgitant fractions). All measurements were normalized by the patients' BSA. Post-operative pulmonary valve function was assessed using Echocardiograms performed at an average of 5.5 years after the surgery. Valve dysfunction was defined as pulmonary regurgitation and/or pulmonary stenosis of at least moderate intensity. All geometric and physiologic parameters were compared between the group of patients who developed pulmonary valve dysfunction and those who did not, using a two-tailed Student t-test. Results: Patients who developed valve dysfunction had (1) greater RVOT circumference (p=0.038), (2) a more acute bifurcation angle between the PT and the Left Pulmonary Artery (p=0.016), and (3) smaller cross-sectional area at the distal BPAs (p=0.031, p=0.026). Conclusions: A dilated RVOT leading to flow vortices may increase the shear stress experienced by the valve, a sharp bifurcation angle disrupts flow patterns, adding dynamic load to the valve, and stenosis in the distal BPAs lead to increased resistance and an increased volume load to the valve - all promoting valve degeneration. Our findings are consistent with physiologic expectations and will be further explored using computational fluid dynamic simulations to elucidate how the parameters identified impact the hemodynamics around the pulmonary valve. A deeper understanding of the hemodynamic implications may ultimately reduce the incidence of valve degeneration by helping surgeons identify patients who are at high risk for valve dysfunction and guiding them to reconstruct the RVOT in specific configurations. [ABSTRACT FROM AUTHOR]

Introduction: In patients with isolated pulmonary stenosis (iPS), dilatation of the MPA has been reported, sometimes developing into large aneurysms (giantPA). The incidence, aetiology, natural history, and its treatment. Methods: We identified all patients with iPS that attended our tertiary cardiac centre (one of the largest in the UK) between 2003 and 2018 and reviewed clinical notes, echocardiography and MRI data. We evaluated the incidence of MPA dilatation in patients with iPS and its relation to age and pulmonary valve (PV) function. Results: 197 patients (107 children, 90 adults) with iPS were identified. 122 (62%) underwent balloon dilatation of PV for severe stenosis (median age 0.65 IQR 0.08-5.18 years), 30 (15%) underwent PV repair or replacement (median age of 2.06 IQR 0.9-5.2 years) and 45 (22.8%) did not require any procedure. In patients that did not require a procedure, mean peak velocity on echocardiography was 2.55±0.65 m/sec. In patients that required an intervention, the MPA was normal to mildly dilated in most patients (mean z-score +1.2±2.6). In patients who did not undergo any procedure, the size of the MPA was only weakly correlated with age (R2.10 p <.01) and severity of PV stenosis (p <.22). 12 patients (6% of total population) had giantPA (z-score > 4 in children, diameter > 50 mm in adults). Mean size of the largest diameter of the MPA was +5.8±1.9 z-score in children and 59±5 mm in adults. Of these patient 58% had undergone a procedure (mean age 11±14 yrs). Of note, while in the paediatric cohort the MPA size was easily obtained using echocardiography, in only 30% of adult patients the MPA was well visualized and there was a significant error (25±27%) in the provided measurements compared to 3D imaging obtained with MRI. In 7 of 8 adults with giantPA , diagnosis was made only with MRI. Conclusion: In patients with iPS, the incidence of giantPA is not negligible (at least 6%). MPA dilatation does not seem to correlate with PV function thus suggesting an underlying arteriopathy rather than a flow-related aetiology. In adults, MPA size is unreliably assessed using echocardiography. 3D imaging is therefore indicated in adults patients with iPS even in the presence of mild PV dysfunction. Total; word count : 1875 characters Figure 1: No impact of stenosis severity on MPA size in patient who did not undergo PV repair or replacement Figure 2: Aneurysmal dilatation of the MPA in a patient with isolated pulmonary stenosis (in this case mild stenosis). [ABSTRACT FROM AUTHOR]

Introduction: Ross operation provides young adult and pediatric patients a living valve with excellent hemodynamics and no lifelong anticoagulation. However, autograft dilatation is a concern when it leads to aneurysm formation and autograft insufficiency requiring reoperation. Computational simulations of autograft remodeling are potentially effective to predict autograft dilatation, but require zero-pressure geometry and patient-specific material properties for accuracy. Hypothesis: We hypothesized that pulmonary autograft wall stresses estimated from computational simulations using in-vivo imaging would reasonably correlate with the gold standard, wall stresses determined computationally using ex-vivo autograft specimens at zeto-pressure. We recently showed that autograft wall stresses significantly increased immediately after the Ross operation. Our goal was to compare autograft wall stresses based on in-vivo geometry to those based on ex-vivo autografts. Methods: Magnetic resonance imaging (MRI) was obtained in pre-operative Ross patients and used to reconstruct in-vivo autograft geometry. Pre-stress (zero-pressure) geometry was determined. As controls, pulmonary autografts explanted from normal donor hearts underwent micro-computed tomography scans for reconstruction of ex-vivo geometry. Biaxial stretch testing was performed on both intraoperative tissue from Ross patients and on ex-vivo autografts to determine patient-specific material properties. Finite element simulations using LS-DYNA were performed to determine wall stresses. Results: Imaging from ex-vivo pulmonary autografts (n=6) and Ross patients (n=6) were obtained. Peak stresses were 93 kPa for ex-vivo vs. 113 kPa for in-vivo autografts at 25mmHg and 448kPa vs. 558 kPa, respectively at 120mmHg. Conclusions: Wall stresses at pulmonary and systemic systolic pressure predicted by in-vivo MRI imaging reasonably correlated with wall stresses based upon ex-vivo autograft tissue. Computational simulations using in-vivo imaging provides a suitable surrogate for the gold standard simulations using ex-vivo tissue specimens and broadens clinical applicability of computational simulations for patient-specific outcomes. [ABSTRACT FROM AUTHOR]

Background: Ventricular arrhythmia and sudden death are important late sequelae for patients with Tetralogy of Fallot (TOF). Pulmonary valve replacement (PVR) mitigates but does not eliminate this risk. Appropriate risk stratification of patients with arrhythmic symptoms is therefore an important undertaking. Aim: To define the arrhythmic and survival outcomes in TOF patients following the use of a robust ventricular stimulation protocol combined with surgical ventricular tachycardia (VT) cryoablation at the time of PVR. Methods: A single centre retrospective study of patients with TOF and a clinical indication for PVR who underwent a diagnostic electrophysiology (EP) study prior to surgery if there was a clinical suspicion of VT, between 1988 and 2017. The ventricular stimulation study protocol for TOF patients at our centre uses 2 drive trains (S1 600 and 400, with 5 extra stimuli down to the VERP or 200ms). Surgical cryoablation was performed by one highly experienced operator. Results: 49 patients (mean age 36 ± 11 years) underwent an EP study prior to surgery of which 22 (47.8%) were positive. During PVR, surgical cryoablation was performed in 31 patients. A risk-stratification EP study following surgery was performed in 27 patients. It was positive in 12 (44.4%) of which 2 already had an ICD, 5 received an ICD and 5 did not receive an ICD. A total of 16 (32.6%) patients had an ICD post surgery. At 6 months follow up, there were similar rates of patients with >10% ventricular premature beats (7.7%) and non-sustained VT (27.5%) compared to prior to surgery. At a median follow-up of 8.3 years (IQR: 1-16 years) however, only 3 patients had sustained VT. Two of these patients had an ICD at the time of the event while one did not. All 3 of these patients had a positive EP study following surgery. There was no cardiac mortality. Conclusion: A robust VT stimulation protocol with up to 5 extra stimuli should be considered in high risk TOF patients prior to and after PVR with surgical cryoablation, for appropriate risk stratification. Surgical cryoablation at the time of PVR is an easy and effective means of reducing arrhythmogenic substrate in TOF patients. These two strategies in combination may be associated with a reduction in ventricular arrhythmias and sudden death. [ABSTRACT FROM AUTHOR]

Introduction: In situ tissue engineering (TE) of heart valves uses readily available acellular synthetic biodegradable scaffolds that transform in vivo in autologous living valves. This study hypothesized that scaffold fiber orientation that resembles native collagen alignment (i.e. anisotropic) results in superior valve function, mechanical properties, and matrix formation during in situ TE. Methods: Trileaflet heart valve scaffolds of biodegradable ureidopyrimidinone (UPy)-polymers with anisotropic (n=10; fibers in circumferential direction) or isotropic (n=10) fiber orientation were produced and implanted in the pulmonary position in sheep. Functional evaluation with echocardiography was performed. Explants (1, 6 and 12 months) were analyzed to evaluate cellularity, extracellular matrix formation and organization, and mechanical properties Results: Seventeen animals survived the entire follow-up time and showed functional valves. Consistently higher-pressure gradients were observed for valves in the anisotropic group (not significant at 12 months). Macroscopic analysis revealed pliable leaflets, with no evident differences between the groups. In both groups, fiber resorption was not completed after 12 months and most pronounced at the cell-rich base. Matrix organization did not show apparent differences between the groups, nor in quantity nor in orientation. Notably, anisotropic valves were stiffer in circumferential direction prior to implantation, which already was negated after 1 month of implantation. Conclusions: In situ TE of pulmonary valves demonstrated sustained functionality up to 12 months. Surprisingly, the predefined scaffold fiber organization did not result in significant differences in the newly formed matrix orientation. Apparently, other cues seem to overrule the effect of predefined fiber organization, limiting our possibilities to guide matrix formation by changing scaffold fiber orientation. [ABSTRACT FROM AUTHOR]

Introduction: Right ventricular (RV) pressure and volume loading lead to RV failure but their impact on regional RV work and injury are poorly characterized. Methods: Eight Sugen/hypoxia pulmonary hypertension (PH), 6 pulmonary regurgitation (PR) and 5 sham-control rats were studied. Six (n=4) or 9 wks (n=4) after Su/hy & 12 wks after PR surgery, myocardial strain (speckle tracking echo) and RV pressure (conductance catheter) were measured and RV pressure-strain loops generated. Regional myocardial work was calculated as the pressure-strain loop area (mmHg·%). Regional myocardial work efficiency was quantified as wasted work: ratio of systolic lengthening (wasted) work to shortening work. RV fibrosis (% collagen area) was quantified by picrosirius red stain. Echo derived RV dimensions & fractional area change (FAC%) quantified RV remodeling & function. Results: Peak strain was lower in the PH septum (-12±3, p=0.002) and higher in the PR lateral wall (-28±8%, p=0.02) vs shams (-18±5%). RV lateral wall work was higher in PH vs shams (796±315 vs 373±157mmHg·%, p<0.001), while septal work was similar. In PR, lateral & septal work were higher vs shams (797± 288 mmHg·%, p<0.001 & 549±282 mmHg·%, p=0.03, respectively). But, wasted work was increased only in the PH septum (0.31±0.24 vs 0.08±0.05, p<0.001). PH & PR induced similar RV remodeling (end diastolic area (8.2±1.7 vs 9.8±1 cm2/m2, p=ns); but fibrosis in the lateral wall, but not septum, was higher (9.8±3.0 vs 5.9±0.7%, p < 0.001) and FAC% lower (22± 6 vs 46 ± 10, p < 0.001) in PH vs PR. A linear relation was observed between RV fibrosis burden and regional myocardial work (r=0.62, p<0.001). Conclusions: Asymmetrical RV work and wasted septal work are associated with RV remodeling, dysfunction and fibrosis in experimental PH vs PR. These results provide new insights and quantitative indices to diagnosis RV failure. [ABSTRACT FROM AUTHOR]

Background: Limitations of traditional 2D cardiac MRI (2D CMR) are breath holding and long exam times. 3D time-resolved flow (4DF) MRI is a 5-10 minute, free-breathing, single-sequence exam that simultaneously collects magnitude and phase contrast data. Our primary objective is to compare the precision of gadobenate dimeglumine enhanced 4DF CMR obtained on a 1.5-T MRI with 2D CMR in patients with repaired tetralogy of Fallot (rTOF) to measure pulmonary net flow (PNF), sum of forward flow (FF) and regurgitant flow. Secondary objectives were to compare agreements for ventricular size and function. Methods: Via a retrospective case control study design, a blinded observer segmented 2D and 4DF images from rTOF patients (n=34). For 2D CMR, ventricular volume and function were measured on short-axis SSFP images and flow on phase contrast images at the aortic (AoV) and pulmonary valve (PV). For 4D CMR, ventricular volume and function were measured on simulated short axis acquisitions. Flow measurements were made at the AoV, PV, main pulmonary artery (MPA), and branch pulmonary arteries (BPA). Results: Assessment of PNF using 4DF at the PV demonstrated the strongest correlation (r=0.87) and lowest mean difference (3.5 ± 9.4 ml/beat) to aortic net flow. FF and stroke volume correlated moderately-strongly with 4DF (r=0.68-0.80, p<0.001) and 2D acquisitions (r=0.79-0.81, p<0.001) with no significant difference in correlation coefficients (Fisher's transformation, p>0.12) or mean differences (p>0.24) between techniques. Comparison of 2DF and 4DF ventricular volume measurements demonstrated strong correlations (r=0.75-0.96) and ejection fraction demonstrated moderate correlation (r=0.60-0.75). Right ventricular (RV) volumetry by 4DF demonstrated strong correlation (r=0.95-0.96) with 2D SSFP, but overestimated values (11.8-19.2 mL/beat). Average time to complete 2D CMR was 71.2 ± 18.8 minutes vs. 9.2 ± 1.3 for 4DF acquisitions (p<0.001). Conclusions: In patients with rTOF, 4DF CMR obtained using commonly available techniques is comparably precise to 2D CMR for evaluation of PNF and ventricular volumes with slight overestimation of RV volumes. When RV systolic function is normal on echo, 4DF may be considered as a stand-alone sequence for interval assessments. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with structural and functional changes in the heart. The contributions of metabolic syndrome and obesity to pulmonary hypertension and right ventricular (RV) dysfunction in children remain unclear. To clarify this, we examined the relationships between numbers of cardiovascular risk factors and pulmonary arterial (PA) and RV hemodynamics in obese children. Methods: Echocardiography with tissue Doppler imaging was performed in 345 aged from 6 to 13 years. RV dimensions, isovolumic relaxation time, and tissue Doppler-derived myocardial performance index (MPI) were measured. To measure PA pulse wave velocity (PWV), pulsed Doppler flow wave transmission time (T) between main PA proximal (pulmonary valve) and distal point (PA bifurcation) were measured. The distance (D) from the pulsed Doppler sample volume in the pulmonary valve to the PA bifurcation was measured. The PAPWV was defined as T/D. PA systolic pressure (SP) was calculated by use of the modified Bernoulli equation. Lipids, fasting glucose, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were also assessed. Subjects were divided into 4 groups: A group, waist circumference (WC) within normal range; B group, increased WC; C group, increased WC plus any one of the following individual factors of hypertension, dyslipidemia (low high-density lipoprotein-cholesterol and/or high triglyceride), and raised fasting glucose; D group, metabolic syndrome. Results: With increasing number of metabolic syndrome disorders, PASP and PAPWV increased significantly (Figure). RVMPI was significantly greater in the group D than in the group A,B, and C (Figure). There were significant relationships between PASP and HOMA-IR, triglycerides, uric acid (r = 0.22, 0.24, and 0.20, respectively, p < 0.05). PASP correlated significantly with PAPWV (r = 0.55, p < 0.01) and RVMPI (r = -0.17, p < 0.05). Conclusions: Pulmonary arterial hypertension and pulmonary vascular stiffening become apparent with increasing number of metabolic syndrome disorders. Reduced right ventricular function is associated with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: Repair of tetralogy of Fallot (TOF) during infancy limits the duration of time that the right ventricular volume and pressure are elevated. Whether early TOF repair benefits the right ventricle over the long-term, particularly after pulmonary valve replacement (PVR) as an older child or adult, is unknown. We hypothesized that repair of TOF during infancy (age ≤ 1 year) would result in improved outcomes when PVR is required later in life. Methods: Patients with repaired TOF who subsequently required PVR were identified. Echocardiography assessed the pre-operative, early post-operative (1-3 year), and most recent right ventricular end diastolic diameter (RVEDD). Cardiac magnetic resonance studies quantified the right ventricular end diastolic volume index (RVEDVI). The incidence of ventricular arrhythmias was recorded from Holter monitor testing. Results: Of 79 patients with TOF, 27 were repaired during infancy and 52 after infancy. PVR was performed in all patients 31.1 ± 13.3 years following initial repair. At the time of PVR, there were no significant differences in RVEDD (4.7 ± 1.3 vs. 4.9 ± 1.3 cm; p=0.5) or RVEDVI (181.6 ± 51.0 vs. 180.5 ± 50.8; p= 0.9) between groups. Significant improvements in the RVEDD were observed in both groups from early and most recent echocardiograms. Although the early post-PVR RVEDD was not significantly different between groups, recent follow up at 8.5 ± 4.0 years demonstrated a significant advantage in patients who had TOF repair during infancy (3.5 ± 0.8 vs. 4.2 ± 0.9 cm; p=0.04). In addition, the incidence of ventricular arrhythmias after PVR was higher in children with TOF repaired after infancy (0 vs. 15.3%; p= 0.046). Conclusions: These data suggest sustained benefit, even after PVR, when TOF is repaired during infancy. [ABSTRACT FROM AUTHOR]

Introduction: Tricuspid regurgitation (TR) is a common long-term complication in patients with repaired tetralogy of Fallot (TOF). However, tricuspid valve repair associated to pulmonary valve replacement (PVR) in adults with repaired TOF, is still debated. Hypothesis: We hypothesized tricuspid regurgitation after PVR may affect hepatic and cardiac function. Methods: We performed a retrospective review of patients (n=59) after TOF repair who underwent first PVR with tricuspid valve repair (n=11, Group T) or without tricuspid valve repair (n=48, Group P). Preoperative and postoperative serial echocardiograms and cardiac magnetic resonance (CMR) imaging were assessed for TR, pulmonary regurgitation (PR), right ventricular size and function. Laboratory value were also examined. PR and TR were scored as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Results: Mean follow-up duration was 4.6±3.9 years. Mean age at PVR was 30.8±10.3 years. At 1 year after PVR, there were significant reductions in TR (mean 2.1 vs 0.8, p<0.01) in Group T, in right ventricular end-diastolic volume index and in PR fraction in both groups. At latest follow-up (mean 5.7±3.8years), despite the degrees of PR (mean 0.75 vs 0.8) and pulmonary stenosis (peak pressure gradient 23.1mmHg vs 23.3mmHg) were unchanged in both groups, the degree of TR significantly deteriorated compared with the value 1 year after PVR in Group T (mean 0.8 vs 1.6). At latest laboratory value (mean 5.2±3.5 years), γ-glutamyl transferase was significantly higher in Group T (mean 56 vs 25U/L, p=0.01), platelet count (mean 16.3 vs 20.9 X103/μL, p=0.02) and cholinesterase (mean 274 vs 331U/L, p=0.04) were significantly lower in Group T. In addition, plasma BNP level was significantly higher in Group T (mean 62.9 vs 35.8 pg/ml, p=0.03), Conclusions: Early improvement in TR showed gradual return toward preoperative value in mid-term after PVR and tricuspid valve repair even though pulmonary valve function remains normal. This may suggest TR is due to not only functional regurgitation but structural deformity of tricuspid valve. In addition, our data demonstrated TR might contribute to chronic hepatic and cardiac damage. These findings highlighted the importance of TR after PVR in repaired TOF. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary valve (PV) regurgitation (PR) is common after intervention for TOF and congenital PV stenosis. Secondary PV repair is an alternative to replacement (PVR), but selection criteria are not established. We sought to elucidate preoperative variables associated with successful PV repair and to compare outcomes between repair and PVR. Methods: All patients who underwent surgery for secondary PR from 2010-17 by a single surgeon were studied, excluding those with prior PVR or valvectomy. Feasibility for PV repair was considered preoperatively and determined intraoperatively. PV z-score and total leaflet tissue length were measured by TTE. PV leaflet and annulus areas were measured by MRI. The primary predictor variable was leaflet area indexed to ideal PV annulus area (iLA). All measurements and PR grading were performed offline by 2 authors as per published guidelines. PV repair and PVR groups were compared using univariate analyses (Table) and multivariable logistic regression. Results: Of 85 subjects, 31 (36%) underwent PV repair. Adjusting for age and leaflet thickness, preoperative longer PV total leaflet length (cm/m2) (ß=2.8, p<0.01), larger PV z-score (ß=1.6, p<0.01), and larger iLA (ß=8.5, p<0.01) were associated with successful repair. iLA effectively discriminated between groups by ROC analysis (AUC=0.93, p<0.01). iLA of 0.90 was 91% sensitive and 83% specific for achieving PV repair. Follow up data were available in 68 (80%) subjects at a median 4.3 years. PV reintervention was performed in 7% and 0% of PVR and repair subjects, respectively (log rank p=0.17). Moderate or severe PR was present at most recent follow up in 35% of PVR and 4% of repair subjects (log rank p=0.02). No subjects had significant PV stenosis. Conclusions: At midterm follow up, PV repair was associated with fewer reinterventions and lower likelihood of significant PR than PVR. Preoperative measures indicating more leaflet tissue were associated with successful repair. [ABSTRACT FROM AUTHOR]

Introduction: Survival in patients with Tetralogy of Fallot (TOF) as well as pulmonary atresia with ventricular septal defect (PA/VSD) has significantly increased in the last decades. Data regarding older populations are scarce. Hypothesis: Pat. with TOF or PA/VSD over 40 years are often described as survivors with the assumption of low morbidity. Nevertheless, we assume that this cohort suffers from significant morbidity. Methods: Retrospective cohort study including all pat. at our center who were ≥40 years of age at any point between January 2005 and March 2018 with the diagnosis of TOF or PA/VSD. Time-point of inclusion was the date of the 40th birthday or the first visit after the year 2005 if a patient was already 40 years old in the year 2005. Demographic data, as well as information on medical/surgical history were retrieved from hospital records. Results: Altogether, 184 pat. (58.7% female) with TOF (n= 159) or PA/VSD (n=25) with a mean age of 45.3 ± 7.2 years were included. Out of these 180 (97.8%) had cardiac surgery - 168 pat. (91.3%) corrective, 12 (6.7%) palliative. Pulmonary valve replacement was performed in 66 (35.9%) pat. Mean NYHA class was 1.9 ± 0.9. A pacer or ICD was implanted in 25 pat. (13.6%), while arrhythmias were present in 33 pat. (17.9%). Right ventricular function was impaired in 33 pat. (17.9%) and left ventricular function in 12 pat. (6.5%). Pulmonary hypertension was present in 14 pat. (7.6%). In 78 (42.4%) at least one catheter intervention was performed after the 40th birthday, while 48 pat. (26.1%) underwent their first electrophysiological study after 40. Regarding co-morbidities, arterial hypertension was present in 33 pat. (17.9%) and diabetes in 10 (5.4%). In 13 pat. (7,1%) a cerebrovascular accident occurred. In 28 pat. (15.2%) a thyroid disorder was present. While in 25 pat. (13.6%) a gastro-intestinal disorder was present, renal dysfunction was seen in 21 pat. (11.4%), liver disease in 40 pat. (21.7%), and lung disease in 30 pat. (16.3%). Depression was present in 16 pat. (8.7%), and 7 pat. (3.8%) suffered from cancer. Conclusions: Significant morbidity is present in pat. with TOF or PA/VSD over the age of 40 years with a significant proportion of acquired co-morbidities, and a subsequent high utilization of healthcare resources. [ABSTRACT FROM AUTHOR]

Introduction: Tetralogy of Fallot (TOF) accounts for 10% of congenital heart disease (CHD) and is an important cause of adverse right ventricular (RV) remodeling requiring surgical re-interventions. Clinical predictors of adverse RV remodeling are imprecise. Hypothesis: Genomic factors may predispose to adverse RV remodeling. Methods and Results: We performed whole genome sequencing in 513 non-syndromic surgically repaired TOF patients negative for 22q11del. Using an ACMG pipeline for variant interpretation, we identified pathogenic single nucleotide variants and copy number variants in genes involved in cardiac development, CHD and other cardiac disorders in 27.1% of the cohort. In a nested case-control analysis, we evaluated the association of rare and low-frequency protein-altering variants with risk of adverse RV remodeling using gene collapsing analysis and conducted a pathway enrichment analysis (Gene Set Enrichment Analysis). We defined cases as those with moderate/severe RV dysfunction/dilatation on cardiac imaging and/or requiring pulmonary valve replacement (PVR) (n=294), and controls as those with no/mild RV dilatation/dysfunction and no PVR (n=204). The analysis was adjusted for age at repair, age at last follow-up, sex, ethnicity, and transannular patch. The median age at TOF repair was 16 months (range:6-44), and the median age at PVR (n=159) was 24 years (range:16-38). Freedom from adverse RV remodeling was 87.4% (95% CI:83.7-90.2) and 57.3% (95% CI: 52.0-62.2) at 10 and 20 years respectively. Twenty-three genes were differentially enriched for potentially deleterious variants between cases and controls (p<0.001). Genes associated with cytoskeleton organization, inflammation, fatty acid metabolism were enriched for variants in cases. Genes involved in apoptosis signalling and growth processes were enriched for variants in controls. Conclusion: Whole genome sequencing identified pathways that contribute to adverse RV remodeling in TOF as well as pathways that are protective in TOF. Knowledge of genetic susceptibility may inform management strategies to preserve RV function in at risk patients as well as provide new pharmacological targets for developing drugs to promote RV adaptation. [ABSTRACT FROM AUTHOR]

The article presents abstracts on clinical studies including detection and treatment of anthracycline cardiotoxicity in heart failure patients, outcomes of transcatheter pulmonary valve replacement and role of gender difference in the recovery of patients with acute myocardial infraction.

A letter to the editor is presented in response to articles in previous issues about the medical outcomes of transcatheter pulmonary valve replacement and transcatheter valve replacement in children.