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Introduction: We aimed to determine predictors of reintervention after pulmonary valve replacement (PVR) at our center with the novel consideration of valve angulation within the outflow tract. Methods: Patients with a history of PVR between 06/2007 and 06/2019 and subsequent cardiac catheterization, cardiac MRI, or chest CTA since PVR were eligible for inclusion, as stored images allowed for valve angle measurement. The angle relative to the patient’s anterior-posterior (horizontal) plane was measured using lateral angiography and sagittal cross-sectional images. Valve orientation was analyzed as follows: 1.) the measured angle, 2.) the difference in that angle from the mean of 40 control patients, and 3.) whether that angle was outside of 2 standard deviations from the mean. Other variables included: original cardiac anatomy, valve type, true internal valve diameter indexed for weight at PVR, and immediate post-operative peak systolic gradient and valve insufficiency. Freedom from reintervention was evaluated using the log-rank test and Cox proportional-hazards with multiple imputation of modest missing echocardiographic data. Results: Of 168 patients who underwent PVR during that period, 52 patients met inclusion criteria. Over a median follow-up time of 6.0 years (bootstrapped 95% CI [4.6, 7.4]), 14 of those 52 (26.9%) underwent reintervention (valvuloplasty or valve replacement). In both univariate analysis as well as bivariate analysis controlling for indexed valve diameter, no measure of valve orientation was associated with freedom from reintervention. Potential associations of valve type with the outcome disappeared in bivariate analysis. Higher internal valve diameter indexed for weight at PVR was consistently associated with earlier reintervention. Results for freedom from valve revision were similar to those for any reintervention, while acknowledging that we may be underpowered to detect certain associations. Conclusions: Valve orientation does not appear to impact freedom from reintervention following PVR; however, higher indexed internal valve diameter is associated with decreased time to reintervention. An augmented sample size through multicenter collaboration may allow for a more robust multivariate analysis.

Introduction: Handmade polytetrafluoroethylene (PTFE) conduits have similar durability and efficacy compared to commercially available conduits and homografts used for pulmonary valve replacement (PVR) in pediatric right ventricular outflow tract (RVOT) reconstruction. We evaluated the costs related to use of the PTFE conduits compared to commercial grafts. Hypothesis: When compared to commercial grafts in first-time RVOT reconstruction, PTFE conduits have reduced surgical day costs with similar overall hospital costs per day of conduit life. Methods: Data was collected via retrospective chart review of patients < 2 years of age who underwent first-time PVR from 1/2010 - 3/2019. Initial procedure, all day-of-surgery, and subsequent reintervention costs and charges were examined. Patients were followed until conduit explant, patient death, or 3/2020 (whichever came first) and were adjusted to 2020 USD. Results: Of 52 instances of PVR in RVOT reconstruction, 36 (69%) of grafts were PTFE, and 16 (31%) were commercial. There were no statistically significant differences in gestational age; birth weight; weight, height, or age at intervention; hospital or intensive care unit length of stay; conduit life; or bypass, cross-clamp, or intubation duration between the groups. Compared to commercial grafts, PTFE conduits were associated with lower day-of-surgery hospital charge, day-of-surgery estimated cost, and graft/conduit charge. There was a trend toward lower aggregate cost over conduit life (Table). Aggregate cost per day of conduit life was similar between groups ( p = 0.26). Conclusions: In first-time PVR, PTFE conduits have lower initial and reintervention costs compared to commercially available conduits and homografts. In centers with expertise in handmade conduits, these may provide a less expensive alternative to commercial grafts in pediatric patients requiring RVOT reconstruction.

Introduction: Tetralogy of Fallot (ToF) typically requires surgical repair of the right ventricular outflow tract (RVOT) and subsequent placement of an artificial pulmonary valve. Bioprosthetic valve longevity is highly variable and there is currently little understanding of what hemodynamic factors may lead to early valve dysfunction. Hypothesis: We hypothesize that cardiac output and valve orientation impact the performance of bioprosthetic valves by affecting blood flow patterns in the RVOT. Methods: We analyzed hemodynamics in a 3D printed ToF anatomy model in a physiological flow loop. A 25mm surgical valve was implanted in the model at two orientations: native and rotated 180 degrees. Full 3D, three-component, phase-averaged velocity fields were obtained over the cardiac cycle using 4D flow MRI at cardiac outputs of 2, 3.5, and 5 L/min. We acquired images of valve leaflet motion at 1500Hz. The 4D flow MRI and high-speed camera experiments were run identically, allowing us to examine the relationship between flow fields and leaflet motion. Results: The full velocity fields from the MRI scans revealed key differences among cases in flow features including location of reverse flow regions, systolic jet shape, and asymmetry local to the valve. At 2 L/min, the forward flow through the jet was more asymmetric compared to the other cases and a strong vortex formed, indicating a region of recirculation. With the rotated valve orientation, the 2 L/min case also produced a unique pattern as flow was washed from the RVOT inner curve back toward the center of the valve (Fig 1). Leaflet behavior during systole varied with cardiac output as well, as higher frequency flutter was observed at 5 L/min and the effective valve orifice area was decreased by 8.5% at 2 L/min compared to 5 L/min. Conclusions: We observed key differences in flow patterns and leaflet motion due to cardiac output and valve orientation that could impact leaflet loading and fatigue and long-term valve function.

Introduction: Transcatheter pulmonary valve implantation (TPVi) is a widely available option to treat right ventricular outflow tract (RVOT) conduits, but coronary artery compression is an absolute contraindication. Cardiac magnetic resonance (CMR) may evaluate coronary anatomy, but its utility in predicting coronary compression is not well established. Hypothesis: CMR prior to TPVi can accurately predict coronary compression risk. Methods: We analyzed all patients with a recent CMR (≤ 12 months) and attempted TPVi in an RVOT conduit at 9 centers from 2007-2016. A core lab reviewed all CMRs for the shortest orthogonal distance from a coronary artery to the conduit, the shortest distance from a coronary artery to the most stenotic area of the conduit, and subjective assessment of coronary compression risk. Receiver operating characteristic curve was used to determine optimal predictive distances. Univariate and independent associations of the distances and qualitative assessment with coronary compression were examined using logistic regression. Results: Of 231 patients (62% male, median age 19.0 years), TPVi was successful in 198 (86%); in 24 (10%) balloon testing (documented coronary compression or high risk) precluded implantation. Distance to the RV to PA conduit ≤ 2.1 mm (area under the curve [AUC] 0.70) and distance to most stenotic area ≤ 13.1 mm (AUC 0.69) predicted coronary compression (Table). Subjective assessment had the highest AUC (0.78), with 96% negative predictive value. Both distances and qualitative assessment remained independently associated with coronary compression when controlling for abnormal coronary anatomy. Conclusions: CMR can predict the risk of coronary compression during TPVi in RVOT conduits but cannot completely exclude the risk of coronary compression. CMR may assist in patient selection and counselling families prior to TPVi, although balloon testing prior to TPVi remains essential.

Introduction: Gemella morbillorum is a facultative anaerobic gram positive bacterium that resides as normal flora in the oral cavity and gastrointestinal system. This organism has uncommonly presented as an etiology of infective endocarditis, with varying reports of resistance and complications. Methods: Transparent Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for the systematic review. A medical librarian (T.R.S) versed in evidence-based medicine systematically searched databases for studies assessing Gemella morbillorum infective endocarditis in patients. Publication year included inception until December 31, 2019. Using Rayyan software, 134 abstracts were screened for eligibility after duplicates were removed. Inclusion criteria was age greater than 18 years old, infective endocarditis with positive culture for Gemella morbillorum, and publication in English. 39 full text articles were reviewed for eligibility, and 38 were included in the final analysis. Results: A total of 40 cases of infective endocarditis caused by Gemella morbillorum were identified. The average age of the patients was 54 years old, 72.5% were male patients (29), 20% female (8), 7.5% unknown sex (3). Native valve endocarditis (NVE) was present in 28 of the cases, with prosthetic valve involvement in 5 cases. Left sided endocarditis was more common than right sided with 70% of cases (28) and 12.5% (5) respectively, with 17.5% (7) of cases not listing which valve was infected on echocardiography. The most common predisposing risk factor was thought to be poor dentition in 9 cases. The most common antibiotic regimen in penicillin susceptible NVE was concordant with most recent guidelines, a beta lactam with gentamicin or vancomycin in 57.5% of the cases (23). Complications occurred in 65% of cases (26), with most common complication being need for surgical intervention occurring in 30% of the cases (12). Conclusions: Gemella morbillorum infective endocarditis cases reported in literature had a high burden of complications with nearly two thirds of cases. Most common was the need for surgery with valve replacement. Antibiotic regimens in the most recent endocarditis guidelines were effective in treatment for a majority of the cases.

Introduction: This prospective, multicenter, single-arm, early feasibility study evaluates the safety and performance of an investigational ePTFE-based valve for replacement of the pulmonary valve and reconstruction of the Right Ventricular Outflow Tract. A novel polymeric pulmonary valved conduit, resistant to calcification and structural valve deterioration, may provide a more durable therapy option for the pediatric population by preventing loss of right ventricular function and increased freedom from valve-related reintervention and mortality. Methods: The primary endpoints at 6 months adjudicated by an independent Clinical Events Committee are valve-related mortality and device-related reintervention. The investigational device is a valved conduit comprised of ePTFE with stretch technology and a flexible tri-leaflet polymeric valve made of an advanced proprietary composite material, which can be tailored to length requirements of the anatomy. All enrolled patients met study inclusion/exclusion criteria and had a signed informed consent form. All patients had pre- and postoperative evaluation via transthoracic echocardiography (TTE). Aspirin was administered for a minimum of three months post procedure and, per institutional protocols, four patients were on temporary Coumadin. Results: Of the 17 patients enrolled from three sites, 52.9% were male. Ages ranged from 6 to 17 years (mean 11.5 ± 3.7). BSA ranged from 0.82 to 1.57 m 2 . At six months follow up, 100% of subjects successfully met the primary endpoint of freedom from valve-related mortality and device-related reintervention. No patient exhibited an RVOT gradient > 20 mmHg. No patients had pulmonary regurgitation above baseline (≤ mild) observed through six months. Throughout postoperative serial TTE evaluation at discharge, 1, 3, and 6 months, no evidence of worsening valvular insufficiency was observed. No patient developed endocarditis and TTE detected no clinically significant thrombus formation. Conclusions: These preliminary data of a novel Pulmonary Valve Conduit suggest improved pulmonic and right ventricular function based on TTE measurements, no unexpected findings, no valve-related adverse events and encouraging hemodynamic performance through 6 months.

Introduction: Maternal exposure to various pathogens during pregnancy has been well established as a cause of congenital heart defects (CHD). Suggestive, although inconclusive, data exists of an association between Coxsackievirus B (CVB) infection during pregnancy and CHD. Therefore, this study was undertaken to examine association between perinatal infection with CVB and CHD. Hypothesis: CVB infection during pregnancy may play a role in the pathogenesis of CHD. Methods: In a prospective study of 122 pregnant women with pregnancies affected with CHD, circulating CVB IgG and IgM antibodies in the maternal serum were quantified. To determine specific CVB serotypes involved, Neutralizing antibodies (NA) were measured against three CVB serotypes: CVB1-Chi07, CVB3, Nancy, and CVB4, J.V.B. Results: A significant number of the women were positive for CVB antibodies; 31.1% for IgG and 6.6% for IgM. Elevated levels of IgG were seen in 50% of women carrying babies with Pulmonary Atresia (PA) (p=0.04). In addition, 55.6% (p=0.100) of moms carrying babies with Hypoplastic Left Heart Syndrome (HLHS), aortic atresia/mitral stenosis (AA/MS) variant and 47.1% (p=0.127) of HLHS AA/mitral atresia (MA) had positive IgG levels. Among babies of women with positive IgM titers, 75% (p=0.001) had isolated Ventricular Septal Defect (VSD), comprising 26.1% (6/23) of all babies with isolated VSD in the cohort.We also show a possible association between CVB4 and CHD in the cohort. All mothers with positive IgM titers whose babies were born with a VSD had elevated CVB4 NA (p=0.001). Among women with elevated IgG having babies with PA, 40.0% (p=0.061) had elevated CVB1 NA, 70.0% (p=0.014) had elevated CVB3 NA, and 40.0% (p=0.876) had elevated CVB4 NA. Conclusion: We present data from a clinical study suggesting that CVB infection during pregnancy may contribute to the burden of CHD in affected babies. Our data demonstrates not only an association of CVB with CHD in pregnant women but this is the first report showing significant association between in-utero CVB infection and PA. Our study has broad implications for the future understanding and potential management of CHD as well as introduces a new avenue of research for cardiac defects.

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.

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 propertiesResults: 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.

We thank the authors for their interest in our recent publication in which we reported on significant right heart structural reverse remodeling seen in the immediate postsurgical pulmonary valve replacement (PVR) period in patients with repaired tetralogy of Fallot, which was followed by further time-related biological remodeling exemplified by further reduction in right ventricular (RV) end-systolic volume.1 Patients put forth for PVR following multidisciplinary review were opportunistically and serially approached by the research team (S.V.B.-N.) for study inclusion if they fulfilled the study inclusion criteria. The patients in …

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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00740870.

Since the original description of aortic valve replacement (AVR) with a pulmonary autograft by Donald Ross in 1967, 1 cardiac surgeons have had an uneasy relationship with this method for managing aortic valve disease. In many patients, the implanted autograft functions normally with no evidence of late deterioration, and thus is an ideal valve substitute. The Ross procedure has a special advantage in young children, because the implanted autograft can enlarge with somatic growth. 2 However, the operation is more complicated than standard prosthetic AVR because of the need for careful dissection during harvest of the pulmonary artery graft, the requirement for precise alignment of the graft within the aortic root, and the added potential for late dysfunction of the homograft or heterograft used to replace the native pulmonary valve.

Supplemental Digital Content is available in the text., 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

A 32-year-old woman with a history of tetralogy of Fallot (TOF) was referred for cardiac evaluation. She was diagnosed with TOF as an infant and at 8 months of age underwent complete repair, including ventricular septal defect closure, resection of right ventricular (RV) outflow tract (RVOT) muscle bundles, and pulmonary valvotomy. She was evaluated by a cardiologist at 17 years of age and was subsequently lost to follow-up because she thought she was “cured.” Overall, she feels well and denies cardiac symptoms. She runs 1 to 2 miles daily, although more slowly than her friends. She is considering having children. On physical examination, her vital signs were normal. She had a well-healed midline sternotomy scar. Her lungs were clear to auscultation. The heart rhythm was regular with a normal S1 and a single S2. There was a low-pitched, delayed diastolic murmur in the pulmonary area. Her ECG demonstrated normal sinus rhythm, a right bundle-branch block, and a QRS duration of 170 milliseconds. A transthoracic echocardiogram showed a dilated and hypokinetic RV, with severe pulmonary regurgitation (PR) and mild tricuspid regurgitation. There was no RVOT obstruction or residual ventricular septal defect. The left ventricle was normal in size and function, with mild mitral regurgitation. Because RV size and function were not well quantified with echocardiography, cardiac magnetic resonance imaging was performed. The RV end-diastolic and end-systolic volumes were 179 and 109 mL/m2, respectively, and the RV ejection fraction was 39%. A Holter study did not reveal significant ectopy or arrhythmia. A cardiopulmonary exercise test demonstrated a moderately depressed peak o2. Given her severe PR associated with a dilated and hypokinetic RV and moderately reduced exercise tolerance, she was referred for surgical pulmonary valve replacement (PVR). This woman is 1 of ≈1 million adults with congenital heart disease …

We read with great interest the recent article by Heng and colleagues1 describing the follow-up of 57 patients with repaired tetralogy of Fallot who underwent pulmonary valve replacement (PVR) with cardiac magnetic resonance imaging. They conclude that significant right heart structural reverse remodeling takes place immediately after PVR, followed by gradual further biological remodeling during follow-up. The analysis concerned 57 relatively healthy individuals, given their absence of contraindications to cardiac magnetic resonance, good kidney function, and the elective setting. The authors, however, did not disclose the selection criteria that left them with only 57 of a potentially larger …

I read with much interest the recent article and editorial by Cheatham et al1 and Petit2 in Circulation evaluating the long-term outcomes after transcatheter pulmonary valve implantation in 171 patients. In 148 patients who received the transcatheter pulmonary valve, 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). Their work is in keeping with the current research efforts that have reorientated from establishing …

Background— Treatment of right ventricular outflow tract obstruction is possible with a bare metal stent (BMS), although this treatment causes pulmonary regurgitation. In this study, we assessed the acute physiological effects of BMS versus percutaneous pulmonary valve implantation (PPVI) using an x-ray/magnetic resonance hybrid laboratory. Methods and Results— Fourteen consecutive children (median age, 12.9 years) with significant right ventricular outflow tract obstruction underwent BMS followed by PPVI. Magnetic resonance imaging (ventricular volumes and function and great vessel blood flow) and hemodynamic assessment (invasive pressure measurements) were performed before BMS, after BMS, and after PPVI; all were performed under general anesthesia in an x-ray/magnetic resonance hybrid laboratory. BMS significantly reduced the ratio of right ventricular to systemic pressure (0.75±0.17% versus 0.41±0.14%; P P =1.0). However, BMS resulted in free pulmonary regurgitation (21.3±10.7% versus 41.4±7.5%; P P 2 ; P =1.0) but was significantly increased after revalvulation with PPVI (41.0±8.0 mL/m 2 ; P =0.004). These improvements after PPVI were accompanied by a significant heart rate reduction (75.5±17.7 bpm after BMS versus 69.0±16.9 bpm after PPVI; P =0.006) at maintained cardiac output (2.5±0.5 versus 2.4±0.5 versus 2.7±0.5 mL · min −1 · m −2 ; P =0.14). Conclusion— Using an x-ray/magnetic resonance hybrid laboratory, we have demonstrated the superior acute hemodynamic effects of PPVI over BMS in patients with right ventricular outflow tract obstruction.

It has variably been estimated that between 800 000 and 1 million patients with congenital heart disease are now adults and that by 2010 more patients older than 16 years will undergo surgery for congenital heart disease than those younger than 16 years.1 This review will focus on the clinical aspects of identifying and caring for the portion of the unique population that have right ventricular (RV) outflow tract lesions. The left ventricle (LV) and RV both have inlet, apical, and outlet portions, although they differ considerably.2 The inlet of the RV includes the tricuspid valve, and it is separated from the pulmonary valve (PV) by the crista supraventricularis. This structure results in the PV being raised upward. The apical portion of the RV has coarse trabeculations. As shown in Figure 1, the septum is home to a large septomarginal (septal) trabeculation that divides into the anterior and posterior limbs in the outflow tract. A series of septoparietal trabeculations arise along the free wall. The crista supraventricularis inserts between these limbs and is made up of 3 components: the muscular outlet septum, the ventriculoinfundibular fold, and the inner curvature of the RV.3 The small part that separates the RV and LV cavities is the outlet or conal septum. A loop including the septal trabeculation, the moderator band, septoparietal trabeculations, and the outlet septum can be conceptualized as circling the RV outflow tract. The PV is supported by the circular muscular infundibulum rising outside the RV proper. Abnormalities involving the RV outflow tract involve malpositioning of 1 or more of these structures. Figure 1. The anatomy of the RV outflow tract.2 There is a large septomarginal (septal) trabeculation that divides into 2 limbs. The anterior limb supports the leaflets of the PV, and the posterior limb …

Background— We analyzed the incidence, risk factors and treatment options for stent fracture after percutaneous pulmonary valve (PPV) implantation (PPVI). Methods and Results— After PPVI, 123 patients had chest x-ray in anteroposterior and lateral projection, echocardiography, and clinical evaluation during structured follow-up. Of these 123 patients, 26 (21.1%) developed stent fracture 0 to 843 days after PPVI (stent fracture–free survival at 1 year, 85.1%; at 2 years, 74.5%; and at 3 years, 69.2%). Stent fracture was classified as type I: no loss of stent integrity (n=17); type II: loss of integrity with restenosis on echocardiography (n=8); and type III: separation of fragments or embolization (n=1). In a multivariate Cox regression, we analyzed various factors, of which 3 were associated with a higher risk of stent fracture: implantation into “native” right ventricular outflow tract ( P =0.04), no calcification along the right ventricular outflow tract (judged with fluoroscopy, P =0.02), recoil of PPV (qualitatively, PPV diameter in frontal or lateral plane with fully inflated balloon > diameter after balloon deflation, P =0.03). Substernal PPV location, high-pressure post-PPVI dilatation of PPV, pre-PPVI right ventricular outflow tract gradients, and other indicators of PPV compression or asymmetry did not pose increased risk. Patients with type I fracture remain under follow-up. Patients with type II fracture had 2nd PPVI or are awaiting such procedure, and 1 patient with type III fracture required surgical explantation. Conclusion— Stent fracture after PPVI can be managed effectively by risk stratification, systematic classification, and anticipatory management strategies. Serial x-ray and echocardiography are recommended for surveillance.

Background— The optimal treatment for dysfunctional right ventricle–to–pulmonary artery (RV-PA) conduits is unknown. Limited follow-up data on stenting of RV-PA conduits have been reported. Methods and Results— Between 1990 and 2004, deployment of balloon-expandable bare stents was attempted in 242 obstructed RV-PA conduits in 221 patients (median age, 6.7 years). Acute hemodynamic changes after stenting included significantly decreased RV systolic pressure (89±18 to 65±20 mm Hg, P P 5 years), with younger age, homograft conduit, conduit diameter ≤10 mm, diagnosis other than tetralogy of Fallot, Genesis stent, higher prestent RV:aortic pressure ratio, and stent malposition associated with shorter freedom from surgery. Tricuspid regurgitation and RV function did not change between stent implantation and subsequent surgery. Conclusions— Conduit stenting is an effective interim treatment for RV-PA conduit obstruction and prolongs conduit lifespan in most patients. Stent fractures were common but not associated with significant complications or earlier conduit reoperation.

Background— Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. Methods and Results— We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction P P −1 · min −1 , P =0.002) and anaerobic (14.4 to 16.2 mL · kg −1 · min −1 , P =0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P =0.05; mitral 4.7 to 5.5 cm/s, P =0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m 2 , P 2 , P =0.06) and ejection fraction (48.0% to 56.8%, P =0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m 2 , P =0.145), stroke volume (45.3 to 50.6 mL/m 2 , P =0.02), and ejection fraction (62.6% to 65.8%, P =0.03) increased. Conclusions— PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition.

Background— Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life. Methods and Results— Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4±17.2 to 50.4±14 mm Hg, P P P P −1 · m −2 , P −1 · m −2 , P =0.005) and effective RV stroke volume (37±7 versus 42±9 mL · beat −1 · m −2 , P =0.006) in 28 patients (age 19±8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V̇ o 2 max (26±7 versus 29±6 mL · kg −1 · min −1 , P Conclusions— PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.

Background— An estimated 275 000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems. Methods and Results— Mesenchymal stem cells were isolated from ovine bone marrow and characterized by their morphology and antigen expression through immunocytochemistry, flow cytometry, and capacity to differentiate into multiple cell lineages. A biodegradable scaffold was developed and characterized by its tensile strength and stiffness as a function of time in cell-conditioned medium. Autologous semilunar heart valves were then created in vitro using mesenchymal stem cells and the biodegradable scaffold and were implanted into the pulmonary position of sheep on cardiopulmonary bypass. The valves were evaluated by echocardiography at implantation and after 4 months in vivo. Valves were explanted at 4 and 8 months and examined by histology and immunohistochemistry. Valves displayed a maximum instantaneous gradient of 17.2±1.33 mm Hg, a mean gradient of 9.7±1.3 mm Hg, an effective orifice area of 1.35±0.17 cm 2 , and trivial or mild regurgitation at implantation. Gradients changed little over 4 months of follow-up. Histology showed disposition of extracellular matrix and distribution of cell phenotypes in the engineered valves reminiscent of that in native pulmonary valves. Conclusions— Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of >4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.

Until Blalock and Taussig developed the first palliative systemic-to-pulmonary shunt operation in 1945,1 tetralogy of Fallot (TOF) was a nearly uniformly lethal congenital cardiac anomaly. In the 5 decades since Lillehei and his colleagues at the University of Minnesota reported the first successful intracardiac repair in 1955,2 early mortality has decreased markedly from 50% to

Background— To gain insight into the pathogenesis of right ventricular (RV) cardiomyopathy and ventricular tachycardia (VT), we determined the clinical and electroanatomic characteristics and outcome of ablative therapy in consecutive patients with (1) RV dilatation, (2) multiple left bundle-branch block (LBBB)–type VTs, and (3) an abnormal endocardial substrate defined by contiguous electrogram abnormalities. Methods and Results— All 21 patients had detailed RV bipolar electrogram voltage mapping. Eighteen patients had simultaneous left ventricular (LV) mapping, including all 4 patients with right bundle-branch block (RBBB) VT. VT was ablated in 19 patients by use of focal and/or linear lesions with irrigated-tip catheters in 10 of 19 patients. Eighteen patients were men, age 47±18 years, and none had a family history of RV dysplasia. RV volume was 223±89 cm 3 . Electrogram abnormalities extended from perivalvular tricuspid valves (5 patients), pulmonic valves (6 patients), or both valves (10 patients). Electrogram abnormalities always involved free wall, spared the apex, and included the septum in 15 patients (71%). The area of abnormality was 55±37 cm 2 (range, 12 to 130 cm 2 ) and represented 34±19% of the RV. In 52 of 66 LBBB VTs, the origin was from the RV perivalvular region. LV perivalvular low-voltage areas noted in 5 patients were associated with a RBBB VT origin. No VT recurred after ablation in 17 patients (89%) during 27±22 months. Conclusions— In patients with RV cardiomyopathy and VT, (1) perivalvular electrogram abnormalities represent the commonly identified substrate and source of most VT, (2) LV perivalvular endocardial electrogram abnormalities and VT can occasionally be identified, and (3) aggressive ablative therapy provides long-term VT control.

Background— Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital lesion with high mortality. Therapy was exclusively surgical until recently, when the use of radiofrequency-assisted perforation of the atretic valve was introduced as a treatment option. This study analyzes the outcomes and morphological changes to right heart structures after percutaneous perforation and balloon dilation of the atretic valve. Methods and Results— Between April 1992 and August 2000, 30 patients with PA-IVS underwent attempted percutaneous valve perforation and balloon dilation of the pulmonary valve. Longitudinal echocardiographic measurements of the tricuspid valve diameter, right ventricular length and area were recorded. Z scores were calculated according to published formulas. Perforation was achieved in 27 patients. In 14 patients a modified Blalock-Taussig shunt was performed between 2 and 24 days after valve dilation. There were 3 early and 2 late deaths. Among the survivors (follow-up time of 1 to 87 months), 16 patients had a biventricular circulation, 3 a 1 ½-ventricle circulation, and 1 a Fontan operation. Four patients are awaiting further palliation. There was no significant change of the tricuspid valve Z score or right ventricular length Z score with time. Conclusions— Percutaneous balloon valvotomy is an effective treatment strategy for patients with PA-IVS provided that there is a patent infundibulum and a lack of a right ventricle–dependent coronary circulation. Despite the observation that right heart growth does not increase with body growth in early follow-up, it appears adequate to maintain a biventricular circulation in many patients.

A 14-year-old adolescent man from the Republic of Congo, with no personal medical history, presented with progressive shortness of breath and exercise limitation. On clinical examination, he had a 3/6 systolic murmur and regular cardiac rhythm, and cyanotic fingers and clubbing, as well. Pulmonary auscultation was normal. No recent episode of fever or shivering or peripheral sign of endocarditis were reported. Pulse oxymetry showed oxygen saturation at 64%. The diagnosis of Tetralogy of Fallot was subsequently established. Laboratory results showed a normal white blood cell count with no abnormalities. The initial echocardiogram showed a large perimembranous septal defect of 1.5-cm diameter, an aortic override, a predominant right-to-left ventricular shunt, a severe infundibular pulmonary stenosis, and right ventricular hypertrophy. Left ventricular diameter was 39 mm at end-diastole, and the left ventricular ejection fraction was normal. A 4-mm mobile element was unexpectedly visualized at the level of the pulmonary valve. An ECG-gated multidetector pulmonary computed tomography angiogram with iodinated contrast injection was then performed to explore this unusual finding. Preoperative transesophageal echocardiography was not …

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, occurring in 1 in 3,600 live births [1]. Complete repair of TOF was devised over 50 years ago (first reported by Lillehei in 1954) and can result in complete intra-cardiac repair in early infancy [2]. However, despite excellent short- and medium-term survival rates, the 30 year actuarial survival for patients repaired before their 5th birthday is 90 % of the expected survival rate and the annualized risk of death triples in the third postoperative decade [2, 3]. Late morbidity and mortality, in particular related to pulmonary incompetence, has been observed in many patients long after total repair.

Background —Chronic pulmonary regurgitation after repair of tetralogy of Fallot (TOF) may lead to right ventricular dilatation, which may be accompanied by ventricular tachycardia and sudden death. We aimed to examine the effects of pulmonary valve replacement (PVR) on (1) certain electrocardiographic markers predictive of monomorphic ventricular arrhythmia and sudden death and (2) sustained atrial flutter/fibrillation and monomorphic ventricular tachycardia. Methods and Results —We studied 70 patients who underwent PVR for pulmonary regurgitation and/or right ventricular outflow tract obstruction late after repair of TOF. Maximum QRS duration and QT dispersion were measured from standard ECGs before PVR and at the latest follow-up. Arrhythmia was defined as sustained atrial flutter/fibrillation or sustained monomorphic ventricular tachycardia. Concomitant intraoperative electrophysiological mapping and/or cryoablation were performed in 9 patients (60%) with preexisting ventricular tachycardia and 6 patients (50%) with preexisting atrial flutter. QRS duration remained unchanged in the study group ( P =0.46), but it was significantly prolonged ( P P P =0.32). Intraoperative ablation prevented recurrence of preexisting tachyarrhythmia (0 of 15 patients). Conclusions —PVR in patients with previous TOF repair and chronic pulmonary regurgitation leads to stabilization of QRS duration and, in conjunction with intraoperative cryoablation, to a decrease in the incidence of preexisting atrial and ventricular tachyarrhythmia. When applicable, this combined approach should be used in patients late after repair of TOF.

Background —Human tissue valves for aortic valve replacement have a limited durability that is influenced by interrelated determinants. Hierarchical linear modeling was used to analyze the relation between these determinants of durability and valve regurgitation measured by serial echocardiography. Methods and Results —In adult patients, 218 cryopreserved aortic allografts were implanted with the subcoronary (85) or the root replacement technique (133), and 81 patients had root replacement with a pulmonary autograft. Mean follow-up was 4.2 years (SD 2.7; range, 0 to 10.5). Patient age, operator experience with subcoronary implantation, and allograft diameter were independent predictors for reoperation. With repeated color Doppler echocardiography, the severity of aortic regurgitation was assessed by the jet length method and the jet diameter ratio. Multilevel hierarchical linear modeling was used to estimate initial aortic regurgitation (intercept), its change over time (slope), and the effect of 11 potential determinants of durability on aortic regurgitation. With the jet length method, the intercept was 0.94 grade and the slope was 0.11 grade per year. With the jet diameter ratio, the intercept was 0.34 and the annual increase was 0.01. Subcoronary implanted valves had more initial aortic regurgitation, but progression of aortic valve regurgitation did not differ from root replacement. At midterm follow-up, recipient age Conclusions —Subcoronary implantation has a learning curve, resulting in more initial aortic regurgitation and early reoperation compared with root replacement. In both techniques, progression of aortic regurgitation over time is small but accelerated in young adults.

Background —Pulmonary regurgitation can lead to severe right ventricular dysfunction, which is a delicate postoperative problem in the long-term follow-up of patients who had surgery for congenital heart diseases. Clinical conditions of patients suffering from pulmonary valve incompetence are improved by valve replacement with a prosthetic valve. To date, the surgical approach is the only option to replace a pulmonary valve. We report the first experience of percutaneous pulmonary valve implantation. Methods and Results —A fresh bovine jugular vein containing a native valve was sutured into a vascular stent and then cross-linked with a 0.6% glutaraldehyde solution for 36 hours. After being hand-crimped onto a balloon catheter, the device was inserted percutaneously according to standard stent-placing techniques. The valved stent was finally deployed in the position of the native pulmonary valve of the lamb. Hemodynamic evaluation was carried out before and 2 months after implantation. Anatomic evaluation was finally performed. Percutaneous pulmonary valve replacement was successful in 5 lambs. No complications were noted. Early and late angiographic and hemodynamic studies confirmed a good position of the stents with a competent valve at the end of the protocol. One stent was slightly stenotic, with macroscopically visible calcifications. Conclusions —Nonsurgical implantation of pulmonary valves is possible in the lamb. This new technique is similar to standard stent implantation. Thus, it should be feasible in humans, in whom it will lead to a significant reduction of reoperations in patients in need of pulmonary valve replacement.

The quest for a perfect heart valve substitute has been going on for half a century. In 1960, Lower et al1 described the feasibility of replacing the aortic valve of dogs with the native pulmonary valve. In 1967, Ross performed this procedure in humans.2 Ross transferred the pulmonary valve into the aortic root with the same technique used to implant aortic valve homograft3 (ie, the pulmonary sinuses of the pulmonary root were partially excised, and the pulmonary valve was secured in the recipient’s aortic root with 2 suture lines, 1 below and 1 above the aortic annulus, leaving the coronary artery orifices unobstructed). Although many surgeons gained experience with this type of aortic valve replacement using an aortic valve homograft, the Ross procedure did not gain widespread popularity until the late 1980s when the technique of aortic root replacement was described for this operation.4 In this approach, the aortic root is excised, the pulmonary root is sutured to the aortic annulus and ascending aorta, and the coronary arteries are reimplanted into the neoaortic root. This technique made the early outcomes more predictable than when the subcoronary technique was used, and enthusiasm for the Ross procedure increased during the 1990s. A voluntary international registry was developed, and thousands of patients were entered into that registry,5 but there have been no reports on long-term results. In the year 2000, we reported that the pulmonary autograft dilated and that the dilation was often accompanied by aortic insufficiency (AI) when the pulmonary autograft was used as a freestanding neoaortic root, whereas the techniques of subcoronary implantation and aortic root inclusion (pulmonary root inside of the aortic root) prevented dilation during a mean follow-up of 44 months.6 Other investigators confirmed our findings of dilation of the pulmonary autograft and …

Infective endocarditis (IE) is a potentially life-threatening disease that is treated with antimicrobial therapy alone or in combination with surgery. Surgical management of IE can optimize source control by removal of infected tissue, reduce morbidity from embolic events, and reduce mortality in the appropriate clinical context. Nevertheless, surgical management of IE is not indicated in all cases of IE. Consensus guidelines outline specific conditions for which surgery is recommended, but clinical application of these recommendations is unclear. In the present study, we found that an indication for surgery was present in the majority (74%) of IE patients; however, surgical therapy was performed for only 76% of patients with a surgical indication. Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, and embolization before surgical treatment, confirming that clinical practice is consistent with guideline-based recommendations for surgery. On the other hand, factors associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. Finally, operative risk assessment by the Society of Thoracic Surgeons IE score in this cohort provided prognostic information for survival 6 months beyond the operative period. Thus, in a large, multicenter, multinational cohort, we found that surgical decision making is largely consistent with the established guidelines and that the Society of Thoracic Surgeons IE score can provide prognostic information in IE beyond the operative period. See p 131. Because of a variety of cultural, social, and economic forces, blacks, whites, and, to a lesser extent, Hispanics have persistently been segregated spatially in most US metropolitan areas. The processes that lead to this spatial separation influence the distribution of health-promoting neighborhood resources and opportunities for socioeconomic mobility. As such, racial/ethnic residential segregation may represent an important contributor to racial/ethnic disparities …

Background —The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation. Methods and Results —Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were randomized to receive either 60% humidified oxygen or medical compressed air (room air) by a face mask. Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air. Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Q P ) were calculated. Foramen ovale volume blood flow (left ventricular cardiac output−Q P ) was estimated. Pulsatility index (PI) values of DA, RPA, LPA, and DPA were calculated. Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks, whereas between 31 and 36 weeks, the PI values of RPA, LPA, and DPA decreased ( P P P increased ( P P P Conclusions —Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation.

Diastolic dysfunction contributes significantly to the clinical syndrome of congestive heart failure in the settings of both preserved and impaired left ventricular (LV) systolic function.1,2 Over the past 20 years, the clinical diagnosis of diastolic dysfunction has been based largely on echocardiographic Doppler parameters of LV filling.3 The most important limitation of these parameters is their dependence on loading conditions. New practical and comprehensive methods of evaluating diastolic function are critically needed not only for diagnosis but also for testing emerging new therapies. Article p 2524 Recent work has elucidated both intracellular and extracellular mechanisms that contribute to diastolic dysfunction, and some progress has been made in finding new treatments for diastolic heart failure. Additional research has evaluated the contribution of LV architecture and its role in maintaining the normal contraction sequence that optimizes mechanical efficiency. The importance of systolic twist and the subsequent recoil that leads to diastolic untwisting was examined in the article by Notomi et al4 using tissue Doppler techniques in both normal subjects and patients with hypertrophic cardiomyopathy, at rest and during exercise. Leonardo DaVinci5 in the 16th century and Rushmore6 in the 1950s described the rotational motion of the left ventricle.7 In 1970, McDonald7 reported a study in which he placed radiopaque markers on the epicardium of patients undergoing closed mitral valvuloplasty. He demonstrated that the pre-ejection phase was characterized by descent of the base and a counterclockwise rotation of the epicardial surface of the left ventricle with a thrust of the apex toward the chest wall. In late systole, there was a slight clockwise rotation and apical retraction. Using blunt dissection, Torrent-Guasp et al8 demonstrated that the ventricles consist of a single myofiber band starting at the right ventricle just below the pulmonary valve and forming …