Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device.

To date, there has been limited investigation of bioabsorbable atrial septal defect (ASD) or patent foramen ovale (PFO) closure devices using clinically relevant large animal models. The purpose of this study is to explore the function and safety of a bioabsorbable ASD occluder (BAO) system for PFO and/or secundum ASD transcatheter closure. Using a sheep model, the intra-atrial septum was evaluated by intracardiac echo (ICE). If a PFO was not present, atrial communication was created via transseptal puncture. Device implantation across the intra-atrial communication was performed with fluoroscopic and ICE guidance. Our 1st generation device consisted of a main structure of thin Poly(L-lactide-co-epsilon-caprolactone) (PLCL) fibers, and an internal Poly glycolic acid (PGA) fabric. Four procedures validated procedure feasibility. Subsequently, device design was modified for improved transcatheter delivery. The 2nd generation device has a two-layered structure and was implanted in six sheep. Results showed procedural success in 9/10 (90%) animals. With deployment, the 1st generation device did not reform into its original disk shape and did not conform nicely along the atrial septum. The 2nd generation device was implanted in six animals, 3 out of 6 survived out to 1 year. At 1 year post implantation, ICE confirmed no residual shunting. By necropsy, biomaterials had partially degraded, and histology of explanted samples revealed significant device endothelialization and biomaterial replacement with a collagen layer. Our results demonstrate that our modified 2nd generation BAO can be deployed via minimally invasive percutaneous transcatheter techniques. The BAO partially degrades over 1 year and is replaced by host native tissues. Future studies are needed prior to clinical trials.

Comparison of the investigational device exemption and post-approval trials of the Melody transcatheter pulmonary valve.

OBJECTIVE: We compared 5-year outcomes of transcatheter pulmonary valve (TPV) replacement with the Melody TPV in the post-approval study (PAS) and the investigational device exemption (IDE) trial. BACKGROUND: As a condition of approval of the Melody TPV after the IDE trial, the Food and Drug Administration required that a PAS be conducted to evaluate outcomes of TPV replacement in a "real-world" environment. The 5-year outcomes of the PAS have not been published, and the IDE and PAS trials have not been compared. METHODS: The cohorts comprised all patients catheterized and implanted at 5 IDE sites and 10 PAS sites. Differences in trial protocols were detailed. Time-related outcomes and valve-related adverse events were compared between the two trials with Kaplan-Meier curves and log-rank testing. RESULTS: 167 patients (median age, 19 years) were catheterized and 150 underwent TPV replacement in the IDE trial; 121 were catheterized (median age, 17 years) and 100 implanted in the PAS. Freedom from hemodynamic dysfunction (p = .61) or any reintervention (p = .74) over time did not differ between trials. Freedom from stent fracture (p = .003) and transcatheter reintervention (p = .010) were longer in PAS, whereas freedom from explant (p = .020) and TPV endocarditis (p = .007) were shorter. Clinically important adverse events (AEs) were reported in 14% of PAS and 7.2% of IDE patients (p = .056); the incidence of any particular event was low in both. CONCLUSIONS: Hemodynamic and time-related outcomes in the PAS and IDE trials were generally similar, confirming the effectiveness of the Melody TPV with real-world providers. There were few significant complications and limited power to identify important differences in AEs. The lack of major differences in outcomes between the two studies questions the usefulness of mandated costly post-approval studies as part of the regulatory process for Class III medical devices.

Association between patient age at implant and outcomes after transcatheter pulmonary valve replacement in the multicenter Melody valve trials.

OBJECTIVES: To investigate whether age and valve size at implant contribute to outcomes after Melody transcatheter pulmonary valve replacement (TPVR). BACKGROUND: Patient age and valve size at implant contribute to longevity of surgical pulmonary valves. METHODS: All patients discharged with a Melody valve in the pulmonary position, as part of three prospective Melody valve multicenter studies, comprised the study cohort. Acute and time-related outcomes were analyzed according to age: children (≤12 years), adolescents (13-18 years), young adults (19-29 years), and older adults (≥30 years). RESULTS: Successful Melody valve implantation occurred in 49 children, 107 adolescents, 96 young adults, and 57 older adults. Pediatric patients (≤18 years) were more likely to have TPVR for conduit stenosis than adults (62% vs. 44%); children had the smallest conduits. After TPVR, pediatric and adult patients had similar decreases in right ventricular (RV) size by MRI, but adults had improved percentage predicted peak VO2 (58% preimplant to 64% postimplant, p = .02) and FEV1 (69% pre to 71% post, p = .005). Younger age was associated with shorter freedom from RVOT dysfunction, reintervention, and explant. Children had the shortest freedom from endocarditis (p = .041), but all other groups had 5-year freedom from endocarditis of ≥90%. CONCLUSIONS: Younger age was associated with shorter time to RVOT dysfunction, reintervention, and explant after Melody TPVR. Patients ≥13 years of age were at low risk for endocarditis and explant to 5 years. A better understanding of time-related outcomes by age will aid in the comparison of therapeutic options for TPVR candidates. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00740870 (NCT00740870), https://clinicaltrials.gov/ct2/show/NCT01186692 (NCT01186692), and https://clinicaltrials.gov/ct2/show/NCT00688571 (NCT00688571).

Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves: An International, Multicenter Registry Study.

BACKGROUND: Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. METHODS AND RESULTS: An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. CONCLUSIONS: TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.

Echocardiographic right ventricular function correlations with cardiac catheterisation data in biventricular congenital heart patients.

BACKGROUND: Newer echocardiographic techniques may allow for more accurate assessment of right ventricular function. Adult studies have correlated these echocardiographic measurements with invasive data, but minimal data exist in the paediatric congenital heart population. The purpose of this study was to evaluate echocardiographic measurements that correlate best with right ventricular systolic and diastolic catheterisation parameters. METHODS: Patients with two-ventricle physiology who underwent simultaneous echocardiogram and cardiac catheterisation were included in this study. Right ventricular systolic echocardiographic data included fractional area change, displacement, tissue Doppler imaging s' wave, global longitudinal strain, and strain rate s' wave. Diastolic echocardiographic data included tricuspid E and A waves, tissue Doppler imaging e' and a' waves, and strain rate e' and a' waves. E/tissue Doppler imaging e', tissue Doppler imaging e'/tissue Doppler imaging a', E/strain rate e', and strain rate e'/strain rate a' ratios were also calculated. Catheterisation dP/dt was used as a marker for systolic function and right ventricular end-diastolic pressure for diastolic function. RESULTS: A total of 32 patients were included in this study. The median age at catheterisation was 3.1 years (0.3-17.6 years). The DP/dt was 493±327 mmHg/second, and the right ventricular end-diastolic pressure was 7.7±2.4 mmHg. There were no significant correlations between catheterisation dP/dt and systolic echocardiographic parameters. Right ventricular end-diastolic pressure correlated significantly with strain rate e' (r=-0.4, p=0.02), strain rate a' (r=-0.5, p=0.03), and E/tissue Doppler imaging e' (r=0.4, p=0.04). CONCLUSION: Catheterisation dP/dt did not correlate with echocardiographic measurements of right ventricular systolic function. Strain rate and tissue Doppler imaging analysis significantly correlated with right ventricular end-diastolic pressure. These values should be further studied to determine whether they may be used as an alternative method to estimate right ventricular end-diastolic pressure in this patient population.

Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary valve replacement in the US melody valve investigational device exemption trial.

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.

Accuracy of Imaging Modalities in Detection of Baffle Leaks in Patients Following Atrial Switch Operation.

AIMS: Patients with dextro-transposition of the great arteries (d-TGA) status post atrial switch operation are vulnerable to complications such as baffle leaks. The best noninvasive imaging modality to detect baffle leaks is unknown. The purpose of this study was to determine the sensitivity and specificity of different noninvasive imaging modalities in the detection of baffle leaks in this population. METHODS AND RESULTS: A single center retrospective chart review of atrial switch patients was performed. Sensitivity, specificity, negative predictive value, and positive predictive value for detecting leaks were calculated for transthoracic echocardiogram (TTE) with and without agitated saline, transesophageal echocardiogram (TEE) with and without agitated saline, and cardiac magnetic resonance imaging (cMRI). Studies were included if performed within 1 year of catheterization. Angiography via catheterization was used as the gold standard for the detection of baffle leaks. Fifty-eight atrial switch patients (54 Mustards: four Sennings) from a single pediatric center, undergoing 76 catheterizations, were analyzed. Thirty-nine catheterizations documented a baffle leak. Overall combination of sensitivity and specificity was better in agitated saline studies (TTE: sensitivity 71.4%, specificity 100%; TEE: sensitivity 100%, specificity 92.3%) versus nonagitated studies (TTE: sensitivity 50.0%, specificity 100%; TEE: sensitivity 83.3%, specificity 77.8%; or cMRI: sensitivity 66.7%, specificity 100%). CONCLUSION: TTE or TEE with agitated saline is superior to cardiac magnetic resonance imaging or nonagitated saline TTE and TEE in detecting baffle leaks in atrial switch patients. Agitated saline studies should be performed in this population when looking for baffle leaks.

Results of a Feeding Protocol in Patients Undergoing the Hybrid Procedure.

Neonates with single-ventricle physiology are at increased risk of developing gastrointestinal morbidities. Feeding protocols in this patient population have been shown to decrease feeding complications after the Norwood procedure, but no data exist to determine the effectiveness of a feeding protocol in patients undergoing the hybrid procedure. Goal of this study was to examine the impact of a standardized feeding protocol on the incidence of overall postoperative gastrointestinal morbidity after the hybrid procedure. Retrospective chart review was performed on neonates undergoing the hybrid procedure. Neonates were divided into two groups, pre-feeding protocol (pre-FP), which encompassed the years 2002-2008, and post-feeding protocol (post-FP), which encompassed the years 2011-2014. Preoperative, operative, and postoperative data were collected. T test or Fisher's exact test was used for analysis. p < 0.05 was considered significant. Seventy-three neonates were in the pre-FP and 52 neonates were in the post-FP. There were no significant differences between the pre-FP and the post-FP in cardiac diagnosis (62 HLHS, 11 other vs. 39 HLHS, 13 other, respectively). Pre-FP underwent hybrid procedure later than the post-FP (9.1 ± 5.8 vs. 5.7 ± 3.4 days, respectively, p < 0.01) and achieved full enteral feeds earlier than the post-FP (3.2 + 2.9 vs. 7.8 + 3.9 days, respectively, p < 0.01). The incidence of necrotizing enterocolitis was higher in the pre-FP versus post-FP [11.0 % (8/65) vs. 5.8 % (3/49), respectively, p = 0.36]. Though not significant, the incidence of necrotizing enterocolitis decreased by almost 50 % after initiating a feeding protocol in patients undergoing the hybrid procedure. This is consistent with previous studies showing beneficial results of a feeding protocol in this complex patient population.

Arrhythmias After Stage I Hybrid Palliation in Single-Ventricle Patients.

The hybrid procedure is an alternative palliative strategy for patients with single-ventricle physiology. No data exist documenting the incidence of arrhythmias after the hybrid procedure. Goal of this study was to determine the incidence and type of arrhythmias in patients undergoing the hybrid procedure. A retrospective chart review was performed including all patients undergoing the hybrid procedure between January of 2010 through December of 2013. Sixty-five patients underwent the hybrid procedure during this time period (43 HLHS, 22 other). Average gestational age at admission was 37.7 weeks. Average age at time of procedure was 7.6 days. Five patients had documented arrhythmias (7.7 %). Four were supraventricular tachycardias, and 1 was a sinus bradycardia. One patient with arrhythmia died during hospitalization, and another patient with arrhythmia died during the interstage period. Hybrid palliation for patients with single-ventricle physiology has a low incidence of arrhythmias. In this cohort of patients, arrhythmias did not contribute to mortality. There was a trend toward association between arrhythmias and longer total length of hospital stay.

Arrhythmias Following Comprehensive Stage II Surgical Palliation in Single Ventricle Patients.

Post-operative arrhythmias are common in pediatric patients following cardiac surgery. Following hybrid palliation in single ventricle patients, a comprehensive stage II palliation is performed. The incidence of arrhythmias in patients following comprehensive stage II palliation is unknown. The purpose of this study is to determine the incidence of arrhythmias following comprehensive stage II palliation. A single-center retrospective chart review was performed on all single ventricle patients undergoing a comprehensive stage II palliation from January 2010 to May 2014. Pre-operative, operative, and post-operative data were collected. A clinically significant arrhythmia was defined as an arrhythmia which led to cardiopulmonary resuscitation or required treatment with either pacing or antiarrhythmic medication. Statistical analysis was performed with Wilcoxon rank-sum test and Fisher's exact test with p < 0.05 significant. Forty-eight single ventricle patients were reviewed (32 hypoplastic left heart syndrome, 16 other single ventricle variants). Age at surgery was 185 ± 56 days. Cardiopulmonary bypass time was 259 ± 45 min. Average vasoactive-inotropic score was 5.97 ± 7.58. Six patients (12.5 %) had clinically significant arrhythmias: four sinus bradycardia, one 2:1 atrioventricular block, and one slow junctional rhythm. No tachyarrhythmias were documented for this patient population. Presence of arrhythmia was associated with elevated lactate (p = 0.04) and cardiac arrest (p = 0.002). Following comprehensive stage II palliation, single ventricle patients are at low risk for development of tachyarrhythmias. The most frequent arrhythmia seen in these patients was sinus bradycardia associated with respiratory compromise.

Ultrasound assessment of mesenteric blood flow in neonates with hypoplastic left heart before and after hybrid palliation.

BACKGROUND: Altered mesenteric perfusion may be a contributor to the development of necrotising enterocolitis in patients with hypoplastic left heart syndrome. The goal of this study was to document mesenteric flow patterns in patients with hypoplastic left heart syndrome pre- and post-hybrid procedure. METHODS: A prospective study on all patients with hypoplatic left heart syndrome undergoing the hybrid procedure was conducted. Doppler ultrasound analysis of the coeliac and superior mesenteric artery was performed. RESULTS: A total of 13 patients were evaluated. There was a significant difference in the coeliac artery effective velocity-time intergral pre- and post-hybrid procedure (8.69±3.84 versus 12.51±4.95 cm, respectively). There were significant differences in the superior mesenteric artery antegrade velocity-time integral pre- and post-hybrid procedure (6.86±2.45 versus 10.52±2.64 cm, respectively) and superior mesenteric artery effective velocity-time integral pre- and post-hybrid procedure (6.22±2.68 versus 9.73±2.73 cm, respectively). There were no significant differences between the coeliac and superior mesenteric artery Doppler indices in the pre-hybrid procedure; there were, however, significant differences in the post-hybrid procedure between coeliac and superior mesenteric artery antegrade velocity-time integral (13.8 2±5.60 versus 10.52±2.64 cm, respectively) and effective velocity-time integral (13.04±4.71 versus 9.73±2.73 cm, respectively). CONCLUSION: Doppler mesenteric indices of perfusion improve in patients with hypoplastic left heart syndrome after the hybrid procedure; however, there appears to be preferential flow to the coeliac artery versus the superior mesenteric artery in these patients post-procedure.

Mustard baffle obstruction and leak - How successful are percutaneous interventions in adults?

Atrial switch operations for D-Transposition of the great arteries (D-TGA) were performed until the late 20th century. These patients have substantial rates of re-operation, particularly for baffle related complications. This study sought to analyze the efficacy of percutaneous transcatheter intervention (PTI) for baffle leak and/or stenosis in adult atrial switch patients. Adult patients with a prior atrial switch operation who underwent heart catheterization (2002-2014) at a tertiary adult congenital heart disease referral center were retrospectively analyzed. In 58 adults (30 ± 8 years, 75% men, 14% New York Heart Association (NYHA) functional class ≥2) who underwent 79 catheterizations, PTI was attempted in 50 (baffle leak (n = 10, 20%), stenosis (n = 27, 54%), or both (n = 13, 26%)). PTI was successful in 45 and 5 were referred for surgery due to complex anatomy. A total of 40 bare metal stents, 18 covered stents, 16 occlusion devices, 2 angioplasties, and 1 endovascular graft were deployed. In isolated stenosis, there was improvement in NYHA functional class after PTI (8 vs. 0 patients were NYHA FC > 2, p = 0.004), which was matched by improvement in maximal oxygen consumption on exercise testing (VO2) (25.1 ± 5.4 mL/kg/min vs. 27.9 ± 9 mL/kg/min, p = 0.03). There were no procedure-related deaths or emergent surgeries in this cohort. This single-center cohort is the largest reported series of adult atrial switch operation patients who have undergone PTI for baffle stenosis and/or leak. We demonstrate that PTI with an expert multi-disciplinary team is a safe and effective alternative to surgery in adult patients with an atrial switch operation.

Comparing echocardiographic assessment of systolic function with catheterization data in patients with single right ventricles.

PURPOSE: Echocardiographic evaluation of systolic function in patients with single right ventricles (SRV) is important but remains challenging. Minimal data exist correlating echocardiographic indices with catheterization data in this population. The goal of this study was to evaluate which echocardiographic measurement correlated best with dP/dt (max) obtained by cardiac catheterization in SRV patients. METHODS: Patients with SRV physiology who underwent simultaneous echocardiography and cardiac catheterization were evaluated. Echocardiographic data included fractional area change % (FAC), displacement, TDI s'wave, myocardial performance index (MPI), global systolic strain, and global SR s wave. Maximum positive rate of ventricular pressure change measured as dP/dt (max) was obtained from the cardiac catheterization report. Correlations of echocardiographic and catheterization variables were examined using the Pearson correlation. RESULTS: Twenty-seven SRV patients were studied. Median age at the time of the catheterization was 11.4 months (range 0 - 132 months). dP/dt (max) values ranged from 337-1860 mmHg/s with a median of 994 mmHg/s. Mean FAC was 27.15 +/- 7.13%, displacement was 7.35 +/- 2.88 mm, TDI s' was 4.98 +/- 1.93 cm/sec, MPI was 0.41 +/- 0.17, global strain was-14.85 +/- 4.32%, and global SR s wave was -1.03 +/- 0.34 sec(-1). There were no significant correlations between dP/dt (max) and any of the echocardiographic measurements of systolic function in SRV patients. CONCLUSION: In patients with SRV physiology, catheterization-derived dP/dt (max) did not correlate with echocardiographic measurements of systolic function. Larger studies are needed to determine which non-invasive parameter best describes systolic function in patients with SRV.

Percutaneous Balloon-Expandable Stent Implantation to Treat Transverse Aortic Arch Obstruction: Medium- to Long-Term Outcomes of a Retrospective Multicenter Study.

BACKGROUND: Transverse aortic arch obstruction is a challenging lesion for which stent implantation provides a potentially important alternate therapy. The objectives were to evaluate the technical, procedural, and medium-to-long-term clinical outcomes of percutaneous stent implantation of transverse aortic arch obstruction. METHODS: This is a retrospective, multicenter study of transverse aortic arch stent implantation. Univariable and multivariable analyses were performed. RESULTS: Index catheterization included 187 stent implants in 146 patients. The median age is 14.3 years (interquartile range, 9.3-19), weight is 53 kg (30-69), and follow-up is 53 months (12-120). The most common stent design was open cell (n=90, 48%). Stents overlapped 142 arch vessels (37 carotid arteries) in 118 (81%) cases. Technical and procedural success rates were 100% and 88%, respectively. Lower weight (P=0.018), body surface area (P=0.013), and minimum-to-descending aortic diameter ratio (P<0.001) were associated with higher baseline aortic gradient. The residual gradient was inversely associated with implant and final dilation diameters (P<0.001). The combined incidence of aortic injury and stent-related complications was 14%. There were no reports of abnormal brain scans or stroke. Blood pressure cuff gradient, echocardiographic arch velocity, and hypertension rates improved within 1-year follow-up with increased antihypertensive medication use. Reintervention was reported in 60 (41%) patients at a median of 84 (22-148) months to first reintervention. On multivariable logistic regression, residual aortic gradient >10 mm Hg was associated with increased odds of reintervention at all time points when controlling for each final dilation diameter, weight, and minimum-to-descending aortic diameter ratio. CONCLUSIONS: Transverse aortic arch stent implantation has high rates of technical, procedural, and medium-to-long-term clinical success. Aortic gradient >10 mm Hg is associated with increased odds of reintervention at 1-year and most recent follow-ups. Open cell stent design was frequently used for its advantages in conformability, perfusion of arch vessels, low fracture rate, and the ability to perform effective angioplasty of side cells.

The Medtronic Melody® transcatheter pulmonary valve implanted at 24-mm diameter--it works.

OBJECTIVES: We report the Melody valve implanted and/or expanded to 24-mm diameter. BACKGROUND: The Medtronic Melody valve has been implanted up to 22 mm in the pulmonary position for over a decade. METHODS: A retrospective chart review was performed on 82 patients who underwent Melody valve implant. Technical implant method, pre- and postimplant echocardiographic findings, and initial follow-up were reviewed. RESULTS: Between 04/2008 and 12/2011, 13 Melody valves were successfully implanted in 11 patients, median age 35 years (range 16-61 years), in the pulmonary (bioprosthetic valve, right ventricle to pulmonary artery conduit, native valve) position (n = 9), tricuspid position (bioprosthetic valve n = 3), and aortic position (bioprosthetic valve n = 1). Ten valves were delivered on a 24-mm balloon in balloon catheter and three were implanted using a 22-mm Ensemble balloon delivery system, followed by postdilation using a 24-mm × 2-cm Atlas balloon catheter. Postimplant, the median peak systolic gradient across the pulmonary valve was 7 mm Hg and median gradient across the tricuspid valve was 3 mm Hg. There was no change in gradient across the Melody valve in the aortic position where valve prosthesis-patient mismatch was present. Postimplant intracardiac echocardiography demonstrated none or mild valve regurgitation. No more than mild regurgitation was noted at a median follow-up of 9.5 months. CONCLUSIONS: The Melody valve can be implanted at 24 mm in the stenotic/regurgitant bioprosthetic pulmonary, tricuspid, and aortic valve, dysfunctional right ventricle to pulmonary artery conduit, and the native right ventricular outflow tract, whereas the valve remains competent with only mild regurgitation.

QRS duration changes in patients with hypoplastic left heart syndrome undergoing hybrid palliation: prehybrid to post-Fontan.

BACKGROUND: QRS prolongation has been shown to be a predictor of mortality in patients with certain forms of congenital heart disease. QRS changes have not been well described in patients with single ventricle physiology, particularly in those undergoing the hybrid procedure. OBJECTIVE: To describe QRS changes in a cohort of patients with hypoplastic left heart syndrome (HLHS) who underwent hybrid palliation and to evaluate if QRS duration is associated with mortality. METHODS: Chart review of 54 patients with HLHS who underwent hybrid procedure between 2002 and 2009 was performed. Patients awaiting surgical palliation were excluded. Patients who survived Fontan completion (HLHS-S, n = 30) were compared to non-survivor (HLHS-NS, n = 24). Electrocardiograms were reviewed for maximal QRS duration (ms) at three pre- and postsurgical stages: (1) hybrid procedure, (2) comprehensive stage 2 procedure, and (3) Fontan procedure. RESULTS: In HLHS-S, there was a significant increase in QRS from birth to Fontan completion (15.6 ± 9.3 ms). QRS duration increased 8.5 ± 8.9 ms between posthybrid to precomprehensive stage 2, and 5.4 ± 9.7 ms between postcomprehensive stage 2 to Fontan. Following Fontan procedure, mean QRS decreased 4.3 ± 8.5 ms. There was no significant mean difference in QRS change between HLHS-S and HLHS-NS following hybrid procedure. Pre- and posthybrid and pre- and postcomprehensive stage 2 QRS durations were not different between HLHS-S and HLHS-NS who underwent a comprehensive stage 2 procedure. There was a significant difference in QRS difference following comprehensive stage 2 in HLHS-S (0.9 ± 7.1 ms) compared to HLHS-NS (-7.1 ± 10.0 ms). CONCLUSIONS: QRS duration significantly increased from hybrid to Fontan completion in HLHS-S. There was a significant decrease in QRS duration in patients who died following comprehensive stage 2 procedure. Larger studies are needed to assess the significance of these QRS changes.

Predictors of ductus arteriosus in-stent stenosis in the hybrid approach to hypoplastic left heart syndrome.

The hybrid approach to palliation of hypoplastic left heart syndrome using pulmonary artery bands, a patent ductus arteriosus (PDA) stent, and atrial septostomy has been well described. One potential complication of hybrid stage 1 palliation is the development of neointimal formation and in-stent stenosis (ISS). This study aimed to identify predictors of ISS development. Patients who underwent hybrid stage 1 palliation between 2002 and 2010 were included in the study. The clinical information included oxygen saturation, weight, vital signs, and medications. Echocardiographic data included ventricular function, degree of tricuspid regurgitation, and velocity through the PDA stent and pulmonary artery bands. Hemodynamic data from interstage catheterizations were similarly noted. Patients who developed clinically significant ISS requiring either transcatheter intervention or early stage 2 repair were compared with those who did not. Of the 66 patients included in the study, 40 were boys (61 %). The median age at hybrid palliation was 7 days (range, 1-93 days), and the median initial weight was 3.2 kg (range, 1.4-5 kg). In 13 patients (20 %), ISS developed. The mean initial weight was significantly greater in the ISS group (3.5 ± 0.5 vs. 3.0 ± 0.6 kg) (p = 0.03). The mean oxygen saturations did not differ significantly between the no-ISS group (82.2 % ± 5.7 %) and the ISS group (81.4 % ± 2.0 %) (p = 0.31). The mean PDA velocities were higher in the ISS group (2.7 ± 0.4 m/s) and increased at a faster rate than in the no-ISS group at (2.4 ± 0.4 m/s) (p = 0.01). The degree of tricuspid regurgitation, ventricular function, and pulmonary artery band gradients shown by echocardiography were similar in the two groups. The development of ISS after hybrid stage 1 palliation can lead to interstage interventions or earlier comprehensive stage 2 repair. Patients with greater initial weight and a lower stent-to-weight ratio are more likely to develop ISS. The cause of ISS is complex, and additional investigation of its etiology currently is ongoing.

1-Year Outcomes in a Pooled Cohort of Harmony Transcatheter Pulmonary Valve Clinical Trial Participants.

BACKGROUND: The Harmony transcatheter pulmonary valve (TPV) is the first U.S. Food and Drug Administration-approved device for severe pulmonary regurgitation (PR) in the native or surgically repaired right ventricular outflow tract (RVOT). OBJECTIVES: One-year safety and effectiveness of the Harmony TPV were evaluated in patients from the Harmony Native Outflow Tract Early Feasibility Study, Harmony TPV Pivotal Study, and Continued Access Study, representing the largest cohort to date of Harmony TPV recipients. METHODS: Eligible patients had severe PR by echocardiography or PR fraction ≥ 30% by cardiac magnetic resonance imaging and clinical indications for pulmonary valve replacement. The primary analysis included 87 patients who received a commercially available TPV22 (n = 42) or TPV25 (n = 45) device; 19 patients who received an early device iteration prior to its discontinuation were evaluated separately. RESULTS: In the primary analysis, median patient age at treatment was 26 years (IQR: 18-37 years) in the TPV22 group and 29 years (IQR: 19-42 years) in the TPV25 group. At 1 year, there were no deaths; 98% of TPV22 and 91% of TPV25 patients were free from the composite of PR, stenosis, and reintervention (moderate or worse PR, mean RVOT gradient >40 mmHg, device-related RVOT reoperation, and catheter reintervention). Nonsustained ventricular tachycardia occurred in 16% of patients. Most patients had none/trace or mild PR (98% of TPV22 patients, 97% of TPV25 patients). Outcomes with the discontinued device are reported separately. CONCLUSIONS: The Harmony TPV device demonstrated favorable clinical and hemodynamic outcomes across studies and valve types through 1 year. Further follow-up will continue to assess long-term valve performance and durability.

Long-Term Outcomes After Melody Transcatheter Pulmonary Valve Replacement in the US Investigational Device Exemption Trial.

BACKGROUND: The Melody valve was developed to extend the useful life of previously implanted right ventricular outflow tract (RVOT) conduits or bioprosthetic pulmonary valves, while preserving RV function and reducing the lifetime burden of surgery for patients with complex congenital heart disease. METHODS: Enrollment for the US Investigational Device Exemption study of the Melody valve began in 2007. Extended follow-up was completed in 2020. The primary outcome was freedom from transcatheter pulmonary valve (TPV) dysfunction (freedom from reoperation, reintervention, moderate or severe pulmonary regurgitation, and/or mean RVOT gradient >40 mm Hg). Secondary end points included stent fracture, catheter reintervention, surgical conduit replacement, and death. RESULTS: One hundred seventy-one subjects with RVOT conduit or bioprosthetic pulmonary valve dysfunction were enrolled. One hundred fifty underwent Melody TPV replacement. Median age was 19 years (Q1-Q3: 15-26). Median discharge mean RVOT Doppler gradient was 17 mm Hg (Q1-Q3: 12-22). The 149 patients implanted >24 hours were followed for a median of 8.4 years (Q1-Q3: 5.4-10.1). At 10 years, estimated freedom from mortality was 90%, from reoperation 79%, and from any reintervention 60%. Ten-year freedom from TPV dysfunction was 53% and was significantly shorter in children than in adults. Estimated freedom from TPV-related endocarditis was 81% at 10 years (95% CI, 69%-89%), with an annualized rate of 2.0% per patient-year. CONCLUSIONS: Ten-year outcomes from the Melody Investigational Device Exemption trial affirm the benefits of Melody TPV replacement in the lifetime management of patients with RVOT conduits and bioprosthetic pulmonary valves by providing sustained symptomatic and hemodynamic improvement in the majority of patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00740870.

A first-in-human phase I/IIa gene transfer clinical trial for Duchenne muscular dystrophy using rAAVrh74.MCK.GALGT2.

In a phase 1/2, open-label dose escalation trial, we delivered rAAVrh74.MCK.GALGT2 (also B4GALNT2) bilaterally to the legs of two boys with Duchenne muscular dystrophy using intravascular limb infusion. Subject 1 (age 8.9 years at dosing) received 2.5 × 1013 vector genome (vg)/kg per leg (5 × 1013 vg/kg total) and subject 2 (age 6.9 years at dosing) received 5 × 1013 vg/kg per leg (1 × 1014 vg/kg total). No serious adverse events were observed. Muscle biopsy evaluated 3 or 4 months post treatment versus baseline showed evidence of GALGT2 gene expression and GALGT2-induced muscle cell glycosylation. Functionally, subject 1 showed a decline in 6-min walk test (6MWT) distance; an increase in time to run 100 m, and a decline in North Star Ambulatory Assessment (NSAA) score until ambulation was lost at 24 months. Subject 2, treated at a younger age and at a higher dose, demonstrated an improvement over 24 months in NSAA score (from 20 to 23 points), an increase in 6MWT distance (from 405 to 478 m), and only a minimal increase in 100 m time (45.6-48.4 s). These data suggest preliminary safety at a dose of 1 × 1014 vg/kg and functional stabilization in one patient.