Trileaflet Semilunar Valve Reconstruction: Acute Porcine in Vivo Evaluation.

Objective: The surgical treatment of malformed semilunar valves in congenital heart defects is challenging in terms of providing both longevity and the potential to grow with the recipient. We investigated a new surgical technique "Trileaflet Semilunar Valve Reconstruction" in an acute porcine model, a technique with geometrical properties that could remain sufficient and allow for some growth with the child. Methods: An acute 60-kg porcine model was used. With echocardiography, baseline pulmonary valvular geometry and hemodynamics were investigated. On cardiopulmonary bypass, the pulmonary leaflets were explanted, and the Trileaflet Semilunar Valve Reconstruction was performed with customized homograft-treated pericardial neo-leaflets. Off bypass, hemodynamics was reassessed. Results: Twelve animals were investigated. The neo-valves were found sufficient in ten animals and with minimal regurgitation in two animals. The neo-valve had a peak gradient of 3 ± 2 mm Hg with a peak velocity of 0.8 ± 0.2 m/s. The coaptation in the neo-valve had a mean increase of 4 ± 3 mm, P < .001. The neo-valve had a windmill shape in the echocardiographic short-axis view, and the neo-leaflets billowed at the annular plane in the long-axis view. Conclusions: In this acute porcine model, the neo-valve had no clinically significant regurgitation or stenosis. The neo-valve had an increased coaptation, a windmill shape, and leaflets that billowed at the annular plane. These geometric findings may allow for sustained sufficiency as the annular and pulmonary artery dimension increase with the child's growth. Further long-term studies should be performed to evaluate the efficacy and the growth potential.

A handsewn pericardial valved pulmonary conduit: pulsatile flow loop in vitro and acute porcine in vivo evaluation.

OBJECTIVES: Right ventricle to pulmonary artery anatomic discontinuity is common in complex congenital heart malformations. Handsewn conduits are a practised method of repair. In a proof-of-concept study, we evaluated pulmonary valve replacement with a handsewn pericardial valved pulmonary conduit in vitro and in vivo. METHODS: A pulsatile flow-loop model (in vitro) and an acute 60-kg porcine model (in vivo) were used. With echocardiography and pressure catheters, baseline geometry and fluid dynamics were measured. The pulmonary valve was replaced with a handsewn glutaraldehyde-treated pericardial valved pulmonary conduit corresponding to a 21-mm prosthetic valve, after which geometric measurements and fluid dynamics were reassessed. RESULTS: In vitro, 15 pulmonary trunks at 4 l/min and 13 trunks at 7 l/min, and in vivo, 11 animals were investigated. The valved pulmonary conduit was straightforward to produce at the operating table and easy to suture in place. All valves were clinically sufficient in vitro and in vivo. The mean transvalvular pressure gradient in the native valve and the conduit was 8 mmHg [standard deviation (SD): 2] and 7 mmHg (SD: 2) at 4 l/min in vitro, 19 mmHg (SD: 3) and 17 mmHg (SD: 4) at 7 l/min in vitro and 3 mmHg (SD: 2) and 6 mmHg (SD: 3) in vivo. CONCLUSIONS: Our proof-of-concept demonstrates no early evidence of structural damage to the conduit, and the fluid dynamic data were acceptable. The handsewn conduit can be produced at the operating table.

Impaired left and right systolic ventricular capacity in corrected atrial septal defect patients.

Resting right ventricular (RV) systolic function has in some studies been shown to be impaired after correction of an atrial septal defect (ASD) whereas impairment of left ventricular (LV) systolic function is uncertain. In the present study we examine the LV and RV systolic response to exercise in patients with a previously corrected ASD in order to investigate the myocardial capacity. Thirty-six adult ASD patients with a corrected isolated secundum ASD and eighteen adult age-matched controls underent a semi-supine exercise stress echocardiographic examination. At rest, LV parameters were comparable between groups, and RV global longitudinal strain (RV-GLS) was lower for the ASD group (-18.5%, 95% CI -20.0--17.0%) compared with controls (-24.5%, 95% CI -27.7--22.4%, p < 0.001). At peak exercise, LV ejection fraction (LVEF) was lower for ASD patients (61%, 95% CI 58-65%) compared with controls (68%, 95% CI 64-73% p = 0.01). Peak LV global longitudinal strain (LV-GLS) was borderline significantly lower (ASD: -18.4%, 95% CI -20.2--16.6%, controls: -21.3%, 95% CI -23.6--19.0%, p = 0.059). Both RVEF (ASD: 64%, 95% CI 60-68%, controls: 73%, 95% CI 65-80%, p = 0.05) and tricuspid annular plane systolic excursion (TAPSE) (ASD: 2.5 cm, 95% CI 2.3-2.7 cm, controls: 3.2 cm, 95% CI 2.9-3.6 cm, p < 0.001) at peak exercise were lower for ASD patients. Exercise assessed peak oxygen uptake was comparable between groups (ASD: 32.8 mL O2/kg/min, 95% CI 30.3-35.5 mL O2/kg/min, controls: 35.2 mL O2/kg/min, 95% CI 31.6-38.8 mL O2/kg/min, p = 0.3). Corrected ASD patients demonstrate a reduced LV and RV systolic exercise response decades after ASD correction whereas resting parameters of LV and RV systolic function were within normal range. The presence of subclinical systolic myocardial dysfunction during exercise might be associated with the long-term morbidities documented in this patient group.

Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study.

Background Despite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD. Methods and Results Thirty-eight corrected patients with isolated secundum ASD and 19 age-matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O2/kg per minute, controls 35.2±7.5 mL O2/kg per minute, P=0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P=0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P=0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P=0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response. Conclusions Patients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long-term risk of atrial fibrillation. Registration Information clinicaltrials.gov. Identifier: NCT03565471.

Sympathovagal imbalance decades after atrial septal defect repair: a long-term follow-up study.

OBJECTIVES: Recent evidence suggests that patients with a corrected atrial septal defect (ASD) have higher morbidity and mortality. An abnormal autonomic regulation of the heart may be a part of the explanation for this. Our objective was to study heart rate variability (HRV) in adults with a corrected ASD as a prominent tool to investigate the autonomic regulation of the heart. METHODS: Autonomic cardiac function was investigated in adults with either a surgically closed or percutaneously closed ASD and healthy control subjects. A 48-h Holter monitor was performed on each participant and HRV was assessed. RESULTS: A total of 17 patients with surgically closed ASDs, 18 percutaneously closed ASDs and 18 controls were included. The mean age in the surgical group, percutaneous group and controls was 32 ± 9, 28 ± 7 and 32 ± 10 years, respectively. The mean time since closure was 19 ± 8 years for the surgical group and 15 ± 5 years for the percutaneous group. The surgically closed ASD patients showed decreased HRV in all six parameters studied when compared to the controls. Similarly, the percutaneously closed ASDs showed decreased HRV in three out of six parameters when compared to controls. CONCLUSIONS: Adults with an ASD, whether closed surgically or percutaneously, have impaired HRV compared to their age- and sex-matched controls, more so in the patients with a surgically closed ASD. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT03565471).

Pacemaker and conduction disturbances in patients with atrial septal defect.

OBJECTIVE: To determine the prevalence of pacemaker and conduction disturbances in patients with atrial septal defects. DESIGN: All patients with an atrial septal defect born before 1994 were identified in the Danish National Patient Registry, and 297 patients were analysed for atrioventricular block, bradycardia, right bundle branch block, left anterior fascicular block, left posterior fascicular block, pacemaker, and mortality. Our results were compared with pre-existing data from a healthy background population. Further, outcomes were compared between patients with open atrial septal defects and atrial septal defects closed by surgery or transcatheter. RESULTS: Most frequent findings were incomplete right bundle branch block (40.1%), left anterior fascicular block (3.7%), atrioventricular block (3.7%), and pacemaker (3.7%). Average age at pacemaker implantation was 32 years. Patients with defects closed surgically or by transcatheter had an increased prevalence of atrioventricular block (p < 0.01), incomplete right bundle branch block (p < 0.01), and left anterior fascicular block (p = 0.02) when compared to patients with unclosed atrial septal defects. At age above 25 years, there was a considerably higher prevalence of atrioventricular block (9.4% versus 0.1%) and complete right bundle branch block (1.9% versus 0.4%) when compared to the background cohorts. CONCLUSIONS: Patients with atrial septal defects have a considerably higher prevalence of conduction abnormalities when compared to the background population. Patients with surgically or transcatheter closed atrial septal defects demonstrated a higher demand for pacemaker and a higher prevalence of atrioventricular block, incomplete right bundle branch block, and left anterior fascicular block when compared to patients with unclosed atrial septal defects.

Influence of Mitroflow bioprosthesis structural valve deterioration on cardiac morbidity.

BACKGROUND: This study investigated the extent and nature of cardiac morbidity and cause of mortality in patients with Mitroflow structural valve deterioration (SVD). METHODS: A retrospective study was performed examining the medical records of patients who had received Mitroflow bioprosthesis between February 2001 and April 2014 and died during this period. A total of 211 patients were identified and included in the analyses. To determine the cause of mortality, cases were divided into three predefined groups: cardiovascular death due to SVD (group 1), cardiovascular death with no SVD (group 2) and non-cardiovascular death without SVD (group 3). RESULTS: Overall mortality in this study was 7.6% at 1 year, 46.4% at 5 years and 97.2% at 10 years. In group 1, 53 patients (25%) died; in group 2, 59 patients (28%) died; and in group 3, 99 patients (47%) died. Hospitalisation for congestive heart failure was observed in 49.1% in the SVD group vs. 10.2 and 13.1% in the two other groups, p < 0.001. Hospitalisation for endocarditis was also significantly higher in the SVD group (11.3%) than in the two other groups (6.8 and 0%), p < 0.05. Hospitalisation due to myocardial infarction, cerebral stroke, arrhythmia or other cardiac-related diseases was not significantly different between groups. CONCLUSION: Structural valve deterioration in Mitroflow bioprosthesis was associated with a high prevalence of hospital admissions due to congestive heart failure and endocarditis. Patients with Mitroflow bioprosthesis should be systematically and routinely followed with echocardiography, and reoperation should be considered if SVD has developed.

Lifelong burden of small unrepaired atrial septal defect: Results from the Danish National Patient Registry.

BACKGROUND: Adult patients with small, unrepaired atrial septal defects (ASD) have higher late mortality than the background population. In this nationwide study, we characterize the late natural history of adults with small, unrepaired ASD. METHODS: Using the Danish National Patient Registry, we included all Danish patients, diagnosed between 1953 and 2011 with an unrepaired ASD. Additionally, all patients, aged 18-65, were invited for clinical testing. Patients also completed a general health survey for comparison with the general population. RESULTS: We identified 723 patients with a small unrepaired ASD. Since the time of diagnosis, 182 patients had died, with an average lifespan of 63 years. The most common cause of death was heart failure. Furthermore, ASD patients had a higher burden of chronic disease than the general population (38.2% vs. 26.9%; p = 0.005), particularly lung disease (3.6% vs. 0.9%; p = 0.008). A total of 153 patients (mean age 32 y) underwent additional testing. On echocardiography an open defect was verified in 19.6% (n = 30) of the patients, of which half subsequently underwent intervention. Interestingly, 6-minute walking distance was markedly reduced (p < 0.0001 compared to normative values) no matter whether the defect was open or closed by echocardiography. Finally, 25.5% of the patients often felt stressed or nervous as compared with 16.3% of the general population (p = 0.004). CONCLUSIONS: Patients with small, unrepaired ASD in adult life have reduced lifespan, more chronic diseases, impaired submaximal exercise capacity, and higher levels of stress than the general population. The current guidelines for intervention and follow-up may need to be reconsidered.

Long-term mortality in patients with atrial septal defect: a nationwide cohort-study.

Aims: In this nationwide cohort of atrial septal defect (ASD) patients, the largest to date, we report the longest follow-up time with and without closure in childhood and adulthood compared with a general population cohort. Methods and results: Using population-based registries, we included Danish individuals born before 1994 who received an ASD diagnosis between 1959 and 2013. All diagnoses were subsequently validated (n = 2277). Using the Kaplan-Meier estimates and Cox proportional hazards regression adjusted for sex, birth year, and a modified Charlson Comorbidity Index, we compared the mortality of ASD patients with that of a birth year and sex matched general population cohort. The median follow-up from ASD diagnosis was 18.1 years (range 1-53 years). Patients with ASD had a higher mortality [adjusted hazard ratio (HR): 1.7; 95% confidence interval (CI): 1.5-1.9] compared with the general population cohort. The adjusted HR 30 days after closure was 1.4 (95% CI: 1.2-1.7), and it was 2.4 (95% CI: 2.0-2.9) for patients without closure. Conclusion: Overall, ASD patients had a higher long-term mortality than a general population cohort matched on birth year and gender. Our data indicate a lower relative mortality of those ASD patients undergoing closure than the ASD patients not undergoing closure.

Long-Term Risk of Atrial Fibrillation and Stroke in Patients With Atrial Septal Defect Diagnosed in Childhood.

The aim of this study was to evaluate the long-term risk of atrial fibrillation (AF) and stroke in patients with atrial septal defect (ASD) diagnosed before the age of 18 years. Patients diagnosed with ASD from 1963 to 2011 were identified through national Danish registers, of which 1,111 fulfilled the inclusion criteria. Each patient was matched with 10 control subjects on age and gender. Risk of AF and stroke was assessed using Cox proportional hazards regression. Cumulative incidences were calculated using Fine and Gray competing risk regression. Median follow-up time was 24 years (range 1 to 49 years). Patients with ASD had a significantly increased risk of AF; both with closure (adjusted hazard ratio [HR] 18.5, 95% confidence interval [CI] 7.8 to 44.1, p <0.0001) and without closure (HR 16.4, 95% CI 6.8 to 39.8, p <0.0001) were compared with control subjects. A comparison of surgical closure with transcatheter closure showed no difference in risk of AF (HR 1.1, 95% CI 0.3 to 4.8, p = 0.864). Risk of stroke was increased in patients with ASD closure (adjusted HR 5.0, 95% CI 2.3 to 11.1, p <0.0001) compared to the control subjects. The use of anticoagulants was increased in patients with ASD regardless of closure (adjusted HR 7.7, 95% CI 4.9 to 12.1, p <0.0001 with closure and HR 4.0, 95% CI 1.9 to 8.7, p <0.0001 without closure). Usage of antiarrhythmic drugs was significantly increased in patients with ASD with closure (adjusted HR 14.8, 95% CI 7.2 to 30.2, p <0.0001). In conclusion, patients diagnosed with an ASD before the age of 18 years had an increased risk of AF in adulthood compared to controls. The risk of AF and stroke was increased despite closure in childhood, and method of closure did not affect the risk of developing AF later in life.

Transposition of the great arteries - a phenotype associated with 16p11.2 duplications?

Genetic analyses of patients with transposition of the great arteries have identified rare copy number variations, suggesting that they may be significant to the aetiology of the disease. This paper reports the identification of a 16p11.2 microduplication, a variation that has yet to be reported in association with transposition of the great arteries. The 16p11.2 microduplication is associated with autism spectrum disorder and developmental delay, but with highly variable phenotypic effects. Autism and attention deficit disorders are observed more frequently in children with congenital heart disease than in the general population. Neonatal surgery is proposed as a risk factor, but as yet unidentified genetic abnormalities should also be taken into account. Thus, congenital heart abnormalities may constitute a part of the phenotypic spectrum associated with duplications at 16p11.2. We suggest chromosomal microarray be considered part of the diagnostic work-up in patients with transposition of the great arteries.