Time Course of Diastolic and Systolic Function Improvement After Pulmonary Valve Replacement in Adult Patients With Tetralogy of Fallot

ObjectivesThe aim of this research was to assess right ventricular diastolic and systolic function before and after pulmonary valve replacement (PVR) in adult patients after repair of tetralogy of Fallot.BackgroundPulmonary valve replacement (PVR) in adult patients late after repair of tetralogy of Fallot leads to rapid improvement of right ventricular (RV) systolic function.MethodsA total of 16 patients and 8 healthy subjects were included. Median age at initial repair was 4.9 (0.9 to 13.1) years, and mean age at PVR was 28.7 (19.5 to 45.6) years. Cardiac magnetic resonance imaging was performed before and 8 and 22 months after PVR. Right ventricular volumes and function as well as RV in- and outflow patterns were assessed.ResultsThe volume of the early filling of the RV (Evol) increased from 49.8 ± 14.7 ml to 53.8 ± 19.3 ml (not significant) and 62.0 ± 18.9 ml, respectively (p < 0.05), whereas the volume of the atrial contraction (Avol) remained unchanged. Consequently, the Evol/Avol ratio increased from 1.4 ± 0.7 before PVR to 1.6 ± 0.7 at 8 months (not significant) and 2.3 ± 1.2 at 22 months (p < 0.01). The Evol/Avol ratio was not significantly different from the healthy subjects at 22 months, indicating late recovery of diastolic function. Systolic function improved rapidly after PVR; the indexed RV end-systolic volume decreased from 93.7 ± 33.0 ml/m2to 60.9 ± 18.4 ml/m2(p < 0.01) and 54.8 ± 21.0 ml/m2(p < 0.01).ConclusionsIn adult patients late after total repair of Fallot, PVR leads to late improvement of diastolic function. We speculate that the rapid volume unloading after PVR increases systolic performance, whereas improvement in diastolic function requires long-term remodeling

The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease

AimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.Methods and resultsTen patients (70% female, median age 50 years [46.5–52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04–2021 and 01–2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 ± 17 to 97 ± 23 µmol/L, p = 0.036, and 72 ± 14 vs. 66 ± 16 ml/min/1.73m2, p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3–1193.3] to 531.6 [400.8–1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.ConclusionDapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population

Fertility, pregnancy and delivery in women after biventricular repair for double outlet right ventricle

Objectives: To investigate outcome of pregnancy and fertility in women with double outlet right ventricle (DORV). Methods: Using 2 congenital heart disease registries, 21 female patients with DORV (aged 18-39 years) were retrospectively identified. Detailed recordings of each patient and their completed (>20 weeks gestation) pregnancies were recorded. Results: Overall, 10 patients had 19 pregnancies, including 3 spontaneous miscarriages (16%). During the 16 live birth pregnancies, primarily (serious) noncardiac complications were observed, e.g. premature labor/delivery (n = 7 and n = 3, respectively), small for gestational age (n = 4), preeclampsia (n = 2) and recurrence of congenital heart disease (n = 2). Except for postpartum endocarditis and deterioration of subpulmonary obstruction, only mild cardiac complication pregnancies were recorded. Two women with children reported secondary female infertility. Several menstrual cycle disorders were reported: secondary amenorrhea (n = 4), primary amenorrhea (n = 3) and oligomenorrhea (n = 2). Conclusion: Successful pregnancy in women with DORV is possible. Primarily noncardiac complications were observed and only few (minor) cardiac complications. Infertility and menstrual cycle disorders appear to be more prevalent. Copyrigh

Right ventricular peak systolic longitudinal strain is a sensitive marker for right ventricular deterioration in adult patients with tetralogy of Fallot

The aim of this study was to evaluate the feasibility of right ventricular (RV) longitudinal peak systolic strain (LPSS) assessment for the follow-up of adult patients with corrected tetralogy of Fallot (TOF). Adult patients (n = 18) with corrected TOF underwent echocardiography and CMR twice with a time interval of 4.2 ± 1.7 years. RV performance was derived from CMR, and included RV volumes and ejection fraction (EF). LPSS was calculated globally (GLPSS) and in the RV free wall (LPSS FW), with echocardiographic speckle-tracking strain-analysis. Baseline (G)LPSS values were compared between patients and healthy controls; the relation between (G)LPSS and CMR parameters was evaluated and the changes in (G)LPSS and CMR parameters during follow-up were compared. GLPSS and LPSS FW were significantly reduced in patients as compared to controls (−14.9 ± 0.7% vs. −21.6 ± 0.9% and −15.5 ± 0.9% vs. −22.7 ± 1.5%, P < 0.01). Moderate agreement between LPSS and CMR parameters was observed. RV EF remained unchanged during follow-up, whereas GLPSS and LPSS FW demonstrated a significant reduction. RVEF showed a 1% increase, whereas GLPSS decreased by 14%, and LPSS FW by 27%. RV LPSS is reduced in TOF patients as compared to controls; during follow-up RV EF remained unchanged whereas LPSS decreased suggesting that RV LPSS may be a sensitive marker to detect early deterioration in RV performance

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Intra-observer and interobserver variability of biventricular function, volumes and mass in patients with congenital heart disease measured by CMR imaging

Cardiovascular magnetic resonance (CMR) imaging provides highly accurate measurements of biventricular volumes and mass and is frequently used in the follow-up of patients with acquired and congenital heart disease (CHD). Data on reproducibility are limited in patients with CHD, while measurements should be reproducible, since CMR imaging has a main contribution to decision making and timing of (re)interventions. The aim of this study was to assess intra-observer and interobserver variability of biventricular function, volumes and mass in a heterogeneous group of patients with CHD using CMR imaging. Thirty-five patients with CHD (7–62 years) were included in this study. A short axis set was acquired using a steady-state free precession pulse sequence. Intra-observer and interobserver variability was assessed for left ventricular (LV) and right ventricular (RV) volumes, function and mass by calculating the coefficient of variability. Intra-observer variability was between 2.9 and 6.8% and interobserver variability was between 3.9 and 10.2%. Overall, variations were smallest for biventricular end-diastolic volume and highest for biventricular end-systolic volume. Intra-observer and interobserver variability of biventricular parameters assessed by CMR imaging is good for a heterogeneous group of patients with CHD. CMR imaging is an accurate and reproducible method and should allow adequate assessment of changes in ventricular size and global ventricular function

Psychosocial impact of implantable cardioverter defibrillators (ICD) in young adults with Tetralogy of Fallot

Item does not contain fulltextOBJECTIVE: To investigate the psychosocial impact of having an implantable cardioverter defibrillator (ICD) in adults with Tetralogy of Fallot (ToF). METHODS: Included were 26 ToF-patients with an ICD (age 44 +/- 12 years), and two control groups consisting of 28 ToF-patients without an ICD (age 40 +/- 10 years) and a group of 35 ICD-patients of older age without ToF (age 72.0 +/- 8 years). This last control group was chosen to represent the "older general ICD population" with acquired heart disease seen at the out-patient clinic. Psychosocial functioning encompassed daily functioning, subjective health status, quality of life, anxiety, depression, coping and social support. RESULTS: ToF-patients with ICD showed diminished psychosocial functioning in comparison to ToF-patients without ICD. This was reflected by diminished subjectively perceived physical functioning (p = 0.01), general health perception (p < 0.01) and a lower satisfaction with life (p = 0.02). In comparison to older ICD-patients, ToF-patients with ICD showed less satisfaction with life (p = 0.03), experienced more anxiety (p = 0.01) and showed less favourable coping styles, although physical functioning was better for ToF-patients with ICD than for older ICD-patients (p = 0.01). More inappropriate shocks were found in ToF-patients with ICD compared to the older ICD-patients. CONCLUSION: In patients with ToF, ICD implantation had a major impact on psychosocial functioning which should be taken into account when considering ICD implantation in these young patients. To help improve psychosocial functioning, psychological counselling attuned to the specific needs of these patients may be useful.1 juli 201

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus