Therapy For Congenital Heart Disease Research Articles

Transcriptome studies of congenital heart diseases: identifying current gaps and therapeutic frontiers.

Congenital heart disease (CHD) are genetically complex and comprise a wide range of structural defects that often predispose to - early heart failure, a common cause of neonatal morbidity and mortality. Transcriptome studies of CHD in human pediatric patients indicated a broad spectrum of diverse molecular signatures across various types of CHD. In order to advance research on congenital heart diseases (CHDs), we conducted a detailed review of transcriptome studies on this topic. Our analysis identified gaps in the literature, with a particular focus on the cardiac transcriptome signatures found in various biological specimens across different types of CHDs. In addition to translational studies involving human subjects, we also examined transcriptomic analyses of CHDs in a range of model systems, including iPSCs and animal models. We concluded that RNA-seq technology has revolutionized medical research and many of the discoveries from CHD transcriptome studies draw attention to biological pathways that concurrently open the door to a better understanding of cardiac development and related therapeutic avenue. While some crucial impediments to perfectly studying CHDs in this context remain obtaining pediatric cardiac tissue samples, phenotypic variation, and the lack of anatomical/spatial context with model systems. Combining model systems, RNA-seq technology, and integrating algorithms for analyzing transcriptomic data at both single-cell and high throughput spatial resolution is expected to continue uncovering unique biological pathways that are perturbed in CHDs, thus facilitating the development of novel therapy for congenital heart disease.

Outcomes of cardiac resynchronization therapy in congenital heart disease: A meta-analysis and systematic review.

Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure with reduced ejection fraction. However, there is still a gap of evidence in congenital heart disease (CHD) patients regarding resynchronization therapy. We performed a meta-analysis and systematic review of CHD patients who received CRT implantation. We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to June 2023. Studies that reported response rate to CRT, total mortality rate, change in QRS duration, change in left ventricular ejection fraction, and change in New York Heart Association functional class were included. A total of 14 studies were included in the study. There were 10 studies that reported response rates after implantation. The overall response rate to CRT in CHD patients was 68% (95% confidence interval [CI] 61%-75%, I2 32%). The response rates in patients with systemic right ventricle (RV), systemic left ventricle (LV), and single ventricle were 58% (95% CI 46%-70%, I2 0%), 80% (95% CI 74%-86% I2 14%), and 67% (95% CI 49%-80% I2 0%). Response to CRT in systemic RV was inferior to systemic LV with an odds ratio of 0.38 (95% CI 0.15-0.95, I2 38%). The total mortality rate from sevenstudies was 12% (95% CI 8%-18%, I2 55%). The parameters which represented ventricular dyssynchrony improved after CRT implantation. The overall response rate to CRT in CHD was 68%. Patients with systemic RV had a lower response rate to CRT when compared to patients with systemic LV. The total mortality rate after CRT implantation was 12%.

Comparative observation of changes in natriuretic peptides before and after interventional therapy for congenital heart disease

OBJECTIVE: To explore changes in the plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with left-to-right shunt congenital heart disease (CHD) before and in the early stage after interventional occlusion and to evaluate the clinical significance. METHODS: Among 97 patients with left-to-right shunt CHD undergoing interventional occlusion, 34 cases had a VSD (ventricular septal defect), 35 cases had an ASD (atrial septal defect), and 28 cases had PDA (patent ductus arteriosus). Another 20 normal adults formed the control group. An ELISA was used to determine the plasma ANP and BNP levels before and on the third day after the operation to evaluate their correlations with cardiac functions and the defect size. RESULTS: The plasma ANP and BNP levels of patients with left-to-right shunt CHD were increased compared with those of the normal control group (P< 0.01), and the plasma ANP and BNP levels were decreased on the third day after interventional occlusion compared with the preoperative levels (P< 0.05). The plasma ANP and BNP levels were correlated with the New York Heart Association (NYHA) grade, left ventricular ejection fraction and defect diameter (P< 0.05). CONCLUSION: Patients with left-to-right congenital heart disease exhibit activation of ANP and BNP, which can be alleviated in the early stage after intervention occlusion. Left-to-right shunt congenital heart disease is given priority over atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Early traditional methods included repair or correction by open heart surgery under extracorporeal circulation (also known as cardiopulmonary bypass, CPB). However, interventional therapy has become a developing trend for the treatment of congenital heart disease since 1967, when Porstmann et al. [1]. reported the transcatheter closure of ASD for the first time. The application of the AMPLATZER occluder, which is a simple and feasible method, has improved the safety of the treatment and enabled the therapeutic effect to reach ideal levels. The natriuretic peptide (NP) family consists of the atrial natriuretic polypeptide (ANP), the brain natriuretic peptide, which is also known as the B type natriuretic peptide (BNP), the C type natriuretic peptide (CNP), the renal natriuretic peptide (RNP) and the D type natriuretic peptide (DNP). These family members are similar in structure, have strong natriuretic, diuretic and vasodilative effects and antagonize the activity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nerve. Together, the natriuretic peptides sensitively and specifically reflect the ventricular function state. Although all types of congenital heart disease differ in anatomical structure, they all contain the common features of heart failure. This study detected changes in the serum ANP and BNP levels in patients with left-to-right shunt congenital heart disease before and on the third day after interventional occlusion to evaluate the early changes in left-to-right shunt congenital heart disease after interventional occlusion through neuroendocrine.

Combined subcutaneous implantable cardioverter defibrillator and pacemaker devices in complex congenital heart disease: a single-center experienced based study.

Subcutaneous implantable cardioverter defibrillators (S-ICD) are widely accepted therapy in congenital heart disease (CHD) patients at risk of life-threatening ventricular arrhythmias or sudden cardiac death (SCD) when pacing is not required. Occasionally, pacemaker (PM)-dependent CHD patients will subsequently develop an indication for a cardioverter defibrillator. The use of S-ICD in complex CHD patients who have had already PM devices implanted implies some specific considerations, as the safety for these patients in unknown and recommendations among physicians may vary widely. We review the data and studied the indications for S-ICD in complex CHD with previous PM and discuss its usefulness in clinical practice. From a large cohort of 345 patients enrolled in the S-ICD Monaldi care registry, which encompass all the patients implanted in the Monaldi Hospital of Naples, we considered 11 consecutive complex CHD patients (10M/1F aged 40.4 ±18.4 years) who underwent S-ICD implant after a previous PM implant, from February 2015 to October 2022. Mean follow-up was 25.5 ± 22 months. All the patients showed a good compliance to the device system with no complications (infections or skin erosions). In complex CHD with already implanted PM devices, S-ICD implant appears to be a safe alternative to PM upgrading to transvenous ICD system, avoiding abandoned leads or life-threatening lead extraction. However, there are important issues with regard to testing and programming that need to be addressed at the time of implantation.

Bioresorbable PPDO sliding-lock stents with optimized FDM parameters for congenital heart disease treatment

Stent implantation has been a promising therapy for congenital heart disease (CHD) due to better efficacy. Compared to permanent metal stents, bioresorbable polymer stents have shown a great advantage in accommodating the vascular growth of pediatric patients, but the application is still limited due to inferior radial strength. Here, bioresorbable poly(p-dioxanone) (PPDO) sliding-lock stents for CHD treatment were fabricated by fused deposition modeling (FDM). The effects of FDM processing parameters, including nozzle temperature, bed temperature, layer thickness, and printing speed, on the mechanical properties of PPDO parts were investigated to optimize the processing condition to enhance the radial strength of stents. Finite element analysis (FEA) was also used to evaluate the mechanical properties of stents. PPDO sliding-lock stents fabricated under optimized FDM parameters showed radial strength of 3.315 ± 0.590 N/mm, superior to benchmark commercial metal stents. Radial strength curve and compression behavior of PPDO sliding-lock stents were investigated. Results of FEA exhibited that strut width, shape of the mesh cell and surface coverage ratio had an impact on the compression force of PPDO sliding-lock stents. PPDO sliding-lock stents fabricated with optimized FDM parameters show favorable mechanical performance and meet the requirement of CHD treatment.

Nursing Effect of Comfort Nursing Intervention in Interventional Therapy of Congenital Heart Disease in Children

Nursing Effect of Comfort Nursing Intervention in Interventional Therapy of Congenital Heart Disease in Children

Subcutaneous implantable cardioverter defibrillator in complex adult congenital heart disease. Results from the S-ICD “Monaldi Care” registry

BackgroundImplantable cardioverter defibrillators (ICD) are widely accepted therapy in congenital heart disease (CHD) patients at risk of life-threatening ventricular arrhythmias or sudden cardiac death (SCD). Initial experience with subcutaneous ICD (S-ICD) systems has shown a high efficacy. However, the use of S-ICD in complex ACHD (adult congenital heart disease) implies some specific considerations, as the safety for these patients in unknown and recommendations among physicians may vary widely. MethodsWe review the data and studied the indications for S-ICD in complex ACHD and discuss its usefulness in clinical practice. ResultsFrom a large cohort of 297 patients enrolled in the S-ICD “Monaldi care” registry, that encompass all the patients implanted in the Monaldi Hospital of Naples, we considered 14 consecutive complex ACHD patients (aged 35.9 ± 16.7 years) who underwent S-ICD implant from February 2015 to June 2020. Mean follow-up was 23 ± 19.5 months. All the patients showed a good compliance to the device system with no complications (infections or skin erosions). Four patients (1 M/3F aged 38.2 ± 11.3) were listed for heart transplantation (HTX). Two of these underwent HTX, one died for refractory heart failure (HF) and one is still on the waiting list. ConclusionsThere might be a conceivable benefit from an extended use of the S-ICD in selected patients with CHD, especially in those with life-treating ventricular arrhythmias and complex anatomy or patients awaiting HTX. S-ICD appears to be a safe alternative to a transvenous system when a transvenous ICD cannot be implanted and pacing is not required.

Progress in interventional treatment of children with congenital heart disease

The interventional treatment of congenital heart diseases has been developed for more than 50 years since Rashkind et al.performed balloon atrial septostomy in 1966.From the initial catheter examination and palliative operation to the current radical occlusion, stent implantation, valve replacement, etc, interventional catheterization has become one of main means of treating congenital heart disease.The interventional therapy of congenital heart disease in China has made great progress, but there is still a certain gap with developed countries.This article summarizes the progress of interventional treatments in septal defect diseases, aortic artery to pulmonary artery shunt diseases, valvular diseases, and hybrid therapy, in order to provide reference for the interventional treatment of congenital heart disease in China. Key words: Congenital heart disease; Interventional treatment; Child

Efficacy of different analgesic or sedative drug therapies in pediatric patients with congenital heart disease undergoing surgery: a network meta-analysis.

Surgery is an effective therapy for congenital heart disease (CHD) and the management after surgery poses challenges for the clinical workers. We performed this network meta-analysis to enhance the corresponding evidence with respect to the relative efficacy of different drug treatments applied after the CHD surgery. Embase and PubMed were systematically retrieved to identify all published controlled trials investigating the effectiveness of drugs for patients up to 25 August, 2018. Mean differences (MD), odds ratios and their 95% credible intervals (CrIs) were used to evaluate multi-aspect comparisons. Surface under cumulative ranking curve (SUCRA) was used to analyze the relative ranking of different treatments in each endpoint. Compared to saline, all the drugs achieved better preference under the efficacy endpoints except fentanyl in JET. As for ventilator time, all drugs were more effective than saline while only the difference of dexmedetomidine was statistically obvious (MD = 6.92, 95% CrIs 1.77-12.54). Under the endpoint of ICU time, dexmedetomidine was superior to saline as well (MD = 1.26, 95% CrIs 0.11-2.45). When all the endpoints were taken into consideration and with the help of ranking probabilities and SUCRA values, fentanyl combined with dexmedetomidine was one of the recommended drugs due to its shorter time on ventilator and stay in hospital as well as lower mortality. Overall, based on the comprehensive consideration of all the endpoints, fentanyl combined with dexmedetomidine was considered to be the best-recommended clinical interventions among all the methods.

Development of Continuous-Flow Total Artificial Heart for Use in Infants

Purpose Heart transplantation in infants and children is an accepted therapy for congenital heart disease, but donor organ availability remains unstable. Mechanical circulatory support is another standard option, but there is a lack of implantable devices due to size and functional range. The purpose of this study was to evaluate in vivo performance of the initial prototype of an infant continuous-flow total artificial heart (I-CFTAH) with one motor and one rotating assembly supported by a hydrodynamic bearing. Methods The I-CFTAH was designed to cover a range of 3 kg infant to 9 kg child (flange diameter - 26.9 mm; length - 44 mm), with nominal design point was matched to a 6 kg child, requiring 1.0 L/min of flow. I-CFTAH was tested using in silico virtual simulation mock loop (VML; MATLAB; MathWorks®) and simulated the hemodynamics as they surge through the system implanted with blood pump (run at 0.5 L/min for 3 kg infant). Lumped-parameter model including systemic/pulmonary circulation, values for impedance, beat rate, and blood volume was used. Results The in silico experiments showed intended performance of scaled down pump (left and right pump flows - 0.5 L/min at 4380 RPM). The difference between the left and right atrial pressures was maintained within ± 5-15 mm Hg. Simulation of I-CFTAH was successfully performed and allowed creating arterial pulsation with this device. Conclusion The present simulation-based approach showed feasibility of I-CFTAH design. The I-CFTAH met the proposed requirements for self-regulation, performance and pulse modulation. Further in vitro validation and in vivo implantation will be necessary to explore this technology in more detail.

Cardiac Resynchronization Therapy in Congenital Heart Disease and Pediatric Patients with Heart Failure is Associated with Improved Survival

Purpose Cardiac resynchronization therapy (CRT) has been shown to shorten QRS duration (QRSd) and improve ejection fraction (EF) in adults with congenital heart disease (ACHD) and children with heart failure with reduced ejection fraction (HFrEF). It is not known whether CRT confers a survival benefit. We sought to determine whether CRT is associated with longer transplant-free survival after adjusting for patient factors. Methods All eligible patients ( 3) who received CRT were compared to a propensity score (PS)-matched cohort with similar characteristics at a single center between 2004 and 2017. Controls were identified from non-selective echocardiographic and ECG databases, with enrollment timed to first out-patient visit where all criteria were achieved (no CRT, EF 3). Primary endpoint was transplant-free survival. Results Of 128 patients who underwent CRT, 74 met all study inclusion criteria. 123 non-CRT controls met all inclusion criteria. Controls were younger with higher EF, but fewer had biventricular circulation. For the PS-matched cohorts (n=58 pairs), there were no differences in baseline characteristics (Table 1). Median follow-up was 2.3 years; risk of death or transplant was higher in the control group (HR 0.26 (95% CI 0.15-0.46), p Conclusion For ACHD patients and children with HFrEF, those receiving CRT had longer transplant-free survival and greater freedom from HF rehospitalization.

Cardiac resynchronization therapy in congenital heart disease: Results from the German National Register for Congenital Heart Defects

BackgroundCardiac resynchronization therapy (CRT) is an established option for patients with heart failure. Limited data exists on indications and outcome of CRT in contemporary congenital heart disease (CHD) patients. Methods and resultsAll patients with CRT registered in the German National Register for Congenital Heart Defects were systematically identified. We analysed data on demographics, type of congenital defect as well as repair, associated conditions, indication for CRT, heart failure medication, combination with a defibrillator or pacemaker and outcome. Overall, 65 patients with CRT were identified. The most common congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected transposition of the great arteries (ccTGA) (n = 9) and double outlet right ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional antibradycardia pacing or ICD indications. Of these, the majority (n = 44) underwent an upgrade to a CRT system to avoid the detrimental consequences of longstanding conventional ventricular single-site pacing, whereas four patients required an ICD due to heart failure and a history of malignant ventricular tachycardia. During a median follow-up of 6.9 years 19 patients developed complications: 16 patients experienced pacemaker lead dysfunction and 3 patients pacemaker infection. ConclusionsThe current study based on a large national register for CHD shows that CRT is feasible and can be used as an adjunct in the heart failure treatment of selected CHD patients. Uptake of this therapy proved to be low in this nationwide study and CRT implantation was largely used in patients with a pre-existing pacing indication or those requiring an ICD.

Dilating and fracturing side struts of open cell stents frequently used in pediatric cardiac interventions-An in vitro study.

BackgroundOpen cell stents are frequently used in interventional therapy of congenital heart disease. Overstenting of vessel branches may necessitate strut dilation.Methods and ResultsThe strut size achievable in Bard Valeo and Cook Formula stents, and the pressure necessary to fracture struts was assessed. In addition, a self expanding stent (Optimed SinusflexDS) was also tested. With the original balloon at nominal pressure, in Valeo stents side struts could be dilated to approximately 90% of the nominal stent diameter, in Formula stents to approximately 80%. With larger high pressure woven balloons, strut size increased to approximately 125% in Valeo stents, and to approximately 105% in the Formula. Strut fracture can connect two adjoining struts. Pressures were dependent on the balloon utilized. Sidestruts of the Sinusflex could lastingly overdilated with large balloons only.ConclusionDilation and overdilation of side struts in open cell stents can be achieved. Dependent on the clinical context, the original balloon used to place the premounted stent can be used to achieve strut dilation, but woven high pressure balloons maybe safer for patients. Should a larger diameter be required, these high pressure woven balloons can achieve bigger diameters and even strut fracture.

New conception of interventional therapy for congenital heart disease in neonates

The main clinical manifestations of neonatal critical and complex congenital heart disease (CHD) are cardiac insufficiency and severe hypoxemia.Because of the rapid development of the CHD, most children will die early.Through the analysis of the successful interventional treatment of some severe CHDs in the neonatal, the indivi-dualized interventional treatment can be used according to different congenital malformations, and the interventional materials, which are different from the pediatric cardiology, are used reasonably.So many interventional therapies before or after surgery were used, and even, replace traditional surgical treatment to cure or palliate the CHD in neonates. Key words: Congenital heart disease; Interventional therapy; Infant, newborn

Maternal hyperoxygenation: A potential therapy for congenital heart disease in the fetuses? A systematic review of the current literature.

To assess efficacy, safety, outcomes, and intrauterine complications following maternal hyperoxygenation (MH) therapy in fetuses with congenital heart disease (CHD). A systematic review was performed following an electronic search of databases. Articles were published before January 1, 2017, in an English-language and non-English-language journals (with English translations), and included human fetuses and expectant mothers with a fetal diagnosis of CHD who received MH. Ninety-six articles were identified; 72 were excluded and 24 full-text articles were reviewed. Only 9 articles met inclusion criteria and were analyzed. A total of 270 fetuses underwent MH therapy: 169 had CHD, and 101 had normal heart anatomies. Seven studies used fetal echocardiography, while 2 studies used cardiac magnetic resonance imaging (CMR). The mean gestational age at therapy was 33.4weeks (26-38weeks). Majority of MH protocols used 100% FiO2 with non-rebreather face mask at 8L of flow, achieving 60%-70% FiO2 , or maternal PaO2 goal of 250mmHg. No significant adverse events were reported. Four studies reported increased size of the hypoplastic cardiac structures after MH. Three studies utilized acute MH to risk stratify hypoplastic left heart syndrome fetuses. Two studies assessed acute MH in the setting of CMR. The current evidence for MH therapy suggests an increase in pulmonary blood flow, and venous return, ductal flow, and heart dimensions in fetuses. MH has potential as a diagnostic and therapeutic tool in fetuses with CHD. Further randomized controlled trials are needed to ascertain whether MH therapy provides improved outcomes on fetuses with certain types of CHD.

P742Use of cardiac resynchronization therapy in congenital heart disease: Results from the German national register for congenital heart defects

P742Use of cardiac resynchronization therapy in congenital heart disease: Results from the German national register for congenital heart defects

Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease.

Percutaneous therapies for congenital heart disease have evolved rapidly in the past 3 decades. This has occurred despite limited investment from industry and support from regulatory bodies resulting in a lack of specific device development. Indeed, many devices remain off-label with a best-fit approach often required, spurning an innovative culture within the subspecialty, which had arguably laid the foundation for many of the current and evolving structural heart interventions. Challenges remain, not least encouraging device design focused on smaller infants and the inevitable consequences of somatic growth. Data collection tools are emerging but remain behind adult cardiology and cardiac surgery and leading to partial blindness as to the longer-term consequences of our interventions. Tail coating on the back of developments in other fields of adult intervention will soon fail to meet the expanding needs for more precise interventions and biological materials. Increasing collaboration with surgical colleagues will require development of dedicated equipment for hybrid interventions aimed at minimizing the longer-term consequences of scar to the heart. Therefore, great challenges remain to ensure that children and adults with congenital heart disease continue to benefit from an exponential growth in minimally invasive interventions and technology. This can only be achieved through a concerted collaborative approach from physicians, industry, academia, and regulatory bodies supporting great innovators to continue the philosophy of thinking beyond the limits that has been the foundation of our specialty for the past 50 years.

The Role of 3-D Echocardiography in Guiding Transcatheter Treatment of Congenital or Structural Heart Disease

With the advancement of new techniques, real-time three-dimensional echocardiography has been used to guide transcatheter therapy of congenital heart disease as well as structural heart disease. The real-time 3-D echocardiography provides visualization of 3-D anatomy and location of the defect and it's adjacent structures. When using this new technology in guiding transcatheter therapy, the interventionalist can visualize the morphology and size of the defects. This allows the interventionalist to select the appropriate type and size of the device to close the defect and guide the procedure. After device deployment, the 3-D ehcocardiography can be used to evaluate the position of the device, presence of residual shunts, and the status of adjacent structures. Therefore, the mean fluoroscopic time can be reduced. The real-time 3-D echocardiography is useful in providing guidance of transcatheter therapy for congenital heart disease and structural heart disease.

Stem cell therapies for congenital heart disease.

Congenital heart disease (CHD) is the most prevalent congenital anomaly in newborn babies. Cardiac malformations have been induced in different animal model experiments, by perturbing some molecules that take part in the developmental pathways associated with myocyte differentiation, specification, or cardiac morphogenesis. The exact epigenetic, environmental, or genetic, basis for these molecules perturbations is yet to be understood. But, scientist have bridged this gap by introducing autologous stem cell into the defective hearts to treat CHD. The choice of stem cells to use has also raised an issue. In this review, we explore different stem cells that have been recently used, as an update into the pool of this knowledge and we suggested the future perspective into the choice of stem cells to control this disease. We propose that isolating mesenchymal stem cells from neonate will give a robust heart regeneration as compared to adults. This source are easily isolated. To unveil stem cell therapy beyond its possibility and safety, further study is required, including largescale randomized, and clinical trials to certify the efficacy of stem cell therapy.

Cardiac resynchronization therapy in congenital heartdisease.

Cardiac resynchronization therapy (CRT) is an established treatment option for adult patients suffering heart failure due to idiopathic or ischemic cardiomyopathy associated with electromechanical dyssynchrony. There is limited evidence suggesting similar efficacy of CRT in patients with congenital heart disease (CHD). Due to the heterogeneity of structural and functional substrates, CRT implantation techniques are different with athoracotomy or hybrid approach prevailing. Efficacy of CRT in CHD seems to depend on the anatomy of the systemic ventricle with best results achieved in systemic left ventricular patients upgraded to CRT from conventional pacing. Indications for CRT in patients with CHD were recently summarized in the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS) Expert Consensus Statement on the Recognition and Management of Arrhythmias in Adult Congenital Heart Disease and are presented in the text.