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Ventricular septal defects (VSDs) occur in 1.5-3.5 of 1000 live births and constitutes 20 % of congenital cardiac defects. There is no gender predominance.

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d-Transposition of the great arteries (d-TGA) is the most common form of congenital heart disease that presents with cyanosis in a newborn. The aorta arises from the right ventricle and the pulmonary artery arises from the left ventricle. It constitutes 3-5% of all congenital heart defects. In a simple d-TGA (about two-thirds of patients), there is no other cardiac abnormality other than a patent foramen ovale (PFO) and a patent ductus arteriosus (PDA). In a complex d-TGA additional cardiac abnormalities such as VSD, pulmonary stenosis or coronary abnormalities are present. About one-third to 40% of patients with d-TGA have an associated ventricular septal defect. Among patients with d-TGA, 6% of those with intact ventricular septum and 31% of those with ventricular septal defect have associated pulmonary stenosis. Coronary abnormalities are of importance with regard to the complexity of surgical repair.

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Ventricular septal defects are a rare complication after acute myocardial infarction with a mortality close to 100% if left untreated. However, even surgical or interventional closure is associated with a very high mortality and currently no randomized controlled trials are available addressing the optimal treatment strategy of this disease. This state-of-the-art review and clinical consensus statement will outline the diagnosis, hemodynamic consequences and treatment strategies of ventricular septal defects complicating acute myocardial infarction with a focus on current available evidence and a focus on major research questions to fill the gap in evidence.

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BACKGROUND: Potential differences in complications and/or long-term outcomes of perimembranous ventricular septal defect (pmVSD) closures with 3-mm waist vs. 4-mm waist double-disk symmetrical occluders are not known. METHODS AND RESULTS: A total of 395 consecutive pediatric patients with pmVSD recruited between January 2017 and March 2021 underwent successful transcatheter closure using symmetrical pmVSD devices. The final analysis involved 208×3-mm and 172×4-mm cases. The median follow-up was 42 months (range: 12-62 months). A total of 175 post-procedure adverse events (AEs) were observed. Most of these AEs were temporary, and there were only 8 major AEs. Compared to the 3-mm waist group, the incidence of residual shunts was significantly higher in the 4-mm waist group (13.4% vs. 6.7%; P=0.030), whereas other AEs showed similar incidences between the 2 groups. Multivariate Cox regression analysis revealed that larger defect, higher ratio between device size and body surface area, and longer procedure time can cause an increased likelihood of AEs, and smaller defect or left disk placement within aneurysmal tissue may reduce it. CONCLUSIONS: Transcatheter closure of pmVSD using a symmetrical double-disk occluder is safe and effective. Compared with a 3-mm waist symmetrical occluder, transcatheter closure with a 4-mm waist symmetrical occluder correlated with higher incidences of residual shunts.

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BACKGROUND: Postinfarct ventricular septal rupture is a serious complication in delayed or failed reperfusion with a grim prognosis. The optimal timing and treatment option remain debatable in the absence of randomized controlled trials. Percutaneous device closure is a well-reported and less invasive treatment option but recent imaging studies indicate that majority of defects are too large to be adequately covered by the currently Conformite Europeenne and Food and Drug Administration approved occluder devices. METHODS: Six patients presented with large and complex postinfarct ventricular septal ruptures, considered unsuitable for the Amplatzer post-infarct ventricular septal defect Occluder, so were treated using the prototype Occlutech® 36 mm PI-VSD occluder, including the first-in-human use. RESULTS: The prototype device was successfully deployed in all patients with satisfactory immediate results and shunt reduction. Three patients (50%) in cardiogenic shock did not survive beyond discharge, of which two were complicated by device dislodgement or embolization. CONCLUSIONS: Percutaneous closure of large postinfarct ventricular septal ruptures is possible using newer device with a wider coverage. Further device refinement is necessary to improve treatment outcomes.

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Percutaneous closure of ventricular septal defect (VSD) can effectively occlude abnormal blood flow between ventricles. However, commonly used Nitinol occlusion devices have non-negligible limitations, such as nondegradability leading to life-threatening embolization; limited device size predisposing to displacement and wear; only a few radiopaque markers resulting in inaccurate positioning. Nevertheless, the exploration of customized, biodegradable, and overall radiopaque occluders is still vacant. Here, overall radiopaque, biodegradable, and dynamic reconfigurable 4D printed VSD occluders are developed. Based on wavy bionic structures, various VSD occluders are designed and manufactured to adapt to the position diversity of VSD. The customized configuration, biocompatibility, and biodegradability of the developed 4D printed bionic occluders can eliminate the series of complications caused by traditional occluders. The overall radiopacity of 4D printed VSD occluders is validated ex vivo and in vivo, whereby accurate positioning can be assured. Notably, the preparation strategies for 4D printed occluders are scalable, eliminating the barriers to mass production, and marking a meaningful step in bridging the gap between modeling and clinical application of 4D printed occlusion devices. This work opens attractive perspectives for the rapid manufacturing of customized intelligent medical devices for which overall radiopacity, dynamic reconfigurability, biocompatibility, and biodegradability are sought.

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BACKGROUND: Transcatheter closure of a patent ductus arteriosus in children is widely performed to reduce symptoms and decrease the risk of endocarditis. Most arterial ducts are closed successfully with dedicated devices. However, in a tubular or "type C" patent ductus arteriosus with congestive heart failure, the occlusion is more challenging with these devices, with a higher risk of complications, such as aortic or left pulmonary stenosis and device embolization. AIM: To report our experience with muscular ventricular septal defect devices for patent ductus arteriosus occlusion in small children. METHODS: Retrospective observational series of patients weighing<10kg, with a tubular patent ductus arteriosus (typeC) and congestive heart failure, who underwent transcatheter closure with a muscular ventricular septal defect device between 2017 and 2019. RESULTS: Eight patients were included. The mean age and weight at closure were 6.3 months (range 1-18 months) and 5.3kg (range 2.4-8.2kg), respectively. All patent ductus arteriosus were occluded successfully using Occlutech® (N=3) or Amplatzer® (N=5) muscular ventricular septal defect devices. In four cases, the muscular ventricular septal defect device was used after failure to close the patent ductus arteriosus with a dedicated patent ductus arteriosus device. Two patients had mild left pulmonary artery stenosis, with a maximum velocity on continuous Doppler of 3m/s and 2.7m/s, respectively. After a mean follow-up of 28 months (range 14-41 months), all patients were asymptomatic with excellent results. The mild pulmonary stenosis improved, with a maximum velocity of 2.3m/s in both patients. CONCLUSIONS: Closure of tubular patent ductus arteriosus in small children with congestive heart failure using a muscular ventricular septal defect device is safe in this preliminary experience. Further studies with more patients are warranted.

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Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.

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The purpose of this study was to assess the value of echocardiography for intraoperative guidance during closure of perimembranous ventricular septal defects (pmVSD) and to assess outcomes of these patients. We identified and assessed 78 patients who underwent 2- and 3-dimensional echocardiography-guided mini-invasive per-atrial closure of pmVSD in the cardiac surgery department of our institution, from February 2016 to August 2018, and 76 patients who underwent transcatheter closure of VSD guided by fluoroscopy at the pediatric department (percutaneous control group). All the patients underwent echocardiography. Their clinical data were retrospectively reviewed and analyzed. All patients were followed up using transthoracic echocardiography (TTE) for a maximum of 24 months after the closure. All patients underwent successful device implantation. Echocardiography showed that the major immediate complications included residual shunt, pericardial effusion, and tricuspid regurgitation in the per-atrial group. During the mid-term follow-up period, TTE revealed that the most common complication was tricuspid regurgitation (non-preexisting). There were no cases of VSD recurrence, device displacement, valvular injury, malignant arrhythmias, hemolysis, or death. Moreover, according to the TTE data, the intracardiac structure of the patients were improved. Compared to the control group, the intracardiac manipulation time was shorter and the number of patients with residual shunts, redeployment of devices, or immediate new tricuspid regurgitations was fewer when using 2- and 3-dimensional echocardiography. However, the procedure time in the per-atrial group was slightly longer than that in the control group. Two- and 3-dimensional echocardiography are feasible monitoring tools during mini-invasive per-atrial VSD closure. The short- and mid-term follow-up showed satisfactory results compared to fluoroscopy.

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Postinfarction ventricular septal defect (VSD) is an uncommon but almost lethal complication. The optimal timing for VSD repair is matter of debate, and mechanical circulatory support (MCS) devices allow to hemodynamically support the patient and postpone the VSD closure until myocardial tissue is less friable and the patient's condition is less compromised. However, data are lacking to guide the choice of the best types of MCS in case of VSD. We present a case of a large postinfarction VSD and the use of central venoarterial extracorporeal membrane oxygenation support to stabilize the patient until the VSD surgical repair. This case offers the opportunity to revise the indications and characteristics of different MCS, highlighting pros and cons of each one.

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RATIONALE: To discuss suitable criteria for the application of asymmetric Amplatzer occluders for perimembranous ventricular septal defects (pmVSDs). PATIENTS CONCERNS AND DIAGNOSES: We retrospectively studied 18 children with perimembranous VSDs who underwent attempted asymmetric occluder closure between January 2015 and December 2018 in our center. INTERVENTIONS: Asymmetric Amplatzer occluders were attempted to be placed to all the enrolled patients. We analyzed the diameter of the defects with the receiver operating characteristic curve (ROC) values, the size of the occluders attempted, the presence of aneurysm and the presence of aortic valve prolapse for each patient. Then, for patients who experienced successful device implantation, the therapeutic efficiency was evaluated by follow-up. OUTCOMES: Only 5 out of a total of 18 patients completed successful device implantation. Compared with failed cases, successful cases demonstrated a significantly smaller VSD size (5.46 ±â€Š1.03 mm vs. 8.73 ±â€Š2.33 mm, P = 0.012) and had a low ratio of aortic valvar prolapse (20% vs. 76.92%, P = 0.026). Four out of 5 successful cases involved arrhythmia complications, but the rhythm of the heart recovered after drug treatment. According to the ROC and Youden analyses, the cut-off value of the defect size for successful asymmetric Amplatzer occluder implantation was no larger than 5.7 mm. LESSONS: The application of an asymmetric Amplatzer occluder expands the range of indications for patients with superior localized VSD but is largely limited in cases with aortic valvar prolapse and large VSD sizes. All successful cases recovered from arrhythmia postprocedure.

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BACKGROUND: Transcatheter ventricular septal defect (VSD) closure is a safe and efficacious alternative to surgery. However, its benefits in asymptomatic or minimally symptomatic patients remain unknown. METHODS: Sixty patients with VSD aged 12 to 60 years underwent cardiopulmonary exercise test and echocardiography 1 day before transcatheter VSD closure and 6 months after intervention (closure group). Thirty patients who did not receive the intervention underwent the same evaluations over 6 months (observation group). RESULTS: No significant change in exercise function was observed after VSD closure, except for increased peak oxygen (O2) pulse (absolute increase: 0.4±1.4 mL/beat). Left ventricular end-diastolic dimension and mitral peak early filling velocity-to-early diastolic annular velocity ratio decreased (absolute decrease: 0.3±0.6 cm and 0.7±1.9, respectively). Despite unchanged overall peak O2 consumption, 33% of closure group patients exhibited clinically significant improvements in peak O2 consumption (>10% increase relative to baseline). This was not related to the pulmonary flow-to-systemic flow ratio or baseline exercise capacity. By contrast, all exercise function parameters deteriorated significantly in the observation group. Subgroup analysis revealed that patients with a baseline left ventricular end-diastolic dimension Z score of >2 exhibited a significantly greater improvement in peak O2 consumption, peak O2 pulse, and oxygen uptake efficiency slope than did the observation group. CONCLUSIONS: Compared with conservative management, transcatheter VSD closure prevents deterioration in exercise capacity and promotes left ventricular reverse remodeling in asymptomatic or minimally symptomatic patients. These benefits are most prominent in patients whose left ventricular end-diastolic dimension Z score before intervention is >2, irrespective of baseline peak O2 consumption and pulmonary flow/systemic flow ratio. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03127748.

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BACKGROUND: Outcome data of doubly committed subarterial ventricular septal defect closure in adults are limited. METHODS: A review was made of the inpatients >18 years of age who underwent doubly committed subarterial ventricular septal defect closure between June 2010 and June 2017. RESULTS: The patients were categorised into two groups: The valve intervention group consisted of 31 patients who underwent aortic valvuloplasty, aortic valve replacement, or repair of sinus Valsalva aneurysm in addition to doubly committed subarterial ventricular septal defect closure; non-valvular intervention group comprised 58 patients who underwent only doubly committed subarterial ventricular septal defect closure. The groups did not differ by sex and age. Patients in the valve intervention group, with a larger ventricular septal defect size, were shorter and tended to be lighter. The valve intervention group had more patients with pneumonia perioperatively. No infective endocarditis and reoperation were noted during the study period. At last follow-up, 91 and 96.6% of the studied patients were free from left ventricle dilation and pulmonary hypertension. In patients without pre-operative aortic regurgitation, 12 developed new mild aortic regurgitation during the follow-up. CONCLUSIONS: About 34.8% of adult patients with doubly committed subarterial ventricular septal defect required concurrent intervention on aortic valve or sinus Valsalva aneurysm. The midterm results of doubly committed subarterial ventricular septal defect closure in adult patients were favourable. However, the incidence of new mild aortic regurgitation after ventricular septal defect closure was high (27.3%). Long-term follow-up of aortic regurgitation progression is needed.

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To identify suitable cases and reduce failure/complication rates for percutaneous ventricular septal defect (VSD) closure, we aimed to (1) study causes of device failure and (2) compare outcomes with different VSD types and devices in a high-volume single center with limited resources. Retrospective data of 412 elective percutaneous VSD closure of isolated congenital VSDs between 2003 and 2017 were analyzed. Out of 412, 363 were successfully implanted, in 30 device implantation failed, and in 19 the procedure was abandoned. Outcome was assessed using echocardiography, electrocardiography, and catheterization data (before procedure, immediately after and during follow-up). Logistic regression analyses were performed to assess effects of age, VSD type, and device type and size on procedural outcome. Median [interquartile range] age and body surface area were 6.6 [4.1-10.9] years and 0.7 [0.5-1.0] m2, respectively. Device failure was not associated with age (p = 0.08), type of VSD (p = 0.5), device type (p = 0.2), or device size (p = 0.1). Device failure occurred in 7.6% of patients. As device type is not related to failure rate and device failure and complication risk was not associated with age, it is justifiable to use financially beneficial ductal devices in VSD position and to consider closure of VSD with device in clinically indicated children.

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