Targeting the Autophagy-Lysosome Pathway in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure.

The key biological "drivers" that are responsible for reverse left ventricle (LV) remodeling are not well understood. To gain an understanding of the role of the autophagy-lysosome pathway in reverse LV remodeling, we used a pathophysiologically relevant murine model of reversible heart failure, wherein pressure overload by transaortic constriction superimposed on acute coronary artery (myocardial infarction) ligation leads to a heart failure phenotype that is reversible by hemodynamic unloading. Here we show transaortic constriction + myocardial infarction leads to decreased flux through the autophagy-lysosome pathway with the accumulation of damaged proteins and organelles in cardiac myocytes, whereas hemodynamic unloading is associated with restoration of autophagic flux to normal levels with incomplete removal of damaged proteins and organelles in myocytes and reverse LV remodeling, suggesting that restoration of flux is insufficient to completely restore myocardial proteostasis. Enhancing autophagic flux with adeno-associated virus 9-transcription factor EB resulted in more favorable reverse LV remodeling in mice that had undergone hemodynamic unloading, whereas overexpressing transcription factor EB in mice that have not undergone hemodynamic unloading leads to increased mortality, suggesting that the therapeutic outcomes of enhancing autophagic flux will depend on the conditions in which flux is being studied.

Pulmonary artery debanding in the cath lab: Lessons learned!

Background: Although primary definitive repair of congenital heart disease has become the preferred management approach, pulmonary artery banding (PAB) remains a valuable palliative procedure used to restrict pulmonary blood flow in certain conditions. However, when the band is to be removed, another surgical intervention is usually required. Methods: To describe percutaneous removal of pulmonary artery band, the medical records of patients who underwent this procedure were reviewed. Results: Between 2000 and 2020, 143 patients underwent PAB. Of these, we attempted balloon debanding of the pulmonary artery in four patients. At the time of the procedure, the average age of patients was 36 ± 6.24 months, and their average weight was 12.37 kg. Band removal via catheter was successful in three cases and was associated with an adequate reduction in pressure gradient across the pulmonary artery band site (average of 71.67 ± 12.58 to 23.67 ± 2.89 mm Hg). None of the patients experienced complications during or after the procedure. Follow-up data after discharge (3-10 years) provides reassuring and satisfactory results. Conclusion: Based on our findings, we suggest that percutaneous removal of the pulmonary artery band might be a safe and effective alternative to surgical debanding. However, studies with a larger sample are required for further clinical implementation of the technique.

The relationship between miRNA-26b and connective tissue growth factor in rat models of aortic banding and debanding.

BACKGROUND/AIMS: Connective tissue growth factor (CTGF) is a profibrotic factor implicated in pressure overload-mediated myocardial fibrosis. In this study, we determined the role of predicted CTGF-targeting microRNAs (miRNAs) in rat models of aortic stenosis and reverse cardiac remodeling. METHODS: Minimally invasive ascending aortic banding was performed in 24 7-week-old male Sprague-Dawley rats, which were divided into three groups. The banding group consisted of eight rats that were sacrificed immediately after 6 weeks of aortic constriction. The debanding group underwent aortic constriction for 4 weeks and was sacrificed 2 weeks after band removal. The third group underwent sham surgery. We investigated the expression of CTGF, transforming growth factor-ß1 (TGFß1), and matrix metalloproteinase-2 using ELISA and examined miRNA-26b, miRNA-133a, and miRNA-19b as predicted CTGF-targeting miRNAs based on miRNA databases in 24-hour TGFß-stimulated and TGFß- washed fibroblasts and myocardial tissues from all subjects. RESULTS: CTGF was elevated in 24-hour TGFß-stimulated fibroblasts and decreased in 24-hour TGFß-washed fibroblasts. miRNA-26b was significantly increased in TGFß-washed fibroblasts compared with control and TGFß-stimulated fibroblasts (p < 0.05). CTGF expression was significantly higher in the banding group than that in the sham and debanding groups. The relative expression levels of miRNA-26b were higher in the debanding group than in the banding group. CONCLUSION: The results of our study using models of aortic banding and debanding suggested that miRNA-26b was significantly increased after aortic debanding. The in vitro model yielded the same results: miRNA-26b was upregulated after removal of TGFß from fibroblasts.

Percutaneous pulmonary artery debanding.

BACKGROUND: There is a paucity of data on palliative or total percutaneous pulmonary artery debanding (p-debanding), particularly with use of a stent. METHODS: Twelve p-debandings in eight patients were included in this study. Age at pulmonary artery banding (PAB) ranged from 3 days to 1 year (median, 13 days), while p-debanding was performed at 2-157 (7) months. The body weight at the p-debanding ranged from 3.2 to 22.2 (7.3) kg. We chose the balloon diameter of 30-50% to the circumference of the band for palliative, and larger than 50% for total p-debanding, respectively. In either way, the balloon diameter did not exceed 1.5 times the reference vessel diameter. Stent was implanted for palliative p-debanding in 2 patients. RESULTS: 1. The circumference of the band ranged from 16 to 23 (20) mm, while the balloon diameter ranged from 20-60 (40)% to that, where larger than 50% was used for 2 procedures intended total p-debanding. 2. PAB diameter increased from 2.5-4.7 (3.0) mm to 2.8-9.5 (4.5) mm (p<0.01), however, there was no significant change in the diameter in 2 procedures. In one patient, p-debanding was the definitive treatment associated with spontaneous near closure of muscular ventricular septal defect, in another patient of congenitally corrected transposition of the great arteries, severely depressed left ventricular ejection fraction was recovered following p-debanding. 3. Arterial oxygen saturation (SaO2) increased from 64-97 (80)% to 66-95 (90)% (p<0.01), while in 10 procedures of 6 patients where the indication of p-debanding was hypoxia, SaO2 increased in 8 procedures. There was no significant pulmonary hypertension following p-debanding. CONCLUSION: Palliative or total p-debanding using balloon and/or stenting is generally feasible and effective. A balloon diameter 35-50% to the band circumference in palliative, and more than 50% in total p-debanding, while in either way less than 1.5 times the reference vessel diameter, is safe.

Percutaneous pulmonary debanding for an infant complicated by spontaneously closing muscular ventricular septal defect: A case report and in vitro study.

Pulmonary artery banding (PAB) is a standard operation for various congenital heart defects complicated by pulmonary hypertension (PH) and judged unsuitable for primary intracardiac repair. We report successful percutaneous pulmonary artery debanding in a baby complicated by muscular ventricular septal defect (VSD), that was initially large and multiple, but closed spontaneously later. The 5-month-old boy was referred to our hospital on day 3, diagnosed as having aortic coarctation (CoA), with multiple muscular VSDs and severe PH. On day 6, he underwent CoA repair and PAB using expanded polytetrafluoroethylene (ePTFE), while the muscular VSDs were left open. We planned percutaneous pulmonary debanding at the age of 5 months, as the muscular VSDs had become small. After dilation with a Mustang® (Boston Scientific, Marlborough, Massachusetts, United State) balloon (12 mm diameter) there was a persistent waist indicating a residual narrowing. Use of an extra-high pressure balloon, Conquest® (Medicon, Osaka, Japan) balloon of the same size, completely eliminated the waist. In in vitro experiments, the Mustang® partially tore the ePTFE, while a Conquest® of the same diameter completely opened the band. The mechanism of debanding was tearing of the ePTFE by the knot of the suture thread. Percutaneous pulmonary debanding to avoid unnecessary surgery is feasible in such a patient if the VSD becomes small. .

Long-term outcomes of gastric band removal without additional bariatric surgery.

OBJECTIVE: The outcomes of patients undergoing band removal alone without an additional bariatric procedure after laparoscopic gastric banding are not well reported. We seek to close this gap in the literature. SETTING: Cantonal Hospital & University Teaching Hospital, Switzerland METHODS: In this retrospective study, we investigated 21 patients who underwent band removal with a mean follow-up of 63 months. Weight regain, co-morbidities, and quality of life were assessed. RESULTS: The laparoscopic gastric bandings were implanted at a mean initial body mass index (BMI) of 44.6 kg/m2. The bands remained in situ for an average of 87.7 months (range: 14-185 mo). The reasons for band removal included band slippage in 9 cases (42.9%), band penetration in 6 cases (28.6%), leakage, port infection, and patient request in 2 cases (9.5% each). The average BMI at the time of band removal was 34.9 kg/m2. At 62.9 months after band removal, patients regained an average of 17.3 kg and attained a mean BMI of 41.0 kg/m2. Co-morbidities such as type 2 diabetes, arterial hypertension, obstructive sleep apnea, and psychiatric disorders worsened during the follow-up period. Thirteen of 21 patients rated their quality of life as bad, 5 as mediocre, and only 3 as good. Only 2 patients said they would undergo a gastric banding procedure again. The patients achieved an average of-.6 points on the Moorehead-Ardelt quality of life score, which indicates a fair quality of life. CONCLUSION: This study finds that reversal of gastric banding procedures with removal of the banding system alone leads to weight regain, deterioration of physical and psychiatric co-morbidities, and low quality of life scores.

Myocardial mechanics in a rat model with banding and debanding of the ascending aorta.

BACKGROUND: Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. METHODS: Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 ± 0.8 vs. 33.2 ± 2.0 vs. 26.6 ± 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 ± 0.20% vs. 5.26 ± 3.12% vs. 4.03 ± 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Myocardial Mechanics in a Rat Model with Banding and Debanding of the Ascending Aorta

BACKGROUND: Aortic banding and debanding models have provided useful information on the development and regression of left ventricular hypertrophy (LVH). In this animal study, we aimed to evaluate left ventricular (LV) deformation related to the development and regression of LVH. METHODS: Minimally invasive ascending aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats underwent a sham operation. Thirty-five days later, the band was removed. Echocardiographic and histopathologic analysis was assessed at pre-banding, 35 days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta created an expected increase in the aortic velocity and gradient, which normalized with the debanding procedure. Pressure overload resulted in a robust hypertrophic response as assessed by gross and microscopic histology, transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 +/- 0.8 vs. 33.2 +/- 2.0 vs. 26.6 +/- 2.8, p < 0.001]. The circumferential (CS) and radial strains were not different between the groups. However, there were significant differences in the degree of fibrosis according to the banding status (fibrosis; 0.10 +/- 0.20% vs. 5.26 +/- 3.12% vs. 4.03 +/- 3.93%, p = 0.003), and global CS showed a significant correlation with the degree of myocardial fibrosis in this animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating a severe LV pressure overload state, a significant increase in the LV mass index did not result in a significant reduction in the LV mechanical parameters. The degree of LV fibrosis, which developed with pressure overload, was significantly related to the magnitude of left ventricular mechanics.

Pulmonary artery debanding.

Pulmonary artery banding is a simple palliative surgical procedure for congenital heart defects with left-to-right shunt or complete mixing and pulmonary over-circulation. Even though indication for pulmonary artery banding has been sensibly reduced, since early reparative surgery has been proved superior to palliation and a staged approach, an increasing support for pulmonary banding has been raised in the last two decades by new indications such as left ventricular retraining, in the late arterial switch operation for complete transposition of the great arteries or before the double-switch operation in congenitally corrected transposition. Along with the increasing interest raised by the new indications and the consequently more diffuse use of banding, debanding has become an important surgical issue. Debanding is usually performed several months after palliation along with the repair of the cardiac malformations; otherwise, it can be done progressively or partially to further delay surgery and let the patient grow. Occasionally, after pulmonary artery banding, a spontaneous resolution of the underlying cardiac malformation can occur; however, a debanding procedure is in any case necessary.

Feasibility of VSD Closure and Debanding Without Pulmonary Artery Patch Repair in VSD Patients After PA Banding.

From 2004 to 2008, 64 infants with large ventricular septal defects were managed using a two-stage surgical approach. In the first stage, banding of the main pulmonary trunk was performed. The defect was then repaired months later. Debanding of pulmonary artery was accomplished without the need for pulmonary artery reconstruction.