TMEM16A Regulates Pulmonary Arterial Smooth Muscle Cells Proliferation via p38MAPK/ERK Pathway in High Pulmonary Blood Flow-Induced Pulmonary Arterial Hypertension

<b><i>Objective:</i></b> Pulmonary arterial hypertension (PAH) is a complex disease of the small pulmonary arteries that is mainly characterized by vascular remodeling. It has been demonstrated that excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a pivotal role in vascular remodeling during PAH. The present study was undertaken to explore the role of TMEM16A in regulating PASMCs proliferation in high pulmonary blood flow-induced PAH. <b><i>Methods:</i></b> Aortocaval shunt surgery was undertaken to establish an animal model. Pulmonary artery pressure and pulmonary vascular structure remodeling (PVSR) were tested. Immunohistochemical staining and Western blot were performed to investigate the expression of TMEM16A. The proliferation of PASMCs was tested by the MTT assay. After treating PASMCs with TMEM16A-siRNA, the expression of proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), and phosphorylated extracellular signal-regulated kinase (p-ERK) signaling in PASMCs were tested. <b><i>Results:</i></b> PAH and PVSR developed 11 weeks postoperation. Elevated expression of TMEM16A accompanied by high expression of PCNA in pulmonary arteries of the shunt group was observed. The increased proliferation of PASMCs and increased expression of TMEM16A and PCNA, along with activated p-p38MAPK and p-ERK signaling in PASMCs of the shunt group, were all attenuated by siRNA-specific TMEM16A knockdown. <b><i>Conclusion:</i></b> TMEM16A regulates PASMCs proliferation in high pulmonary blood flow-induced PAH, and the p38MAPK/ERK signaling pathway is probably involved.

Right ventricle function longitudinal evaluation after norwood procedure: comparison between right ventricle-pulmonary artery shunt and blalock-taussing shunt

Background Norwood procedure represents the first of three surgical steps toward Hypoplastic left heart syndrome (HLHS) complete palliation. Two are the main surgical techniques allowing the reconstruction of Norwood circulation: the right ventricle-pulmonary artery shunt (RVPAS) and the modified Blalock-Taussing shunt (mBTS). However, still little is known about the impact on right ventricle (RV) function of the required ventriculotomy for the RVPAS. Purpose The aim of the study was to investigate the changes in RV function in HLHS patients after RVPAS vs mBTS. Methods The cohort included 27 consecutive HLHS patients (10 in the modified Blalock-Taussig shunt group and 17 in the RVPAS group) who successfully underwent Norwood procedure in a single tertiary paediatric cardiology centre. Longitudinal strain (LS) and strain rate (LSR), tricuspid annulus peak systolic excursion (TAPSE) and fractional area change (FAC) were evaluated in all patients before Norwood and in three different breakpoints in the steady state after Norwood procedure (30 days after Norwood, 90 days after Norwood, 140 days after Norwood). Results Ventricular loading conditions (diuretic treatment, blood pressure and tricuspid regurgitation) were similar in both groups. No significant differences were found at different time points between RVPAS and mBTS group in terms of LS, LSR, TAPSE and FAC. However, when we compared RV function before and after Norwood procedure, 90 days after the procedure, patients who did not undergo RV ventriculotomy (mBTS group) showed significant improvement in LS compared to pre-surgical assessment (mBTS: +27.35±43.47% vs RVPAS: −8,20±25.25%, p=0,03). This finding was consistent but no longer statistically significant at 140 days after Norwood (mBTS: +13.81±21.99% vs RVPAS: −4.90±27.97%, p=0,12). Conclusion After Norwood procedure mBTS patients showed a significant increase in LS when compared with patients who underwent RVPAS. This finding was consistent but no longer significant at 140 days after Norwood probably because the number of patients was too small to reach a significant level. These data support the use of LS in HLHS patient's evaluation and may be of value to find a patient-tailored timing for the second surgical stage. TAPSE, FAC, LS and LSR trends Funding Acknowledgement Type of funding source: None

Echocardiographic diagnosis of right-to-left shunt using transoesophageal and transthoracic echocardiography

BackgroundThe diagnosis and quantification of right-to-left shunt (RLS) using transthoracic echocardiography (TTE) as well as transoesophageal echocardiography (TOE) have not been well established. We aimed to diagnose RLS by TOE using direct visualisation of the shunt and to compare the diagnosis with TTE diagnosis using conventional methods.Methods and resultsWe evaluated 141 patients with ischaemic stroke for RLS by both non-sedation TOE and TTE using saline contrast and Valsalva manoeuvre. The amount (graded as 0 to IV) and timing of RLS were demonstrated. All patients were classified into four groups by TOE based on direct visualisation of shunt through a patent foramen ovale (PFO) or either pulmonary vein: no shunt (group 1: n=11), PFO (group 2: n=47), pulmonary RLS (group 3: n=25) and indeterminate RLS (group 4: n=58). All cases in group 3 showed delayed shunt, and all cases in group 4 had small shunt. On TTE findings, all cases with early appearing large shunt (cardiac cycles ≤3 and shunt grade ≥III) were group 2. Six of the eight patients with delayed appearing large shunt on TTE were group 3. TTE diagnosis of PFO using criteria of cardiac beats ≤3 and grade ≥II had a sensitivity of 85% and a specificity of 98% compared with TOE diagnosis using shunt visualisation.ConclusionsCompared with TOE using shunt visualisation, TTE accurately diagnosed large PFO using criteria of cardiac cycles ≤3 and shunt grade ≥III. TTE possibly diagnosed pulmonary shunt using criteria of cardiac cycles >3 and shunt grade ≥III. Both modalities showed limitations in diagnosing small amount of RLS.

Atrial septal defect patients with greater shunts show susceptibility for ventricular arrhythmias

Objective: Ventricular arrhythmia episodes are not infrequent in patients with atrial septal defect (ASD). Disturbance in cardiac volume and pressures may lead to enlargement and fibrosis in heart. An interatrial volume displacement through septal defect, briefly interatrial shunt, is the major reason for this complication. Prolongation of the interval between the peak and end of the T wave (Tpeak to Tend, Tp-e) on the 12-lead electrocardiogram (ECG), is utilized as a marker of ventricular arrhythmogenesis during last years. The aim of this study was to assess if there is an impact of shunt ratio on ventricular repolarization in patients with ASD by using Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Methods: Patient records of Samsun Training and Research Hospital were retrospectively analyzed. Electrocardiograms of 133 patients, who were diagnosed as ASD between January 2016 and December 2019 were obtained and scanned. ECG intervals were measured. Shunt ratios, right ventricle diameters and volumes were also acquired. Patients were grouped into two by their calculated shunt ratio, ratio of ≥2.0 is accepted as a high shunt group and &lt;2.0 as a low shunt group. Results: Both groups’ baseline characteristics were similar. Right ventricular dimensions and systolic pulmonary artery pressure were higher in high shunt group. Furthermore, ASD patients with higher shunt ratio had significantly higher ECG measurements than controls, Tp-e: 103.0 (22.1) vs 76.2 (10.2); Tp-e/QT: 0.25 (0.03) vs 0.21 (0.02); Tp-e/QTc: 0.22 (0.03) vs, 0.17 (0.02); for all p&lt;0.001). Of all ECG parameters; Tp-e (r=0.631, p&lt;0.001), Tp-e/QT (r=0.531, p&lt;0.001) and Tp-e/QTc (r=0.614, p&lt;0.001) had moderate correlation with shunt ratio. Conclusion: T wave peak-to-end interval is a measure of transmural dispersion of repolarization and accepted as a surrogate for increased ventricular arrhythmogenesis risk. Our findings show that ASD patients whose shunt ratio are ≥2.0 show increased risk for arrhythmias. Key words: atrial septal defect, electrocardiogram, ventricular arrhythmia, risk, ventricular repolarization

Benefit of selective shunt use during carotid endarterectomy under regional anesthesia

Objectives Carotid cross-clamping during endarterectomy exposes the patient to intraoperative neurological deficits due to embolism or cerebral hypoperfusion. To prevent further cerebrovascular incidents, resorting to shunt is frequently recommended. However, since this method is also considered a stroke risk factor, the use is still controversial. This study aims to shed some light on the best approach regarding the use of shunt in symptomatic cerebral malperfusion after carotid artery cross-clamping. Methods From January 2012 to January 2018, 79 patients from a tertiary referral hospital who underwent carotid endarterectomy with regional anesthesia for carotid artery stenosis and manifested post-clamping neurologic deficits were prospectively gathered. Shunt use was left to the decision of the surgeon and performed in 31.6% (25) of the patients. Demographics, comorbidities, imaging tests, and clinical/intraoperative features were evaluated. For data assessment, univariate analysis was performed. Results Regarding 30-day stroke, 30-day postoperative complications (stroke, surgical hematoma, hyperperfusion syndrome), and cranial nerve injury, no significant differences were found ( P = 0.301, P = 0.460, and P = 0.301, respectively) between resource to shunt and non-shunt. Clamping and surgery times were significantly higher in the shunt group ( P < 0.001 and P = 0.0001, respectively). Conclusions Selective-shunting did not demonstrate superiority for patients who developed focal deficits regarding stroke or other postoperative complications. However, due to the limitations of this study, the benefit of shunting cannot be excluded. Further randomized trials are recommended for precise results on this matter with current sparse clinical evidence.

Risk factors associated with conversion of an Ommaya reservoir to a permanent cerebrospinal fluid shunt in preterm posthemorrhagic hydrocephalus

OBJECTIVEA considerable percentage of preterm infants with posthemorrhagic hydrocephalus initially managed with an Ommaya reservoir require a permanent CSF shunt. The objective of the study was to analyze possible risk factors associated with the need for converting an Ommaya reservoir to a permanent shunt.METHODSThe authors retrospectively reviewed the clinical records of premature infants weighing 1500 g or less with posthemorrhagic hydrocephalus (Papile grades III and IV) managed with an Ommaya reservoir at their institution between 2002 and 2017.RESULTSForty-six patients received an Ommaya reservoir. Five patients (10.9%) were excluded due to intraventricular infection during management with an Ommaya reservoir. Average gestational age and weight for the remaining 41 patients was 27 ± 1.8 weeks and 987 ± 209 grams, respectively. Thirty patients required a permanent shunt and 11 patients did not require a permanent shunt. The conversion rate from an Ommaya reservoir to a permanent shunt was 76.1%. Symptomatic persistent ductus arteriosus (PDA) was more frequent in the nonpermanent shunt group than in the shunt group (88.9% vs 50%, p = 0.04). The need for extraction of more than 10 ml/kg per day of CSF through the Ommaya reservoir was lower in the nonpermanent shunt group than in the shunt group (9.1% vs 51.7%, p = 0.015). CSF lactate was lower in the nonpermanent group than in the shunt group (mean 2.48 mg/dl vs 3.19 mg/dl; p = 0.004). A cutoff value of ≥ 2.8 mg/dl CSF lactate predicted the need for a permanent shunt with sensitivity and specificity of 82.4% and 80%, respectively. There were no significant differences in gestational age, sex, weight, Papile grade, ventricular index, or other biochemical markers. After the multivariate analysis, only CSF lactate ≥ 2.8 mg/dl was associated with a higher conversion rate to a permanent shunt.CONCLUSIONSThis study showed that a high level of CSF lactate, absence of symptomatic PDA, and a higher CSF extraction requirement were associated with a higher likelihood of implanting a permanent CSF shunt. The authors believe these findings should be considered in future studies.

Lumboperitoneal Shunt: A New Modified Surgical Technique and a Comparison of the Complications with Ventriculoperitoneal Shunt in a Single Center

Background and objectives: Hydrocephalus remains a disease requiring surgical treatment even in the modern era. Ventriculoperitoneal (VP) shunt placement is the most common treatment, whereas lumboperitoneal (LP) shunts are less commonly used due to initial reports of very high rates of complications. In the present study, we retrospectively reviewed our experience of the new two-stage procedure with LP shunt implantation to assess the complications and the results of this procedure versus VP shunt insertion. Materials and Methods: All patients from a single center who had received LP shunts using a Medtronic Strata device or VP shunts in the past six-year interval were retrospectively reviewed. The LP shunt insertion was a new two-stage procedure. We compared the three major complications and shunt revisions between the two groups, including shunt malfunction, infection, and subdural hematoma. Results: After matching the age and sex of both groups, we included 96 surgery numbers of LP shunts and 192 surgery numbers of VP shunts for comparison. In the LP shunt group, one patient (1.0%) underwent revision of the shunt due to shunt infection. In the VP shunt group, 26 surgeries (13.5%) needed revision, and 11 surgeries (5.7%) had shunt infection. Shunt malfunction occurred in 14 patients (7.3%) and all needed revisions. The revision rate showed statistically significant differences between the LP and VP shunt groups (p < 0.001). Conclusions: The recent improvements in the quality of the LP shunt device and the proficiency of the procedure has made the LP shunt a safer procedure than the VP shunt. The programmable valve can avoid overdrainage complications and reduce the revision rate. With our procedural steps, the LP shunt can be used to decrease the complications and revision rates.

Single-Stage Complete Repair versus Multistage Repair of Tetralogy of Fallot with Borderline Pulmonary Arteries

Background: Tetralogy of Fallot is the most common cyanotic congenital heart defect. Borderline pulmonary anatomy has been associated with a higher risk of mortality and morbidity. Strategies to manage this condition—namely, single- or multistage repair—have long been debated. Objective: The overall outcomes of patients with tetralogy of Fallot with borderline pulmonary arteries (McGoon ratio 1.3 to 1.7) with regard to the need for a single-stage or multistage repair and the outcome of each surgical management were evaluated. Patients and methods: A retrospective, nonrandomized comparative study designed to evaluate patient outcomes comprised 60 patients with tetralogy of Fallot with borderline pulmonary arteries who underwent surgery at the Cardiothoracic Surgery Academy, Ain Shams University, Cairo, Egypt, between January 2016 and December 2017. After gaining approval from the affiliated ethical and research committee, and informed consent of the guardians, the patients were assigned into one of two groups. Shunt group included 30 patients managed surgically by a modified Blalock-Taussig (MBT) shunt as a part of a multistage repair, and repair group included 30 patients managed surgically by single-stage complete repair. The medical records of the patients were reviewed, and data relating to age, sex, weight, and preoperative oxygen saturation were collected. All patients underwent preoperative echocardiography and multislice computed tomography (CT) with angiography. The follow-up was performed by echocardiography at discharge and at one month and six months after surgery. Multislice CT with angiography was performed in patients who received a shunt once the echocardiography showed acceptable pulmonary arteries. Results: The patients’ age ranged from 5 to 50 months with a mean age of 18.63 ± 9.15 (19.84 ± 12.34 for the shunt group and 17.43 ± 8.54 for the repair group). The weight ranged from 5 kg to 18 kg with a mean of 9.6 ± 2.53 (8.82 ± 2.79 for the shunt group and 10.41 ± 2.63 for the repair group). The mean preoperative O2 saturation was 68.95% ± 7.8% for the shunt group and 87.93% ± 6.18% for the repair group. The median McGoon ratio was 1.4 for the shunt group and 1.6 for the repair group, the difference of which was highly significant (P < .0001). The mortality rate in our study was 10% (10% for the shunt group and 10% for the repair group). The morbidity incidence rate was 26.6% for the shunt and repair groups. The ICU stay ranged from 2 to 31 days, with a median of three days for the shunt group (mean 3.61 ± 1.91) and four days for the repair group (mean 6.07 ± 6.63 days). The calculated P value showed a significant difference between the two groups concerning ICU stay. The postoperative SO2 significantly increased to a mean of 85.58 ± 7.05 in the shunt group and 98.14 ± 3.36 in the repair group (P < .0001). Conclusion: There was no statistically significant difference between multistage repair and single-stage complete repair regarding morbidity and mortality. Regarding ICU stay, patients in the single-stage had a better outcome. A McGoon ratio of 1.5 can be used as a guideline in the decision-making process.

Cryopreserved Saphenous Vein Compared With PTFE Graft for Use as Modified Blalock-Taussig or Central Shunt in Cyanotic Congenital Heart Disease

Many infants with congenital heart disease undergo palliative shunt procedures. In our center, cryopreserved saphenous vein and polytetrafluoroethylene (PTFE) are used as grafts to construct these shunts. In this retrospective review, we compare morbidity, mortality, and freedom from reoperation associated with the use of these graft materials. We conducted a retrospective study of 136 consecutive patients who were palliated with shunts between 2006 and 2015. A total of 136 patients were identified, 9 had incomplete data; thus, 127 patients were included: 69 saphenous and 58 PTFE. The cohorts were matched with respect to birth weight, gestational age, age and weight at time of surgery, and underlying cardiac condition. There were 15 (12%) deaths in the study cohort with no intraoperative mortality. Thrombosis was seen in 5.2% (2/38) of the saphenous modified Blalock-Taussig shunt (mBTS) group and 20.6% (14/68) of those with PTFE mBTS. There was no thrombosis in the central shunt group. Freedom from reoperation was 83% in the saphenous vein group and 81% in the PTFE group. There was no difference in overall morbidity or mortality, although thrombosis was significantly less in the saphenous vein group. Cryopreserved saphenous vein is a safe alternative, either as a mBTS or as a central shunt.

The Conundrum of Ventricular Dilatations Following Decompressive Craniectomy: Is Ventriculoperitoneal Shunt, The Only Panacea?

ABSTRACTIntroduction:Ventriculomegaly and hydrocephalus (HCP) are sometimes a bewildering sequela of decompressive craniectomy (DC). The distinguishing criteria between both are less well defined. Majority of the studies quoted in the literature have defined HCP radiologically, rather than considering the clinical status of the patient. Accordingly, these patients have been treated with permanent cerebrospinal fluid (CSF) diversion procedures. We hypothesize that asymptomatic ventriculomegaly following DC should undergo aspiration with cranioplasty and be followed up regularly. Materials and Methods: All patients with post-DC who were scheduled for cranioplasty and satisfied the radiological criteria for HCP were included. These patients were categorized into two groups. Group 1 included ventriculomegaly with clinical signs attributable to HCP and Group 2 constituted ventriculomegaly but no clinical signs attributable to HCP. All patients in Group 1 underwent ventriculoperitoneal shunt followed by cranioplasty, whereas all patients in Group 2 underwent cranioplasty along with simultaneous ventriculostomy and temporary aspiration of the lateral ventricle. All patients were regularly followed as the outpatient basis. Results: There were 21 patients who developed ventriculomegaly following DC. There were 10 patients in Group 1 and 11 patients in Group 2. The average duration of follow-up was from 6 months to 2 years. Two patients in the shunt group - (group 1) had over drainage and required revision. One patient in aspiration group - (group 2) required permanent CSF diversion. Conclusion: Cranioplasty with aspiration is a viable option in selected group of patients in whom there is ventriculomegaly but no signs or symptoms attributable to HCP.