Pulmonary artery pulsatility index predicts prolonged inotrope/pulmonary vasodilator use after implantation of continuous flow left ventricular assist device

Objective: Predictors of right ventricle (RV) dysfunction after continuous‐flow left ventricular assist device (CF‐LVAD) implantation in children are not well described. We explored the association of preimplantation Pulmonary Artery Pulsatility index (PAPi) and other hemodynamic parameters as predictors of prolonged postoperative inotropes/pulmonary vasodilator use after CF‐LVAD implantation.
Design: Retrospective chart review.
Setting: Single tertiary care pediatric referral center.
Patients: Patients who underwent CF‐LVAD implantation from January 2012 to October 2017.
Interventions: Preimplantation invasive hemodynamic parameters were analyzed to evaluate the association with post‐CF‐LVAD need for prolonged (>72 hours) use of inotropes/pulmonary vasodilators.
Measurements and main results: Preimplantation cardiac catheterization data was available for 12 of 44 patients who underwent CF‐LVAD implant during the study period. Median (IQR) age and BSA of the cohort were 15.3 years (10.2, 18) and 1.74 m2 (0.98, 2.03). Group 1 (n = 6) included patients with need for prolonged inotropes/pulmonary vasodilator use after CF‐LVAD implantation and Group 2 (n = 6) included those without. Baseline demographic parameters, cardiopulmonary bypass time, and markers of RV afterload (pulmonary vascular resistance, PA compliance and elastance) were similar among the two groups. PAPi was significantly lower in group 1 compared to group 2 (0.96 vs 3.6, respectively; P = .004). Post‐LVAD stay in the intensive care unit was longer for patients in group 1 (46 vs 23 days, P = .52). Brain natriuretic peptide was significantly higher at 3 months after implantation in group 1; P = .01.
Conclusions: The need for inotropes/pulmonary vasodilators in the postoperative period can be predicted by the preimplantation intrinsic RV contractile reserve as assessed by PAPi rather than the markers of RV afterload. Further investigation and correlation with clinical outcomes is needed.     

Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development

Plasmodium falciparum-derived cysteine protease falcipain-2 cleaves host erythrocyte hemoglobin at acidic pH and specific components of the membrane skeleton at neutral pH. Analysis of stage-specific expression of these 2 proteolytic activities of falcipain-2 shows that hemoglobin-hydrolyzing activity is maximum in early trophozoites and declines rapidly at late stages, whereas the membrane skeletal protein hydrolyzing activity is markedly increased at the late trophozoite and schizont stages. Among the erythrocyte membrane skeletal proteins, ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini. To identify the precise peptide sequence at the hydrolysis site of protein 4.1, we used a recombinant construct of protein 4.1 as substrate followed by MALDI-MS analysis of the cleaved product. We show that falcipain-2-mediated cleavage of protein 4.1 occurs immediately after lysine 437, which lies within a region of the spectrin-actin-binding domain critical for erythrocyte membrane stability. A 16-mer peptide containing the cleavage site completely inhibited the enzyme activity and blocked falcipain-2-induced fragmentation of erythrocyte ghosts. Based on these results, we propose that falcipain-2 cleaves hemoglobin in the acidic food vacuole at the early trophozoite stage, whereas it cleaves specific components of the red cell skeleton at the late trophozoite and schizont stages. It is the proteolysis of skeletal proteins that causes membrane instability, which, in turn, facilitates parasite release in vivo.     

Guidewire pacing during transcatheter aortic valve implantation in a patient with complex congenital heart disease

We present a case of temporary guidewire pacing in a patient with Fontan anatomy during transcatheter aortic valve implantation. Temporary pacing was successfully achieved utilizing this method without complications. There is an increasing population of patients with complex congenital heart disease and expanding variety of transcatheter interventions. Due to limitations in vascular access and surgical anatomies, guidewire pacing may have a wide array of potential applications in pediatrics and the congenital heart disease population.     

Risk of cardiac arrhythmias and conduction abnormalities in patients with acute myocardial infarction receiving packed red blood cell transfusions

Purpose

Although transfusion has been linked to the development of atrial fibrillation (AF) in cardiac surgical patients, this association has not been investigated in patients with acute myocardial infarction (AMI). Evidence supports an inflammatory mechanism in the development of AF, and red cell transfusions also elicit an inflammatory response. We therefore sought to evaluate whether packed red blood cell transfusion increases the risk of AF, ventricular tachycardia (VT), and other arrhythmias and conduction abnormalities in patients with AMI.

Materials and Methods

This is a retrospective study on patients with AMI and no prior history of AF, admitted to a critical care area and entered in Project Impact database from 08/2003-12/2007. Primary outcome measures were new-onset cardiac arrhythmias or conduction disturbances.

Results

Transfused patients had significantly higher incidences of AF (4.7% vs 1.3%, P = .008), cardiac arrest (9.5% vs 1.7%, P < .001) and heart block (3.4% vs 0.1%, P < .001), and a trend toward a higher incidence of VT (3.4% vs 1.3%, P = .058). Multivariate regression analysis confirmed transfusion as an independent risk factor for “non-lethal” cardiac events (AF/heart block; odds ratio [OR], 4.7 [1.9-11.9]; P = .001), “lethal” events (VT/cardiac arrest; OR, 2.4 [1.1-5]; P = .016), and all cardiac events (OR, 2.8 [1.5-65.1]; P = .001). Transfused patients had significantly longer length of stay (P < .0001) and significantly higher mortality rates than nontransfused patients (OR, 3 [1.7-5.5]; P < .001).

Conclusions

Packed red blood cell transfusion is independently associated with an increased risk of new-onset cardiac arrhythmias and conduction abnormalities in the setting of AMI, even after controlling for traditional risk factors.     

Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1

Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P(2)). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.     

Stapled Hemorrhoidopexy: The Aga Khan University Hospital Experience

Background/Aim:

Stapled hemorrhoidopexy for prolapsing hemorrhoids is conceptually different from excision hemorrhoidectomy. It does not accompany the pain that usually occurs after resection of the sensitive anoderm. This study was carried out to evaluate the clinical outcome of stapled hemorrhoidopexy at The Aga Khan University Hospital.

Materials and Methods:

A sample of 140 patients with symptomatic second-, third-, and fourth-degree hemorrhoids and circumferential mucosal prolapse underwent stapled hemorrhoidopexy from July 2002 to July 2007. They were evaluated for postoperative morbidity, analgesic requirement, and recurrence.

Results:

Seventy-eight percent were males and the mean age was 45 (range 16-90) years. The mean operative time was 35 (15-78) min. The mean parenteral analgesic doses during the first 24 h were 2.1. All patients received oral analgesics alone after 24 h. No significant postoperative morbidity was observed. The mean in-patient hospital stay was 1.3 (0-5) days. Patients were followed-up for 24 (range, 2-48) months. Minor local recurrence of hemorrhoids was seen in four patients and was managed by band ligation.

Conclusion:

Stapled hemorrhoidopexy procedure was found safe, well tolerated by patients with minimal parenteral analgesic use and early discharge from the hospital.     

Safety and Feasibility of Melody Transcatheter Pulmonary Valve Replacement in the Native Right Ventricular Outflow Tract: A Multicenter Pediatric Heart Network Scholar Study

Objectives

This study sought to determine the safety and feasibility of transcatheter pulmonary valve replacement (TPVR) using the Melody valve in native (nonconduit) right ventricular outflow tracts (nRVOT), and to identify factors associated with successful TPVR.