Aortic aneurysms and dissections: Unmet needs from physicians and engineers perspectives.

The treatment of aortic disease is complex, requiring cardiothoracic and vascular surgeons to make pre-, post- and intraoperative decisions directly influencing patient survival and well-being. Despite tremendous advancement in vascular surgery and endovascular techniques in the last two decades, along with the abundance of research in the field, many unmet needs and unanswered questions remain. Tight collaboration between engineers and physicians is a keystone in translating new tools, techniques, and devices into practice. Here, we have gathered our perspective, as physicians and engineers, in several pressing issues associated with the diagnosis and treatment of aortic aneurysms and dissection, referring to the current knowledge and practice, signifying unmet needs as well as future directions.

Pre- and Post-Transcatheter Aortic Valve Replacement Serum Brain Natriuretic Peptide Levels and All-Cause Mortality.

BACKGROUND: Risk stratification in patients post-transcatheter aortic valve replacement (TAVR) is limited to and is based on clinical judgment and surgical scoring systems. Serum natriuretic peptides are used for general risk stratification in patients with aortic stenosis, reflecting the increase in their afterload and thereby stressing the need for valve intervention. The objective of this study was to determine the predictive value of pre- and post-procedural serum brain natriuretic peptide (BNP) on 1-year all-cause mortality in patients who underwent TAVR. METHODS: In this population-based study, we included 148 TAVR patients treated at the Poriya Medical Center between June 1, 2015, and May 31, 2018. Routine blood samples for serum BNP levels (pg/mL) were taken just before the TAVR and 24 h post-TAVR. Our primary clinical outcome was defined as 1-year all-cause mortality. We used backward regression models and included all variables that had a p value <0.1 in the univariable analysis. A receiver-operating characteristic curve was calculated for the prediction of all-cause mortality by serum BNP levels using the median as the cut-off point. RESULTS: In this study cohort, BNP levels 24 h post-TAVR higher than the cohort median versus lower than the cohort median (387.5 pg/mL; IQR 195-817.6) were the strongest predictor of 1-year mortality (hazard ratio 9; 95% CI 2.72-30.16; p < 0.001). The statistically significant relationship was seen in the unadjusted regression model as well as after the adjustment for clinical variables. CONCLUSIONS: Serum BNP levels 24 h post-procedure were found to be a meaningful marker in predicting 1-year all-cause mortality in patients after TAVR procedure.

Developments in parallel grafts for aortic arch lesions.

Due to the shortage of commercially available off the shelf aortic arch grafts since the last years parallel grafts or chimney grafts have played an increasing role in the treatment of patients with aortic arch lesions. Although there are still issues with type endoleaks and gutters between the chimney graft and the aortic stent-graft remaining. We report our results with the Medtronic thoracic graft in combination with long self-expanding parallel grafts, to ensure an overlapping zone of more than 7 cm between the different grafts. Alternatively, sandwich configurations are used where a direct contact between the parallel graft and the aortic wall is avoided. We have placed a total of 65 parallel grafts into supra-aortic branches. In 21 cases chimney grafts were placed into the carotid artery, in most cases into the left common carotid artery. In 36 cases chimney grafts were placed into left subclavian artery. A maximum number of 4 parallel grafts were placed for total endovascular debranching. In addition, in 8 patients a parallel graft had to be placed into the innominate artery. There was a patency of 69% for all subclavian artery chimney grafts versus 73% for carotid artery parallel grafts. Of note is a stroke rate of 5.2% in all these cases. Only 2 of the patients with an occluded left subclavian artery chimney graft required a bypass procedure for arm claudication or ischemia. We had a primary type I endoleak rate of 28%. In almost 25% secondary interventions were required mainly to treat type I leaks, in those cases where the leak did not resolve spontaneously. The overall mortality rate was 3.5%. The results of parallel graft in the aortic arch are promising, but of major concern is still the high rate of type I endoleaks as well as the neurological complication rate, most probably due to catheter manipulation in patients with severe atherosclerotic arch lesions.

Human carotid plaque phosphatidylcholine specifically interacts with paraoxonase 1, increases its activity, and enhances its uptake by macrophage at the expense of its binding to HDL.

Human carotid atherosclerotic plaque is in direct contact with circulatory blood components. Thus, plaque and blood components may affect each other. The current study presents the effects of plaque chloroform:methanol (C:M) extract on the HDL-associated enzyme paraoxnase 1 (PON1). This study is part of our investigation on the mutual effects of the interactions between atherosclerotic lesions and blood components. Recombinant PON1 (rePON1) was incubated with the human carotid plaques C:M extract and PON1 activities were analyzed. Lactonase and paraoxonase activities were elevated due to C:M treatment, by 140 and by 69%, respectively. Analytical chemistry analyses revealed specific phosphatidylcholines (PCs) as the plaque active components. Tryptophan fluorescence quenching assay, together with molecular docking, shows that PON1 activity is enhanced in correlation with the level of PC affinity to PON1. Molecular docking revealed that PCs interact specifically with H2-PON1 α-helix, which together with H1 enzyme α-helix links the protein to the HDL surface. These findings are supported by additional results from the PON1 ∆20 mutant that lack its H1-α-helix. Incubation of this mutant with the plaque C:M extract increased PON1 activity by only 20%, much less than the wild-type PON1 that elevated PON1 activity at the same concentration by as much as 95%. Furthermore, as much as the affinity of the enzyme to the PC was augmented, the ability of PON1 to bind to the HDL particle decreased. Finally, PON1 interaction with PC enhance its uptake into the macrophage cytoplasm. In conclusions, Specific lesion phosphatidylcholines (PCs) present in the human carotid plaque significantly enhance PON1 catalytic activities due to their interaction with the enzyme. Such a lesion׳s PC-PON1 interaction, in turn, competes with HDL PCs and enhances PON1 uptake by macrophage at the expense of PON1 binding to the HDL.

Increased Levels of Human Carotid Lesion Linoleic Acid Hydroperoxide in Symptomatic and Asymptomatic Patients Is Inversely Correlated with Serum HDL and Paraoxonase 1 Activity.

Human carotid plaque components interact directly with circulating blood elements and thus they might affect each other. We determined plaque paraoxonase1 (PON1) hydrolytic-catalytic activity and compared plaque and blood levels of lipids, HDL, PON1, and HbA1c, as well as plaque-oxidized lipids in symptomatic and asymptomatic patients. Human carotid plaques were obtained from symptomatic and asymptomatic patients undergoing routine endarterectomy, and the lesions were ground and extracted for PON activity and lipid content determinations. Plaque PONs preserved paraoxonase, arylesterase, and lactonase activities. The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity. Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels. Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels. Thus LA-13OOH, a major atherogenic plaque element, showed significant negative correlations with serum PON1 activity and HDL levels, and a positive correlation with the prodiabetic atherogenic HbA1c. Plaque PON1 retains its activity and may decrease plaque atherogenicity by reducing specific oxidized lipids (e.g., LA-13OOH). The inverse correlation between plaque LA-13OOH level and serum HDL level and PON1 activity suggests a role for serum HDL and PON1 in LA-13OOH accumulation.

Modified alternating current defibrillation: a new defibrillation technique.

AIMS: Defibrillation is the only clinically effective treatment for ventricular fibrillation (VF). Early defibrillation improves the outcome and increases the chance of survival with full recovery. Immediate availability of a home-based defibrillator using mains-derived alternating current (AC) current will drastically improve the outcome. The aim was to develop a defibrillator based on the modulated AC, resembling biphasic configuration, and compare its efficacy, in a pig model, with a standard direct current (DC) defibrillator. METHODS AND RESULTS: A computer controlled, modulated AC defibrillation system was developed using a high-voltage switch and a high-voltage transformer. The efficacy and safety was evaluated in five pigs (30-40 kg), under general anaesthesia with ketamine and isoflouran. A single quadripolar-pacing catheter was inserted percutaneously. Ventricular fibrillation was induced with rapid ventricular burst pacing, and stable VF was defibrillated after 15 s. Defibrillation threshold (DFT) was determined in each animal with AC and standard DC shock using the step-down protocol. A biphasic-like shock was used with a short isoelectric stage between the phases. The DFT with AC was 70.83 +/- 24.81 J and with DC was 65.83 +/- 12.41 J (P = 0.49). No macroscopic damage was observed after AC or DC defibrillation. CONCLUSION: Modulated AC defibrillation is safe and effective as the commercially available DC defibrillation. The defibrillator is built from an inexpensive high-voltage transformer, without the need for capacitor, batteries, or routine maintenance, delivers repeated shock without any delay, and provides pacing as well. It may be an ideal platform for automatic home defibrillator.