In-hospital mortality of patients with acute coronary syndrome (ACS) after implementation of national health insurance (NHI) in Indonesia.

BACKGROUND: The National Health Insurance (NHI) was implemented in Indonesia in 2014, and cardiovascular diseases are one of the diseases that have overburdened the healthcare system. However, data concerning the relationship between NHI and cardiovascular healthcare in Indonesia are scarce. We aimed to describe changes in cardiovascular healthcare after the implementation of the NHI while determining whether the implementation of the NHI is related to the in-hospital mortality of patients with acute coronary syndrome (ACS). METHODS: This is a retrospective comparative study of two cohorts in which we compared the data of 364 patients with ACS from 2013 to 2014 (Cohort 1), before and early after NHI implementation, with those of 1142 patients with ACS from 2018 to 2020 (Cohort 2), four years after NHI initiation, at a tertiary cardiac center in Makassar, Indonesia. We analyzed the differences between both cohorts using chi-square test and Mann-Whitney U test. To determine the association between NHI and in-hospital mortality, we conducted multivariable logistic regression analysis. RESULTS: We observed an increase in NHI users (20.1% to 95.6%, p < 0.001) accompanied by a more than threefold increase in patients with ACS admitted to the hospital in Cohort 2 (from 364 to 1142, p < 0.001). More patients with ACS received invasive treatment in Cohort 2, with both thrombolysis and percutaneous coronary intervention (PCI) rates increasing more than twofold (9.2% to 19.2%; p < 0.001). There was a 50.8% decrease in overall in-hospital mortality between Cohort 1 and Cohort 2 (p < 0.001). CONCLUSIONS: This study indicated the potential beneficial effect of universal health coverage (UHC) in improving cardiovascular healthcare by providing more accessible treatment. It can provide evidence to urge the Indonesian government and other low- and middle-income nations dealing with cardiovascular health challenges to adopt and prioritize UHC.

A systematic review of the current status of interventions for type II endoleak after EVAR for abdominal aortic aneurysms.

OBJECTIVE: To study the mid- and long-term outcomes of type II endoleak treatment after EVAR and the technical aspects of different techniques to exclude endoleaks which different embolic agents. METHODS: A systematic review was performed using the approach recommended by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for meta-analyses of interventional studies. The comprehensive search was conducted using the following database: MEDLINE, EMBASE, and the Cochrane Library. Patient characteristic, intervention approaches, embolic agents, and results at mid and long term follow up were studied. RESULTS: A total of 6 studies corresponding to a total of 141 patients fulfilled the inclusion criteria with a mean age of 73-78.6 years and a mean duration of follow up varying from 25 to 42 months. There were different techniques for embolization used (translumbar, transarterial, and transcaval approach) with various types of embolic agents. In all studies, the indication for embolization of the type II endoleaks was sac enlargement of more than 5 mm. A wide range of technical success rate was reported regardless of the intervention strategy being used (17,6%-100%). The overall technical success rate of all studies was 62%. CONCLUSION: This systematic review shows that there is a wide variety of techniques to exclude a persistent type II endoleak. Different kinds of embolic agents have be used. Due to a lack of peer reviewed data on longterm follow-up, it was not possible to come to recommendations what treatment would be the best for a durable exclusion of a persistent type II endoleak after an initially successful EVAR. There remains an urgent need for proper executed studies, either randomized or with close observation in relation to longer follow-up.

Extracellular traps derived from macrophages, mast cells, eosinophils and neutrophils are generated in a time-dependent manner during atherothrombosis.

Extracellular traps generated by neutrophils contribute to thrombus progression in coronary atherosclerotic plaques. It is not known whether other inflammatory cell types in coronary atherosclerotic plaque or thrombus also release extracellular traps. We investigated their formation by macrophages, mast cells, and eosinophils in human coronary atherosclerosis, and in relation to the age of thrombus of myocardial infarction patients. Coronary arteries with thrombosed or intact plaques were retrieved from patients who died from myocardial infarction. In addition, thrombectomy specimens from patients with myocardial infarction were classified histologically as fresh, lytic or organised. Neutrophil and macrophage extracellular traps were identified using sequential triple immunostaining of CD68, myeloperoxidase, and citrullinated histone H3. Eosinophil and mast cell extracellular traps were visualised using double immunostaining for eosinophil major basic protein or tryptase, respectively, and citrullinated histone H3. Single- and double-stained immunopositive cells in the plaque, adjacent adventitia, and thrombus were counted. All types of leucocyte-derived extracellular traps were present in all thrombosed plaques, and in all types of the in vivo-derived thrombi, but only to a much lower extent in intact plaques. Neutrophil traps, followed by macrophage traps, were the most prominent types in the autopsy series of atherothrombotic plaques, including the adventitia adjacent to thrombosed plaques. In contrast, macrophage traps were more numerous than neutrophil traps in intact plaques (lipid cores) and organised thrombi. Mast cell and eosinophil extracellular traps were also present, but sparse in all instances. In conclusion, not only neutrophils but also macrophages, eosinophils, and mast cells are sources of etosis involved in evolving coronary thrombosis. Neutrophil traps dominate numerically in early thrombosis and macrophage traps in late (organising) thrombosis, implying that together they span all the stages of thrombus progression and maturation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Neutrophil Extracellular Traps Participate in All Different Types of Thrombotic and Haemorrhagic Complications of Coronary Atherosclerosis.

Acute coronary syndromes can be initiated by either atherosclerotic fibrous cap ruptures, superficial plaque erosions or intraplaque haemorrhages (IPHs). Since neutrophil extracellular traps (NETs) display pro-inflammatory and pro-thrombotic properties, we investigated the presence, extent and distribution of neutrophils and NETs in different types of plaque complications in relation to the age of overlying thrombus mass or haemorrhage. Sixty-four paraffin-embedded coronary plaque segments of 30 acute myocardial infarction patients were retrieved from the autopsy archives, which contained 44 complicated plaques (17 IPHs, 9 erosions and 18 ruptures) and 20 intact plaques. Complicated plaques were further categorized according to the histological age of thrombus or haemorrhage. Immunohistochemistry was performed to visualize neutrophils (anti-myeloperoxidase, anti-elastase and anti-CD177) and NETs (anti-citrullinated histone-3 and anti-peptidyl-arginine-deiminase-4). The results were scored semi-quantitatively. Neutrophils and NETs were abundantly present in all types of complicated, but not in intact, plaques (p < 0.05). They were found in thrombus, haemorrhages and at the thrombus-plaque interface, with no significant differences in extent between ruptures, erosions and IPHs. Interestingly, adjacent perivascular tissue of complicated, but not of intact plaques, also contained high numbers of neutrophils and NETs (p < 0.05). In thrombus and haemorrhage of different age, neutrophils and NETs were more frequently present in non-organized (fresh) thrombi and in on-going IPHs. In conclusion, netosis is a prominent pro-thrombotic participant in all distinct types of atherothrombosis, which may facilitate the progression of thrombotic or haemorrhagic complications and thus the onset of ensuing clinical coronary ischemic syndromes.

Pregnancy-related conditions and premature coronary heart disease in adult offspring.

OBJECTIVE: To investigate the association between complications during pregnancy and premature coronary heart disease in adult offspring. METHODS: We conducted a population-based case-control study of 153 Indonesian patients with a first acute coronary syndrome (ACS) (age ≤55 years) and 153 age-matched and sex-matched controls. Data on complications during pregnancy (high blood pressure, preterm delivery) and maternal infections in pregnancy were obtained, together with sociodemographic data, clinical profiles, laboratory measurements and adulthood cardiovascular disease (CVD) risk factors at hospital admission or enrolment. Conditional logistic regression was performed to assess the association between overall pregnancy complications, and specific groupings of complications and premature ACS. RESULTS: Pregnancy-related hypertension and infection were more common in mothers of cases than controls. Pregnancy complications were associated with premature offspring ACS (OR 2.9, 95% CI 1.4 to 6.0, p=0.004), and the association persisted in fully adjusted analyses (ORadjusted 4.5, 1.1 to 18.1, p=0.036). In subgroup analyses, pregnancy-related high blood pressure (ORadjusted 5.0, 1.0 to 24.7, p=0.050) and maternal infections (ORadjusted 5.2, 1.1 to 24.2, p=0.035) were associated with offspring ACS. CONCLUSIONS: Offspring of mothers with complications during pregnancy have an increased risk for premature ACS in adulthood, which may be of particular relevance in populations in transition, where the incidence of both pregnancy-related morbidity and CVD are high.

Infections in early life and premature acute coronary syndrome: A case-control study.

BACKGROUND: Infections in young children may affect the vasculature and initiate early atherosclerosis. Whether infections experienced in childhood play a part in adult clinical cardiovascular disease remains unclear. We investigated the association between infections in early life and the occurrence of premature coronary heart disease. METHODS: We conducted a population-based case-control study of 153 patients with a first acute coronary syndrome before the age of 56 years and 153 age- and sex-matched controls. Any history of severe infections in childhood and adolescence was obtained, together with clinical and laboratory measurements and other cardiovascular risk factors. We developed an infection score for the overall burden of early life infections. Conditional logistic regression was used to assess the associations. RESULTS: Infections experienced in early life increased the risk of acquiring acute coronary syndrome at a young age with an odds ratio (OR) of 2.67 (95% confidence interval (CI) 1.47-4.83, p = 0.001). After adjustments for traditional risk factors, lifestyle, dietary patterns, socio-economic status and parental history of cardiovascular events, these associations remained significant and changed only slightly. There was an indication for an interaction between infections in early life and current cardiovascular risk (Framingham Risk Score (FRS); p-interaction = 0.052). Within participants with a low FRS (<10%), the OR of early life infection for acute coronary syndrome was 1.49 (95% CI 0.72-3.08, p = 0.283); within participants with an intermediate FRS (10-20%), the OR was 4.35 (95% CI 1.60-11.84, p = 0.004); and within participants with a high FRS (>20%), the OR 10.00 (95% CI 1.21-82.51, p = 0.032). CONCLUSION: Infections in early life may partly explain premature coronary heart disease in adulthood and may potentiate traditional cardiovascular risk factor effects.

Laser-assisted vascular welding: optimization of acute and post-hydration welding strength.

BACKGROUND: Liquid solder laser-assisted vascular welding using biocompatible polymeric scaffolds (ssLAVW) is a novel technique for vascular anastomoses. Although ssLAVW has pronounced advantages over conventional suturing, drawbacks include low welding strength and extensive thermal damage. AIM: To determine optimal ssLAVW parameters for maximum welding strength and minimal thermal damage. METHODS: Substudy 1 compared breaking strength (BS) of aortic strips welded with electrospun poly(ε-caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) scaffold, 670-nm laser, 50-s single-spot continuous lasing (SSCL), and semi-solid solder (48% bovine serum albumin (BSA)/0.5% methylene blue (MB)/3% hydroxypropylmethylcellulose (HPMC)). Substudy 2 compared the semi-solid solder to 48% BSA/0.5% MB/0.38% genipin and 48% BSA/0.5% MB/3% HPMC/0.38% genipin solder. Substudy 3 compared SSCL to single-spot pulsed lasing (SSPL). RESULTS: PCL-ssLAVW yielded an acute BS of 248.0 ± 54.0 N/cm2 and remained stable up to 7d of hydration. PLGA-ssLAVW obtained higher acute BS (408.6 ± 78.8 N/cm2) but revealed structural defects and a BS of 109.4 ± 42.6 N/cm2 after 14 d of hydration. The addition of HPMC and genipin improved the 14-d BS of PLGA-sLAVW (223.9 ± 19.1 N/cm2). Thermal damage was reduced with SSPL compared with SSCL. CONCLUSIONS: PCL-ssLAVW yielded lower but more stable welds than PLGA-ssLAVW. The addition of HPMC and genipin to the solder increased the post-hydration BS of PLGA-ssLAVW. SSPL regimen reduced thermal damage. PLGA-ssLAVW using 48% BSA/0.5% MB/3% HPMC/0.38% genipin solder and SSPL constitutes the most optimal welding modality. RELEVANCE FOR PATIENTS: Surgical patients requiring vascular anastomoses may benefit from the advantages that ssLAVW potentially offers over conventional sutures (gold standard). These include no needle trauma and remnant suture materials in the patient, reduction of foreign body reaction, immediate liquid-tight sealing, and the possibility of a faster and easier procedure for minimally invasive and endoscopic anastomotic techniques.

Laser-assisted vessel welding: state of the art and future outlook.

Laser-assisted vascular welding (LAVW) is an experimental technique being developed as an alternative to suture anastomosis. In comparison to mechanical anastomosis, LAVW is less traumatic, non-immunogenic, provides immediate water tight sealant, and possibly a faster and easier procedure for minimally invasive surgery. This review focuses on technical advances to improve welding strength and to reduce thermal damage in LAVW. In terms of welding strength, LAVW has evolved from the photothermally-induced microvascular anastomosis, requiring stay sutures to support welding strength, to sutureless anastomoses of medium-sized vessels, withstanding physiological and supraphysiological pressure. Further improvements in anastomotic strength could be achieved by the use of chromophore-containing albumin solder and the employment of (biocompatible) polymeric scaffolds. The anastomotic strength and the stability of welds achieved with such a modality, referred to as scaffold- and solder-enhanced LAVW (ssLAVW), are dependent on the intermolecular bonding of solder molecules (cohesive bonding) and the bonding between solder and tissue collagen (adhesive bonding). Presently, the challenges of ssLAVW include (1) obtaining an optimal balance between cohesive and adhesive bonding and (2) minimizing thermal damage. The modulation of thermodynamics during welding, the application of semi-solid solder, and the use of a scaffold that supports both cohesive and adhesive strength are essential to improve welding strength and to limit thermal damage.

Ex vivo proof-of-concept of end-to-end scaffold-enhanced laser-assisted vascular anastomosis of porcine arteries.

OBJECTIVE: The low welding strength of laser-assisted vascular anastomosis (LAVA) has hampered the clinical application of LAVA as an alternative to suture anastomosis. To improve welding strength, LAVA in combination with solder and polymeric scaffolds (ssLAVA) has been optimized in vitro. Currently, ssLAVA requires proof-of-concept in a physiologically representative ex vivo model before advancing to in vivo studies. This study therefore investigated the feasibility of ex vivo ssLAVA in medium-sized porcine arteries. METHODS: Scaffolds composed of poly(ε-caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) were impregnated with semisolid solder and placed over coapted aortic segments. ssLAVA was performed with a 670-nm diode laser. In the first substudy, the optimum number of laser spots was determined by bursting pressure analysis. The second substudy investigated the resilience of the welds in a Langendorf-type pulsatile pressure setup, monitoring the number of failed vessels. The type of failure (cohesive vs adhesive) was confirmed by electron microscopy, and thermal damage was assessed histologically. The third substudy compared breaking strength of aortic repairs made with PLGA and semisolid genipin solder (ssLAVR) to repairs made with BioGlue. RESULTS: ssLAVA with 11 lasing spots and PLGA scaffold yielded the highest bursting pressure (923 ± 56 mm Hg vs 703 ± 96 mm Hg with PCL ssLAVA; P = .0002) and exhibited the fewest failures (20% vs 70% for PCL ssLAVA; P = .0218). The two failed PLGA ssLAVA arteries leaked at 19 and 22 hours, whereas the seven failed PCL ssLAVA arteries burst between 12 and 23 hours. PLGA anastomoses broke adhesively, whereas PCL welds failed cohesively. Both modalities exhibited full-thickness thermal damage. Repairs with PLGA scaffold yielded higher breaking strength than BioGlue repairs (323 ± 28 N/cm(2) vs 25 ± 4 N/cm(2), respectively; P = .0003). CONCLUSIONS: PLGA ssLAVA yields greater anastomotic strength and fewer anastomotic failures than PCL ssLAVA. Aortic repairs with BioGlue were inferior to those produced with PLGA ssLAVR. The results demonstrate the feasibility of ssLAVA/R as an alternative method to suture anastomosis or tissue sealant. Further studies should focus on reducing thermal damage.

Biodegradable polymer scaffold, semi-solid solder, and single-spot lasing for increasing solder-tissue bonding in suture-free laser-assisted vascular repair.

We recently showed the fortifying effect of poly-caprolactone (PCL) scaffold in liquid solder-mediated laser-assisted vascular repair (ssLAVR) of porcine carotid arteries, yielding a mean ± SD leaking point pressure of 488 ± 111 mmHg. Despite supraphysiological pressures, the frequency of adhesive failures was indicative of weak bonding at the solder-tissue interface. As a result, this study aimed to improve adhesive bonding by using a semi-solid solder and single-spot vs. scanning irradiation. In the first experiment, in vitro ssLAVR (n=30) was performed on porcine abdominal aorta strips using a PCL scaffold with a liquid or semi-solid solder and a 670-nm diode laser for dual-pass scanning. In the second experiment, the scanning method was compared to single-spot lasing. The third experiment investigated the stability of the welds following hydration under quasi-physiological conditions. The welding strength was defined by acute breaking strength (BS). Solder-tissue bonding was examined by scanning electron microscopy and histological analysis was performed for thermal damage analysis. Altering solder viscosity from liquid to semi-solid solder increased the BS from 78 ± 22 N/cm(2) to 131 ± 38 N/cm(2) . Compared to scanning ssLAVR, single-spot lasing improved adhesive bonding to a BS of 257 ± 62 N/cm(2) and showed fewer structural defects at the solder-tissue interface but more pronounced thermal damage. The improvement in adhesive bonding was associated with constantly stronger welds during two weeks of hydration. Semi-solid solder and single-spot lasing increased welding strength by reducing solder leakage and improving adhesive bonding, respectively. The improvement in adhesive bonding was associated with enhanced weld stability during hydration.

Optimization of suture-free laser-assisted vessel repair by solder-doped electrospun poly(ε-caprolactone) scaffold.

Poor welding strength constitutes an obstacle in the clinical employment of laser-assisted vascular repair (LAVR) and anastomosis. We therefore investigated the feasibility of using electrospun poly(ε-caprolactone) (PCL) scaffold as reinforcement material in LAVR of medium-sized vessels. In vitro solder-doped scaffold LAVR (ssLAVR) was performed on porcine carotid arteries or abdominal aortas using a 670-nm diode laser, a solder composed of 50% bovine serum albumin and 0.5% methylene blue, and electrospun PCL scaffolds. The correlation between leaking point pressures (LPPs) and arterial diameter, the extent of thermal damage, structural and mechanical alterations of the scaffold following ssLAVR, and the weak point were investigated. A strong negative correlation existed between LPP and vessel diameter, albeit LPP (484±111 mmHg) remained well above pathophysiological pressures. Histological analysis revealed that thermal damage extended into the medial layer with a well-preserved internal elastic lamina and endothelial cells. Laser irradiation of PCL fibers and coagulation of solder material resulted in a strong and stiff scaffold. The weak point of the ssLAVR modality was predominantly characterized by cohesive failure. In conclusion, ssLAVR produced supraphysiological LPPs and limited tissue damage. Despite heat-induced structural/mechanical alterations of the scaffold, PCL is a suitable polymer for weld reinforcement in medium-sized vessel ssLAVR.

Electrospun poly(ɛ-caprolactone) scaffold for suture-free solder-mediated laser-assisted vessel repair.

BACKGROUND AND OBJECTIVE: The addition of poly(lactic-co-glycolic) acid (PLGA) scaffolds to liquid solder-mediated laser-assisted vascular repair (sLAVR) has been shown to increase soldering strength significantly. Unfortunately, the fast degradation of PLGA is associated with adverse effects such as acidity of the degradation products. This study investigated the possibility of using electrospun poly(ɛ-caprolactone) (PCL) as reinforcement material in scaffold and solder-mediated LAVR (ssLAVR). MATERIALS AND METHODS: In vitro sLAVR of 10-mm arteriotomies (n = 62) was performed on 0.3- to 0.6-cm diameter porcine carotid arteries with a 670-nm diode laser. The solder contained 50% bovine serum albumin (BSA) and 0.1-0.7% methylene blue (MB) as a chromophore. The soldering strength was studied as a function of PCL-scaffold thickness, scaffold-fiber diameter, MB concentration, number of laser passes, and different sLAVR techniques. Leaking-point pressures (LPPs) were measured with a fluid-infusion technique. RESULTS: The highest mean ± SD LPP (749 ± 171 mm Hg) was produced by the ssLAVR modality that included the sheathing of the arteriotomy with 30 µL solder containing 50% BSA and 0.5% MB, followed by application of the PCL scaffold (mean ± SD thickness of 187 ± 9 µm and 14-µm fiber diameter) and irradiation with two consecutive continuous-wave laser passes. CONCLUSIONS: The study demonstrated the potential applicability of an electrospun PCL scaffold as reinforcement material in ssLAVR. Soldering strength was dependent on the scaffold physical properties, chromophore concentration, the number of laser passes, and the ssLAVR technique.