Incidence and Predictors of Acute Coronary Syndrome in Patients on Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis. Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up. Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors. Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome.

Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.

BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.

Association of Dysfunction of Vascular Access for Hemodialysis With Major Adverse Cardiovascular Events　- A Group-Based Trajectory Model Analysis.

BACKGROUND: An unconventional risk factor, "dysfunction of hemodialysis vascular access", was demonstrated to be associated with subsequent major adverse cardiovascular events (MACE) in our previous study. However, applying this suggestion in a clinical scenario may be not intuitive. A group-based trajectory model was applied to further recognize those patients with the highest risks for MACE.Methods and Results:In a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9,711 cases that developed MACE in the stage of stable maintenance dialysis, and 19,422 randomly selected controls matched to cases on age, gender and duration of dialysis. Events of vascular access dysfunction in the 6-month period before MACE for cases and index dates for controls were evaluated. By group-based trajectory modeling, patients according to their counts of vascular access dysfunction in each month over the 6-month period prior to MACE or index dates were categorized. There were 26,744 patients in group 1 (no dysfunction), 650 in group 2 (escalating dysfunction) and 1,739 in group 3 (persistent dysfunction). Logistic regression analysis indicated that patients in group 3 had the highest chance of subsequent MACE (odds ratio 2.47, in comparison with group 1) after controlling for all the available potential confounders. CONCLUSIONS: Uninterrupted clusters of vascular access dysfunction are associated with a higher risk of subsequent MACE.

Dialysis Arteriovenous Fistula Failure and Angioplasty: Intimal Hyperplasia and Other Causes of Access Failure.

The arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients' morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty continues to be the gold-standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a 2-stage brachiobasilic AVF that was complicated by failure 4 months after creation. An angiogram showed multiple juxta-anastomotic and midfistula stenotic lesions. Percutaneous transluminal angioplasty was successful in assisting maturation and subsequently cannulating the AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis because biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH and highlights the need for more therapeutic options to reduce AVF failure rate.

Elastin is a key regulator of outward remodeling in arteriovenous fistulas.

OBJECTIVES: Maturation failure is the major limitation of arteriovenous fistulas (AVFs) as hemodialysis access conduits. Indeed, 30-50% of AVFs fail to mature due to intimal hyperplasia and insufficient outward remodeling. Elastin has emerged as an important determinant of vascular remodeling. Here the role of elastin in AVF remodeling in elastin haplodeficient (eln(+/-)) mice undergoing AVF surgery has been studied. METHODS: Unilateral AVFs between the branch of the jugular vein and carotid artery in an end to side manner were created in wild-type (WT) C57BL/6 (n = 11) and in eln(+/-) mice (n = 9). Animals were killed at day 21 and the AVFs were analyzed histologically and at an mRNA level using real-time quantitative polymerase chain reaction. RESULTS: Before AVF surgery, a marked reduction in elastin density in the internal elastic lamina (IEL) of eln(+/-) mice was observed. AVF surgery resulted in fragmentation of the venous internal elastic lamina in both groups while the expression of the tropoelastin mRNA was 53% lower in the eln(+/-) mice than in WT mice (p < .001). At 21 days after AVF surgery, the circumference of the venous outflow tract of the AVF was 21% larger in the eln(+/-) mice than in the WT mice (p = .037), indicating enhanced outward remodeling in the eln(+/-) mice. No significant difference in intimal hyperplasia was observed. The venous lumen of the AVF in the eln(+/-) mice was 53% larger than in the WT mice, although this difference was not statistically significant (eln(+/-), 350,116 ± 45,073 µm(2); WT, 229,405 ± 40,453 µm(2); p = .064). CONCLUSIONS: In a murine model, elastin has an important role in vascular remodeling following AVF creation, in which a lower amount of elastin results in enhanced outward remodeling. Interventions targeting elastin degradation might be a viable option in order to improve AVF maturation.

Longitudinal micro-incision creation prior to balloon angioplasty for treatment of arteriovenous access dysfunction in a real-world patient population: 6-month cohort analysis.

INTRODUCTION: Routine hemodialysis depends on well-functioning vascular access. In the event of vascular access dysfunction, percutaneous transluminal balloon angioplasty (PTA) is conducted to restore patency. Although an angioplasty procedure can provide an excellent immediate result by opening the access to allow dialysis to continue, the long-term patency rates are less than satisfactory. The goal of this study was to assess the outcomes of patients who underwent a novel vessel preparation via longitudinal, controlled-depth micro-incisions prior to PTA. METHODS: This multicenter, prospective, observational registry enrolled hemodialysis patients scheduled to undergo PTA of their arteriovenous fistula or graft due to clinical or hemodynamic abnormalities. A primary endpoint was anatomic success, defined as angiographic confirmation of <30% residual stenosis post-procedure without an adverse event. Additional assessments included device technical success, clinical success, freedom from target lesion revascularization, target lesion primary patency, and circuit primary patency at 6 months. FINDINGS: A total of 148 lesions were treated with the FLEX Vessel Prep™ System (FLEX VP) prior to PTA in 114 subjects at eight clinical sites. Target lesions were 21 ± 25 mm in length with mean pre-procedure stenosis of 75.2% ± 4.7%. Five procedural complications were recorded without serious adverse events. Two subjects did not complete the follow-up evaluation. Target lesion primary patency across all subjects at 6-months was 62.2% with mean freedom from target lesion revascularization of 202.7 days. Target lesion primary patency and freedom from target lesion revascularization for AVF cases (n = 72) were 67.5% and 212.9 days, respectively. Target lesion primary patency and freedom from target lesion revascularization for AVGs (n = 42) were 52.4% and 183.3 days, respectively. In cases treating AVF cephalic arch stenosis (n = 25), 6-month target lesion primary patency was 70.6% and freedom from target lesion revascularization was 213.4 days. DISCUSSION: This FLEX-AV registry demonstrates safety and effectiveness, notably in the cephalic arch and AVGs, when FLEX VP is used prior to PTA for treatment of vascular access dysfunction in a population of end-stage renal disease subjects.

Central vein stenosis in hemodialysis vascular access: clinical manifestations and contemporary management strategies.

Central venous stenosis is a significant and frequently encountered problem in managing hemodialysis (HD) patients. Venous hypertension, often accompanied by severe symptoms, undermines the integrity of the hemodialysis access circuit. In central venous stenosis, dialysis through an arteriovenous fistula is usually inefficient, with high recirculation rates and prolonged bleeding after dialysis. Central vein stenosis is a known complication of indwelling intravascular and cardiac devices, such as peripherally inserted central catheters, long-term cuffed hemodialysis catheters, and pacemaker wires. Hence, preventing this challenging condition requires minimization of central venous catheter use. Endovascular interventions are the primary approach for treating central vein stenosis. Percutaneous angioplasty and stent placement may reestablish vascular function in cases of elastic and recurrent lesions. Currently, there is no consensus on the optimal treatment, as existing management approaches have a wide range of patency rates.

Atypical presentation of fistula dysfunction due to brachial arterial embolization mimicking stroke.

Vascular access thrombosis is an important complication with great impact on access patency and, consequently, on a patient's quality of life and survival. We report the case of a 73-year-old woman with chronic kidney disease on hemodialysis with a radiocephalic arteriovenous fistula on the right arm that was brought to the emergency department with decreased strength in her right arm, ipsilateral hypoesthesia and facial hemi-hypoesthesia. The patient was given a brain computed tomographic scan that did not confirm suspicion of stroke. On re-examination, the patient had new-onset pain at arteriovenous fistula level, and her right arm was cold and pale. The nephrology department was called for arteriovenous fistula evaluation. On physical examination, her forearm fistula had a decreased thrill and arm elevation exacerbated its paleness. A bedside ultrasound was performed for arteriovenous fistula assessment. Doppler ultrasound revealed: partial thrombosis at brachial bifurcation, a flow of 80-105 mL/min at brachial artery level and a radial artery with a damped waveform. Anastomosis and draining vein were permeable. In this case, the diagnosis of acute embolic brachial artery occlusion was made by a fast bedside ultrasound evaluation. The patient underwent thromboembolectomy with Fogarty technique, recovering fistula thrill, radial and cubital pulses. Thromboembolism of the fistula feeding artery is a rare cause of vascular access thrombosis and it is rarely mentioned in the literature. In this report, failure to recognize the upper limb ischemia would have led to delayed treatment, potentially resulting in the fistula's complete thrombosis and further limb ischemia. We highlight the importance of a diagnosis method like Doppler ultrasound, which allows for rapid evaluation at the patient's bedside.

An unusual spontaneous recanalization by multiple palmar arteriovenous connections of a chronically occluded radiocephalic hemodialysis fistula.

Preservation of a vascular access is crucial in the management of hemodialysis patients. In this regard, percutaneous transluminal angioplasty (PTA) is an effective tool if performed after an adequate understanding of preliminary fistulograms. The present case showed a chronic dysfunction of a radial-cephalic arteriovenous fistula (AVF) due to arterial occlusion and partially relieved by the spontaneous development of multiple small arteriovenous connections in the palmar region of the hand. This dense network had been so far able to ensure a sufficient retrograde blood flow for an effective hemodialytic performance. The angioplasty of the post-anastomotic stenotic segment of the radial artery was effective in restoring this neoformed AVF patency.

The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty.

Haemodialysis vascular access (VA) dysfunction is a major cause of morbidity in haemodialysis (HD) patients. Primary venous outflow occlusion and restenosis after percutaneous transluminal angioplasty (PTA) are two major obstacles for the long-term use of dialysis VA. It remains unclear whether oxidative stress markers can be used as predictors for thrombotic occlusion of VA and progressive stenosis dysfunction demanding PTA. All routine HD patients at one teaching hospital participated in this study including ankle-brachial index (ABI) examinations and serum oxidative stress markers. The serum oxidative stress markers (high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-2 (MMP-2), MMP-9, homocysteine, asymmetrical dimethylarginine (ADMA), nitrate oxidase (NO), tumour necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-1ß (IL-1ß), and transforming growth factor-ß (TGF-ß)) were measured using immunosorbent assays in 159 HD patients (83 men and 76 women; mean age: 65 ± 12 years). The participants met the following criteria: (1) received regular HD treatment for at least 6 months, without clinical evidence of acute or chronic inflammation, recent myocardial infarction, unstable angina or circulatory congestion; and (2) received an arteriovenous fistula (AVF)/arteriovenous graft (AVG: polytetrafluoroethylene, PTFE) as the current VA for more than 6 months, without interventions within the last 6 months. All the participants were followed up clinically for up to 12 months to estimate the amount of primary thrombotic occlusion and VA dysfunction demanding PTA. During the 12-month observation, 24 patients (15.1%) had primary thrombotic occlusion of VAs. Another 24 patients (15.1%) required PTA because of clinical dysfunction of access. Additionally, during the follow-up period, restenosis occurred in 12 patients (50% of 24 patients). The access types of arteriovenous grafts (AVGs) and a diagnosis of peripheral arterial occlusive disease (PAOD) were two strong predictors for acute thrombotic events of VA (hazard ratio (HR): 16.93 vs. 2.35; p < 0.001 vs. 0.047). Comparing dysfunctional with non-dysfunctional VAs, up to 27.7% of patients with high levels of ADMA (>0.6207 µM, N = 65) received required PTA compared with 4.4% of those with low levels (≤0.6207 µM; N = 90; p < 0.001). In multivariate analysis, the plasma baseline levels of ADMA independently conferred nearly 4.55 times the risk of primary stenotic dysfunction of HD VA (HR: 4.55; 95% confidence interval: 1.20 to 17.26; p = 0.026). In conclusion, our findings suggest the role of ADMA in the development of symptomatic VA dysfunction. Additionally, PAOD severity can be used in clinical practice to predict whether acute thrombotic occlusion of VA will easily occur in HD patients.

Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction.

Hemodialysis vascular access dysfunction is a common and intractable problem in clinical practice with no definitive therapy yet available. As a key mediator of vascular and cardiac maladaptive remodeling, mineralocorticoid receptor (MR) plays a pivotal role in vascular fibrosis and intimal hyperplasia (IH) and is potentiated locally in hemodialysis vascular access following diverse injuries, like barotrauma, cannulation and shear stress. MR-related genomic and non-genomic pathways are responsible for triggering vascular smooth muscle cell activation, proliferation, migration and extracellular matrix overproduction. In endothelial cells, MR signaling diminishes nitric oxide production and its bioavailability, but amplifies reactive oxygen species, leading to an inflammatory state. Moreover, MR favors macrophage polarization towards a pro-inflammatory phenotype. In clinical settings like post-angioplasty or stenting restenosis, the beneficial effect of MR antagonists on vascular fibrosis and IH has been validated. In aggregate, therapeutic targeting of MR may provide a new avenue to prevent hemodialysis vascular access dysfunction.

Cephalic Arch Stenosis: Location of Stenosis in Indian Hemodialysis Patients.

The cephalic vein is formed over the "anatomical snuff box" and joins the axillary vein just below the clavicular level. The definition of cephalic arch is varied. In the radiology literature, it is defined as the central perpendicular portion of the cephalic vein as it traverses the deltopectoral groove and joins the axillary vein. The possible etiologies of cephalic arch stenosis are numerous. This study aimed to identify patients with cephalic arch stenosis and to discern the domain site of stenosis. This is a retrospective case series of patients who had an arteriovenous fistula with dysfunction of access and ipsilateral upper-limb edema. The clinical features of the access dysfunction were strong pulse due to increased pressure, weak thrill due to poor proximal flow, high static pressure, or decreased dialysis efficiency. All these 25 patients underwent computed tomography (CT) angiogram. The CT angiographic findings revealed cephalic arch stenosis and stenosis in 13 patients (52%). domain IV was slightly more affected than other domains of cephalic arch.

Numerical evaluation and experimental validation of vascular access stenosis estimation.

Vascular access dysfunction commonly occurs in hemodialysis patients. Regularly monitoring and evaluating the vascular access condition is an important issue for these diseased patients. The objective of this study was to identify acoustic parameters and hemodynamics that related to changes in the stenosis of vascular access. In-vitro experimental circulation system offered pulsatile and physiological condition to simulate the arteriovenouse access in hemodialysis patient. We created the environments of various degrees of stenosis (DOS) inside the arteriovenouse access to simulate the stenotic conditions in patients. And we also used the computational fluid dynamics (CFD) to simulate the pressure distribution, primary axial velocity distribution, and secondary flow distribution in the same various DOS and boundary condition. There are two findings, one is recorded the bruit which caused by the fluctuation of fluid in different severe stenosis, the other is described the correlation between bruit and hemodynamic parameters. Experimental results show the time constants have linear regression with a positive correlation as the degree of stenosis (DOS) increases. Finally, in contrast to CFD computerized analysis and acoustic methods, the proposed parameter provides a feasibility index for evaluating the risk of AVG dysfunction in on-line/real time analysis.

Numerical evaluation and experimental validation of vascular access stenosis estimation.

Vascular access dysfunction commonly occurs in hemodialysis patients. Regularly monitoring and evaluating the vascular access condition is an important issue for these diseased patients. The objective of this study was to identify acoustic parameters and hemodynamics that related to changes in the stenosis of vascular access. In-vitro experimental circulation system offered pulsatile and physiological condition to simulate the arteriovenouse access in hemodialysis patient. We created the environments of various degrees of stenosis (DOS) inside the arteriovenouse access to simulate the stenotic conditions in patients. And we also used the computational fluid dynamics (CFD) to simulate the pressure distribution, primary axial velocity distribution, and secondary flow distribution in the same various DOS and boundary condition. There are two findings, one is recorded the bruit which caused by the fluctuation of fluid in different severe stenosis, the other is described the correlation between bruit and hemodynamic parameters. Experimental results show the time constants have linear regression with a positive correlation as the degree of stenosis (DOS) increases. Finally, in contrast to CFD computerized analysis and acoustic methods, the proposed parameter provides a feasibility index for evaluating the risk of AVG dysfunction in on-line/real time analysis.

Experimental and Numerical Analysis of the Bulk Flow Parameters Within an Arteriovenous Fistula.

The creation of an arteriovenous fistula for hemodialysis has been reported to generate unstable to turbulent flow behaviour. On the other hand, the vast majority of computational fluid dynamic studies of an arteriovenous fistula use low spatial and temporal resolutions resolution in conjunction with laminar assumptions to investigate bulk flow and near wall parameters. The objective of the present study is to investigate if adequately resolved CFD can capture instabilities within an arteriovenous fistula. An experimental model of a representative fistula was created and the pressure distribution within the model was analysed for steady inlet conditions. Temporal CFD simulations with steady inflow conditions were computed for comparison. Following this verification a pulsatile simulation was employed to assess the role of pulsatility on bulk flow parameters. High frequency fluctuations beyond 100 Hz were found to occupy the venous segment of the arteriovenous fistula under pulsatile conditions and the flow within the venous segment exhibited unstable behaviour under both steady and pulsatile inlet conditions. The presence of high frequency fluctuations may be overlooked unless adequate spatial and temporal resolutions are employed. These fluctuations may impact endothelial cell function and contribute to the cascade of events leading to aggressive intimal hyperplasia and the loss of functionality of the vascular access.

Is ionic dialysance useful for early detection of vascular access dysfunction? Six illustrative cases.

Continuous ionic dialysance monitoring is a useful clinical tool to determine the dialysis dose in real time in each hemodialysis session. We followed up 49 patients for 16 months. Six patients with a Kt reduction of ≥20% in >3 consecutive hemodialysis sessions were identified. Fistulography demonstrated significant stenosis in all 6 patients. Angioplasty was performed in 5 with an excellent angiographic result and optimal Kt levels were restored. Unexplained and persistent Kt reduction in patients with stable chronic kidney disease under hemodialysis could represent, together with an accurate vascular access examination, a practical and additional indirect method for the early detection of vascular access dysfunction.