Hemodialysis, a vital therapeutic intervention for individuals with end-stage renal disease (ESRD), relies on the establishment of an arteriovenous fistula (AVF) as the preferred vascular access [1]. While AVFs are highly valued for their longevity and reduced risk of infection, their impact on cardiac function in hemodialysis patients has drawn significant attention in recent years [2-4]. The creation of an AVF introduces profound hemodynamic changes in the cardiovascular system [5]. As arterial blood is redirected directly into venous circulation through the AVF, it results in augmented cardiac output. While the heart exhibits remarkable adaptive capabilities, sustained high blood flow associated with AVFs can place considerable stress on the cardiac muscles [6].

The alterations in cardiac hemodynamics prompted by AVFs raise important questions regarding the long-term consequences in hemodialysis patients. Understanding the impact of high-flow AVFs on cardiac function is crucial for optimizing patient care and improving overall outcomes [7-9]. This area of research has potential implications for dialysis treatment protocols, as well as for the development of strategies to minimize cardiac strain in hemodialysis patients with AVFs.

In this study, we aimed to explore the effect of high-flow AVFs on cardiac function in hemodialysis patients. Additionally, we investigate the influence of various factors, such as the type of AVF location and the patient’s baseline cardiovascular health, on the cardiac impact of AVFs.

Between June 2022 and September 2023, a longitudinal investigation was conducted at Rouhani Hospital of Babol University of Medical Sciences. This study aimed to explore the impact of high-flow AVF on cardiac function. The study screened 2,350 ESRD patients who received AVF creation for hemodialysis. Patients with hyperfunctioning fistula were also assessed. Furthermore, in accordance with the local center guidelines, routine echocardiography was performed every six months for all patients with high-flow AVF to monitor potential changes in cardiac function.

The study enrolled a cohort aged between 18 and 80 years who had undergone AVF creation and received thrice-weekly dialysis for a minimum of 12 months. AVF flow volume was measured three months after AVF maturation using a standardized protocol [10] employing duplex ultrasound with the GE Logiq E9 system from General Electric Healthcare, Wauwatosa, WI, USA, equipped with an 8 MHz linear transducer. The patients were placed in a supine position to facilitate accurate measurements. The mid-brachial artery served as the primary site for blood flow measurement because of its accessibility and reliability in assessing AVF characteristics. A 60° (56°-69°) angulation was meticulously controlled to ensure accurate measurements, whereas cross-sectional area determination was achieved by outlining the vessel lumens on the obtained images and employing specialized software for precise area calculations. The velocity within the mid-brachial artery was measured using pulsed-wave Doppler ultrasonography. During the flow volume calculations, the flow in the contralateral brachial artery was subtracted to isolate and accurately quantify AVF flow volume.

Individuals with a flow volume equal to or greater than 2,000 mL/min were eligible as high-flow fistula group for enrollment. Patients with a history of significant cardiac disease, recent myocardial infarction, cardiac surgery, or AVF-related complications, such as stenosis or thrombosis, requiring intervention during the study period were excluded. Baseline demographic data, including age, sex, duration of dialysis, comorbidities, cardiac function, and blood pressure, were assessed at baseline and at the end of the 12 months follow-up. Echocardiography was performed by an experienced cardiologist to evaluate the cardiac parameters, including left ventricular ejection fraction (LVEF), left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD), right ventricular end-diastolic dimension (RVEDD) and inferior vena cava diameter (IVCD).

Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Paired t-tests and Wilcoxon signed-rank tests were employed to analyze changes in cardiac parameters between baseline and the 12 months follow-up. In addition, a repeated-measures Analysis of Variance test was used to compare the range of changes in cardiac function parameters in the proximal and distal AVFs. A sample size of 100 patients was determined based on the ability to detect a clinically significant change in LVEF with 80% power and a significance level of 0.05. Ethical approval for the study was obtained from the Ethics Committee of Babol University of Medical Sciences (IR.MUBABOL.HRI.REC.1401.091), and all patients provided written informed consent prior to participation.

In this longitudinal analysis, we conducted an in-depth examination of a cohort of 100 patients undergoing chronic hemodialysis. These individuals had received regular dialysis treatment for a minimum of 12 months through a high-flow AVF at Rouhani Hospital. The study population was composed of 54 male and 46 female participants with an average age of 55.95±13.39 years and a mean body mass index of 24.71±3.43 kg/m². Among the comorbidities under investigation, diabetes emerged as the predominant condition, affecting 87% of the patients, followed by hyperlipidemia with a prevalence of 49%. Angiotensin II receptor blocker was the most frequently prescribed drugs used by 51% of the participants. Subsequently, calcium channel blockers and diuretics featured with usage rates of 35% and 34%, respectively. The location of AVFs showed a distribution of 58% brachio-cephalic, 25% radio-cephalic, and 17% snuffbox AVF (Table 1).

Table 1 . Demographic and baseline characteristics of studied patients (N=100).

Characteristic	Description
Sex	Male: 54, female: 46
Age (y)	55.95±13.39
BMI (kg/m2)	24.71±3.43
Comorbidities (%)
Diabetes	87
Hyperlipidemia	49
Liver failure	1
Hyperthyroidism	1
Medications (%)
Angiotensin II Receptor Blockers	51
Calcium Channel Blockers	35
Diuretics	34
Aldosterone Receptor Inhibitors	1
Arteriovenous fistula (%)
Brachio-cephalic	58
Radio-cephalic	25
Snuffbox AVF	17
Type of anastomosis (%)
Side to side anastomosis	52
End to side anastomosis	48

Values are presented as mean±standard deviation..

BMI, body mass index; AVF, arteriovenous fistula..

A comprehensive evaluation of various echocardiographic and hemodynamic parameters was conducted before and after the creation of the AVFs to assess the impact of high-flow AVFs on cardiac function. The results revealed significant changes in several key parameters. Specifically, the LVEF exhibited a notable reduction from 51.10%±5.39% prior to AVF creation to 47.50%±5.79% post-AVF creation (P<0.001), indicating a decrease in cardiac contractility. Moreover, there was a slight increase in the LAD from 32.39±3.93 mm to 32.56±4.32 mm after AVF creation (P=0.012), suggesting potential alterations in left atrial size. LVEDD significantly increased from 51.32±5.69 mm to 52.79±6.48 mm after AVF creation (P<0.001), pointing to left ventricular dilation. In contrast, the RVEDD exhibited a non-significant change from 33.76±4.79 mm to 33.85±4.91 mm (P=0.072). Finally, the IVCD showed a significant increase from 15.81±1.50 mm to 16.12±2.08 mm after AVF creation (P=0.017), indicating shifts in venous hemodynamics (Table 2).

Table 2 . Results of the echocardiographic and hemodynamic parameters (mean±SD) before and 12 months after arteriovenous fistula creation.

Echocardiographic parameters	Pre-fistulization	12 months after fistulization	Mean difference (95% CI)	P-value
LVEF (%)	51.10±5.39	47.50±5.79	3.600 (2.622 to 4.578)	<0.001
LAD (mm)	32.39±3.93	32.56±4.32	–0.17 (–0.3 to –0.03)	0.012
LVEDD (mm)	51.32±5.69	52.79±6.48	–1.47 (–1.97 to –0.96)	<0.001
RVEDD (mm)	33.76±4.79	33.85±4.91	–0.09 (–0.18 to –0.00)	0.072
IVCD (mm)	15.81±1.50	16.12±2.08	–0.31 (–0.56 to –0.05)	0.017

95% CI, 95% confidence interval; LVEF, left ventricular ejection fraction; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; RVEDD, right ventricular end-diastolic dimension; IVCD, inferior vena cava diameter..

Additionally, echocardiographic parameters were assessed to investigate the effect of AVF location, such as distal radio-cephalic, snuffbox and brachio-cephalic high-flow AVFs, on cardiac function. The results indicated the following changes:

LVEF: there was no significant difference in LVEF (%) between distal AVFs (radiocephalic or snuffbox AVFs) and brachio-cephalic AVFs prior to AVF creation (50.48±6.32 vs. 51.55±4.60, P=0.327). However, at 12 months after fistularization, a statistically significant decrease was observed in LVEF (%) in both groups, with a more pronounced reduction in the brachio-cephalic AVF group (49.17±7.15 vs. 46.29±4.24, P=0.014).

LAD: there were no significant differences in LAD (mm) between distal and brachio-cephalic AVFs pre-fistulization (32.33±4.11 vs. 32.43±3.83, P=0.903) and at 12 months after fistulization (32.48±4.40 vs. 32.62±4.29, P=0.870).

LVEDD: pre-fistulization, LVEDD (mm) showed no significant difference between distal and brachio-cephalic AVFs (50.02±5.21 vs. 52.26±5.89, P=0.052). However, at 12 months after fistulization, there was a significant increase in LVEDD (mm) in both groups, with a more pronounced dilation in the brachio-cephalic AVF group (50.07±5.40 vs. 54.76±6.52, P<0.001).

RVEDD: no significant differences were observed in RVEDD (mm) between distal and brachio-cephalic AVFs pre-fistulization (33.76±4.51 vs. 33.76±5.03, P=0.997) and at 12 months after fistulization (33.81±4.54 vs. 33.88±5.20, P=0.945).

IVCD: pre-fistulization, IVCD (mm) was significantly smaller in the distal AVF group than in the brachio-cephalic AVF group (15.02±1.35 vs. 16.38±1.34, P<0.001). At 12 months after fistulization, both groups showed a significant increase in IVCD, with the brachio-cephalic AVF group having a larger IVCD compared to the distal AVF group (15.26±2.07 vs. 16.74±1.87, P<0.001) (Table 3, Fig. 1).

Table 3 . Comparison of echocardiographic parameters (mean±SD) based on high-flow AVF location before and 12 months after AVF creation.

Echocardiography parameters	Radio-cephalic or snuffbox AVF	Brachio-cephalic AVF	P-value (t-test)	Eta squared	P-value
LVEF (%)				0.158	<0.001
Pre-fistulization	50.48±6.32	51.55±4.60	0.327
12 months after fistulization	49.17±7.15	46.29±4.24	0.014
LAD (mm)				0.001	0.731
Pre-fistulization	32.33±4.11	32.43±3.83	0.903
12 months after fistulization	32.48±4.40	32.62±4.29	0.870
LVEDD (mm)				0.225	<0.001
Pre-fistulization	50.02±5.21	52.26±5.89	0.052
12 months after fistulization	50.07±5.40	54.76±6.52	<0.001
RVEDD (mm)				0.005	0.468
Pre-fistulization	33.76±4.51	33.76±5.03	0.997
12 months after fistulization	33.81±4.54	33.88±5.20	0.945
IVCD (mm)				0.002	0.634
Pre-fistulization	15.02±1.35	16.38±1.34	<0.001
12 months after fistulization	15.26±2.07	16.74±1.87	<0.001

AVF, arteriovenous fistula; LVEF, left ventricular ejection fraction; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; RVEDD, right ventricular end-diastolic dimension; IVCD, inferior vena cava diameter..

Figure 1. Comparison of echocardiographic parameters before and 12 months after arteriovenous fistula creation between distal (radio-cephalic and snuffbox) and proximal (brachio-cephalic) arteriovenous fistulas. LVEF, left ventricular ejection fraction; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; RVEDD, right ventricular end-diastolic dimension; IVCD, inferior vena cava diameter.

Additionally, systolic blood pressure exhibited a substantial increase post-fistulization (132.49±16.42 vs. 146.60± 17.43 mmHg) (P<0.001). Similarly, diastolic blood pressure also registered a significant elevation following fistulization (79.98±8.40 vs. 83.33±9.68 mmHg) (P<0.001). In addition, there were no significant differences in the studied cardiac parameters according to the type of AVF anastomosis (side to side vs. end to side) (P>0.05).

High-flow AVFs in patients undergoing hemodialysis have been recognized for their influence on cardiac function [4]. The pivotal findings of our study encompass several notable observations following one year of high-flow AVF usage. These findings included a statistically significant decrease in LVEF, a slight but significant increase in LAD, a substantial increase in LVEDD, and an increase in IVCD. Each of these findings contributes to a comprehensive understanding of the impact of high-flow AVFs on cardiac function and has important clinical implications.

The observed reduction in LVEF could be explained by changes in the hemodynamics of the heart. High-flow AVFs significantly alter volume and pressure loads on the heart. The abrupt increase in preload, resulting from the augmented venous return due to the AVF, increases the amount of blood that the heart has to pump [3]. This increased volume load can lead to ventricular dilation, primarily affecting the left ventricle [11]. In contrast, the decreased afterload, secondary to reduced systemic vascular resistance caused by the AVF, can impact the heart’s ability to effectively eject this increased blood volume [6]. Several mechanisms could explain the observed decrease in LVEF. The most prominent of these is the impairment of myocardial contractility. The heart muscles may struggle to contract efficiently under new loading conditions. High-flow AVFs create an environment in which the heart must adapt to handle the higher blood volume and reduced resistance to ejection. Over time, this adaptation can lead to decreased contractility, subsequently reducing the LVEF [3,11-13]. Furthermore, high-flow AVFs have been shown to decrease subendocardial coronary perfusion, which can lead to myocardial ischemia and further contribute to the decrease in LVEF [14].

The slight increase in LAD and significant rise in LVEDD post-AVF creation suggest potential cardiac remodeling. This dilation could be a compensatory response to increased cardiac output demands, particularly considering the higher blood flow facilitated by the AVFs. Nevertheless, these changes underscore the need for vigilance in monitoring left atrial and ventricular dimensions in patients with high-flow AVFs [15,16]. The non-significant change in RVEDD could imply that the right ventricle remains less affected by the high-flow AVFs [17,18]. This could be due to the inherent differences in the ability of the right and left ventricles to adapt to abnormal loading conditions [3]. However, the impact of AVFs on right ventricular function might necessitate further investigation, particularly in a long-term context. The increase in IVCD suggests significant changes in venous hemodynamics following AVF creation. The high-flow AVFs can lead to alterations in venous return dynamics, potentially impacting the heart's filling patterns and preload of the heart.

Comparing our findings with those of previous related studies, we noted both similarities and differences between our findings and those of previous studies. For instance, the observed decrease in LVEF aligns with some earlier research [4,5,14,19], highlighting the consistent impact of high-flow AVFs on cardiac contractility. However, the extent of the cardiac changes may differ among studies. These distinctions might arise from variations in the study populations, AVF types, and duration of hemodialysis. Notably, the non-significant change in RVEDD is a point of differentiation in our findings compared to some previous research [20,21].

A comparative analysis of changes in echocardiographic parameters between high-flow AVFs located in the distal and proximal upper limbs revealed noteworthy disparities. Specifically, the LVEF reduction in brachio-cephalic AVFs was significantly more substantial than that in radio-cephalic or snuffbox AVFs. This finding aligns with the findings of a study conducted by Martínez-Gallardo et al. [22], in which the relationship between AVF location and the occurrence of new congestive heart failure was notably pronounced. Notably, the incidence of congestive heart failure was considerably higher in brachio-cephalic AVFs, standing at 40%, in comparison to the lower incidence of 8% observed in distal radio-cephalic AVFs. This observation has particular clinical significance, especially in hemodialysis patients who may be susceptible to heart failure.

This study has several limitations. While it included patients with high-flow AVFs (flow volume equal to or greater than 2,000 mL/min), the exact flow volume was not compared between the distal and brachio-cephalic AVFs. As a result, the brachio-cephalic AVFs may potentially exhibit a more substantial flow volume than the distal AVFs. It is recommended that more extensive study designs be conducted because the current study’s observational methodology may introduce confounding variables and because the 12-month follow-up period may not fully capture the long-term effects of high-flow AVF on cardiac function in hemodialysis patients. Additionally, because only one center supplied the sample, the results may not be as broadly relevant.

This study highlights the significant impact of high-flow AVFs on various echocardiographic parameters in patients undergoing hemodialysis. The observed changes in LVEF, left atrial and ventricular dimensions, and potential cardiac remodeling highlight the risk of developing cardiac failure in this patient population. Therefore, close monitoring of the cardiac function is imperative in individuals with high-flow AVFs to mitigate the risk of congestive heart failure. Additionally, consideration of the tolerability of distal AVFs in patients with ESRD and high-flow AVFs may offer a valuable clinical insight.

With special gratitude to the Research Department of Babol University of Medical Sciences that scientifically and financially supported this study as a vascular surgery thesis with proposal number 724133403.

None.

The authors have nothing to disclose.

Concept and design: PT, NZ. Analysis and interpretation: PT, NZ, AB. Data collection: PT, NZ, SG, FM. Writing the article: PT, NZ, SG, FM, AB. Critical revision of the article: PT, NZ. Final approval of the article: all authors. Statistical analysis: AB. Obtained funding: PT. Overall responsibility: NZ.