Effects of arteriovenous fistula formation on arterial stiffness and cardiovascular performance and function.

BACKGROUND: Native arteriovenous fistula (AVF) is the vascular access of choice and its use cf. catheters is associated with sustained reduction in mortality. This may be due to factors beyond dialysis catheter-associated sepsis. This study aimed to investigate the impact of AVF formation on the spectrum of cardiovascular factors that might be important in the pathophysiology of cardiovascular diseases in chronic kidney disease (CKD) patients. METHODS: We recruited 43 pre-dialysis patients who underwent AVF formation. Patients were studied 2 weeks prior to AVF operation and 2 weeks and 3 months post-operatively. Haemodynamic variables were measured using pulse wave analysis, carotid femoral pulse wave velocity (CF-PWV) by applanation tonometry and AVF blood flow by Doppler ultrasound. Bioimpedence analysis was performed and patients underwent serial transthoracic echocardiography. RESULTS: AVF formation was successful in 30/43 patients. Two weeks post-operatively, total peripheral resistance decreased (-17 ± 18%, P = 0.001), stroke volume tended to rise (12 ± 30 mL, P = 0.053) and both heart rate (4 ± 8 bpm, P = 0.01) and cardiac output (1.1 ± 1.5 L/min, P = 0.001) increased. Systolic and diastolic blood pressures (BPs) reduced (-9 ± 18 mmHg; -9 ± 10 mmHg; ≤ P = 0.006) and CF-PWV reduced (-1.1 ± 1.5 m/s, P = 0.004). Left ventricular ejection fraction (LVEF) increased (6 ± 8%, P < 0.001). All the observed changes were largely maintained after 3 months. No change in hydration status/body composition was observed. CONCLUSIONS: AVF formation resulted in a sustained reduction in arterial stiffness and BP as well as an increase in LVEF. Overall, post-AVF adaptations might be characterized as potentially beneficial in these patients and supports the widespread use of native vascular access, including older or cardiovascular compromised individuals.

Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease.

BACKGROUND AND OBJECTIVES: Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. RESULTS: Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality. CONCLUSIONS: CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.

Higher arteriovenous fistulae blood flows are associated with a lower level of dialysis-induced cardiac injury.

Native arteriovenous fistulae (AVF) remain the vascular access of choice for hemodialysis (HD). Despite being associated with superior long-term outcomes (cf. catheter use), little is known about the systemic hemodynamic consequences of AVFs. Repetitive myocardial injury (myocardial stunning) is an under-recognized common consequence of HD. The aim of this study was to examine the impact of AVF flow (Qa) on dialysis-induced cardiac injury. We studied 50 chronic HD patients. All patients underwent echocardiography (and subsequent quantitative offline analysis) at baseline, during and post dialysis, to assess left ventricular function and the development of regional wall motion abnormalities. Qa was measured using ionic dialysance. Patients were divided into Qa tertiles (<500, mean 291+/-101 mL/min, 500-1000, mean 739+/-130 mL/min and >1000, mean 1265+/-221 mL/min). There were no significant differences between the groups in terms of age, sex, diabetes, or resting ejection fraction. Patients with Qa>1000 mL/min had a lower prevalence of left ventricular hypertrophy (55% vs. 76%, P=0.01). Dialysis-induced myocardial stunning (seen in 65% of the patients studied) was significantly and sequentially reduced in those patients with higher Qas. This was seen in a lower number of segments and ventricular regions developing regional wall motion abnormalities, as well as a significantly reduced mean and cumulative percentage reduction in fractional shortening of those ventricular segments affected (-187+/-37%, -161+/-26%, and -101+/-25%, respectively, P=0.04). Relatively higher AVF flows appear to be associated with a lower level of observed HD-induced cardiac injury.

Hemodialysis-induced left ventricular dysfunction is associated with an increase in ventricular arrhythmias.

Conventional hemodialysis results in intradialytic cardiac ischemia in a significant proportion of patients. Segmental myocardial ischemia results in the development of left ventricular regional wall motion abnormalities. Sudden death is the most common cause of mortality in hemodialysis patients. This study looked to examine any association between the development of left ventricular regional wall motion and cardiac arrhythmias. Forty established hemodialysis patients had 24-hour Holter recordings, which commenced immediately before a dialysis session. Frequency of isolated ectopy was classified as a percentage of the total beats on the Holter monitor record. Ventricular arrhythmias were stratified according to the Lown classification. Classes 3 and above were taken as complex ventricular arrhythmias. Patients also underwent baseline and intradialytic echocardiography to assess the development of concurrent regional wall motion abnormalities. Premature ventricular complexes and complex ventricular arrhythmias were both more common during hemodialysis than in the subsequent monitored period. Patients who developed regional wall motion abnormalities (n = 27) had significantly more premature ventricular complexes during hemodialysis than afterward (p < 0.001). Patients with ischemic heart disease and left ventricular hypertrophy both had a higher frequency of premature ventricular complexes during hemodialysis than those without (p < 0.03 and p < 0.02, respectively). Cardiac arrhythmias are common in hemodialysis patients. The frequency of premature ventricular complexes is significantly higher during hemodialysis in patients who develop regional wall motion abnormalities and may be related to factors associated with demand ischemia.

Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow.

BACKGROUND AND OBJECTIVES: Hemodialysis is associated with hemodynamic instability, acute cardiac ischemia, and the development of regional wall motion abnormalities (RWMAs). This study used serial intradialytic H(2)(15)O positron emission tomography scanning to confirm that the development of dialysis-induced RWMAs was associated with reduction in myocardial blood flow (MBF). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four prevalent hemodialysis patients without angiographically significant coronary artery disease had measurements of MBF during standard hemodialysis and biofeedback dialysis. All patients underwent serial measurements of MBF using positron emission tomography. Concurrent echocardiography was used to assess left ventricular function and the development of RWMAs. Hemodynamic variables were measured using continuous pulse wave analysis. RESULTS: Mean prehemodialysis MBF was within the normal range. Global MBF was acutely reduced during hemodialysis. Segmental MBF was reduced to a significantly greater extent in areas that developed RWMAs compared with those that did not. Not all regions with reduced MBF were functionally affected, but a reduction in myocardial blood flow of >30% from baseline was significantly associated with the development of RWMAs. No significant differences in hemodynamic tolerability, RWMA development, or MBF between dialysis modalities were observed. CONCLUSIONS: Hemodialysis is associated with repetitive myocardial ischemia, which, in the absence of coronary artery disease, may be due to coronary microvascular dysfunction. Stress-induced segmental left ventricular dysfunction correlates with matched reduction in MBF. Functional poststress recovery is consistent with myocardial stunning induced by hemodialysis. This process may be important in the development of heart failure in long-term hemodialysis patients.