Hemodialysis-Induced Cardiac Dysfunction Is Associated with an Acute Reduction in Global and Segmental Myocardial Blood Flow

Patients

Four patients who were on long-term HD were recruited for a randomized crossover study. Coronary angiograms had been performed as part of routine clinical care (e.g., for workup for transplantation), and none of the patients needed clinical intervention. Angiographic results and remaining characteristics are shown in Table 1. All patients underwent dialysis via native arteriovenous fistulas, and all were anuric. Patients were excluded when they had significant symptomatic cardiac failure (NYHA ≥3) or experienced an acute coronary syndrome in the preceding 4 mo or had previously received a cardiac transplant or when it was not possible to obtain echocardiographic images of sufficient quality to allow meaningful analysis.

Study Protocol

On entry to the study, patients' dry weight and antihypertensive medications remained unchanged for the duration. Patients were then randomly assigned to two groups. Group A patients were commenced on standard thrice-weekly HD; group B patients started thrice-weekly dialysis with the Hemocontrol biofeedback system (BFD). Patients but not dialysis unit staff were blinded to the intervention. Both groups underwent 2 wk of the dialysis therapy after which patients attended their initial monitored dialysis session. β-Blocking agents and calcium antagonists were withdrawn 72 h before the study (because they are known to protect against myocardial stunning), and other antianginal medication were omitted on the day of the study. Patients were asked to avoid activities that might precipitate their angina for 12 h before the study and were excluded when they had experienced angina or used their glyceryl trinitrate spray within 4 h of commencement. After the conclusion of the first study, patients then crossed over to the other dialysis modality, thereby acting as their own control subjects. After 2 wk on the alternate modality, patients underwent a second monitored session on the same day of the week as the first study session.

For each monitored dialysis treatment, MBF was measured before dialysis, during treatment, at 2 and 4 h, and again 30 min into the recovery using H₂¹⁵O PET scanning. Serial echocardiography was performed at the same time points. Noninvasive hemodynamic monitoring of BP and heart rate was undertaken using a Finometer. For obtain baseline values, monitoring was started 30 min before commencement of dialysis. Predialysis blood tests were drawn immediately after insertion of access needles; after dialysis, levels were taken from the arterial line 10 s after reduction of blood pump speed to 50 ml/min. Single-pool Kt/V_urea values were calculated from before and after urea levels (22). The primary end point was the frequency of new LV RWMA during HD in relation to global and regional MBF. All patients gave informed consent before commencement, and ethical approval for the project was granted by Derbyshire Local Research Ethics Committee.

PET

Echocardiography

Two-dimensional echocardiography was performed in conjunction with perfusion scans at baseline and on HD at 120 and 240 min and at 30 min after dialysis had finished (recovery; 1.5 to 3.6 MHz 3S probe; Vivid 3; GE Medical Systems, Sonigen, Germany). Standard apical two-chamber and four-chamber views (to visualize the LV endocardial border in two planes at 90° to each other) were recorded for off-line digital analysis with Echo-CMS (MEDIS, Leiden, Netherlands) as described previously (29). Each apical view was divided into five segments, and percentage shortening fraction (SF) for the chords in each segment was averaged so that 10 regions of the left ventricle were assessed at each time point. New RWMA were defined as segments that demonstrated a decline in SF of >20% from baseline. When comparing dialysis modalities, the same time point was used in the second dialysis session.

Finometer

The use of the Finometer (Finapres Medical Systems, Arnhem, Netherlands) in dialysis patients has been described in detail elsewhere (20) and was used to monitor beat-to-beat heart rate and BP. Heart rate is represented as percentage change from baseline; however, BP is calibrated against brachial readings using a return-to-flow method, so absolute values are shown.

HD Details

Dialysis was performed using a Hospal Integra monitor (Hospal, Lyon, France). Both HD and BFD were performed using low-flux polysulphone dialyzers as per individual patients' usual prescription (LOPS 18/20; Braun Medical Ltd., Sheffield, UK) for 4 h. For both treatments, dialysate contained sodium 138 mmol/L, potassium 1 mmol/L, calcium 1.25 mmol/L, magnesium 5 mmol/L, bicarbonate 32 mmol/L, glucose 1 g/L, and acetate 3 mmol/L. All treatments were of 4 h duration, and anticoagulation was achieved with unfractionated heparin. Dialysate flow was 500 ml/min, and dialysate temperature was set at 37°C. For standard HD, dialysate sodium conductivity was set at 13.6 ms/cm. For BFD, limits for relative blood volume were set on an individual basis depending on measurements taken during the week before echocardiographic assessment. The prescribed input was total weight loss and final relative blood volume. Feedback was via ultrafiltration rate and dialysate conductivity for which limits were set at 13.0 and 14.0 ms/cm. For each session, net fluid removal was set on an individual basis according to ideal dry weight. Blood pump speed varied between 250 and 450 ml/min depending on patients' vascular access, but each individual patient had the same blood flow for his or her two monitored sessions. All patients underwent dialysis using arteriovenous fistulas.

Statistical Analyses

Results are expressed as mean ± SD if parametric or as median (interquartile range) if nonparametric, unless otherwise stated. Echocardiographic, BP, and hemodynamic data were analyzed using one-way ANOVA with a design for repeated measures and Bonferroni test to correct for multiple comparisons. For other data, either the paired t test or Wilcoxon rank sum test was used depending on normality of the distribution. An α error at P < 0.05 was judged to be significant.

Echocardiographic Data

Throughout the study, all patients were in sinus rhythm, and none had significant valvular disease or pulmonary hypertension. At 2 and 4 h, a total of 39 RWMA developed during both types of dialysis. There was no significant difference in the number of RWMA that developed between 2 and 4 h. At 30 min after dialysis (recovery period) compared with 4 h, 81% of RWMA had improved and 23% had regained normal function, confirming the presence of myocardial stunning in this group. There was no significant difference in either the number of RWMA or their severity in terms of SF between HD and BFD during dialysis or after the recovery period (P > 0.05 by ANOVA).

PET Data

All results were corrected for RPP; however, no significant difference was observed between corrected and noncorrected values at given time points. Previous studies have shown reduced baroreflex sensitivity and heart rate variability in this group (30); results shown are therefore noncorrected unless otherwise stated.

Global, mean predialysis MBF for both modalities was within the normal range. Global MBF was acutely reduced during dialysis and became progressively worse over time. There was some restoration of flow (but not complete) after the 30-min recovery period (see Figure 1).

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Figure 1.

Mean global myocardial blood flow (MBF) reduced significantly during dialysis from baseline with partial restoration in the recovery period.

Segmental MBF was reduced in 67 and 90% of regions at 2 and at 4 h, respectively. Three of the four patients had universal (100%) involvement with reduction of MBF in all segments during both dialysis modalities.

Between dialysis modalities (HD and BFD), baseline MBF was compared on an individual basis for each. There were no significant differences in three of the four patients (P > 0.05); however, one patient showed a significant improvement in resting MBF after the 2 wk of BFD. There were also no significant differences in MBF between dialysis modalities at 2 or 4 h, although when observing individual patients, one had a significant improvement in MBF at 4 h during BFD (P < 0.001) without any significant difference in MBF at baseline.

After the recovery period, there was an improvement in MBF in 85% of segments demonstrating partial but not complete restoration of blood flow after 30 min. There was a greater overall restoration of MBF after BFD compared with HD (P < 0.001; Figure 2).

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Figure 2.

Mean MBF during hemodialysis (HD) and biofeedback dialysis (BFD). No significant benefit was seen between dialysis modalities during treatment (^†P > 0.05); however, there was an improvement in MBF in the recovery period after BFD (*P < 0.001).

The development of RWMA demonstrated by echocardiography was significantly associated with a greater percentage reduction in MBF (−30 ± 27.7 versus −12.3 ± 12.3%; P = 0.001; Figure 3). Not all regions with reduced MBF were functionally affected; however, a reduction in MBF ≥30% from baseline (mean reduction of MBF in all regions 29%) was significantly associated with the development of RWMA (P < 0.01). Also, in areas where reduction in MBF was <30%, there was actually a mean overall increase in percentage wall motion (Figure 4).

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Figure 3.

The development of regional ventricular dysfunction as measured by regional wall motion abnormalities (RWMA; abnormal regions) was associated with a greater reduction in MBF from baseline than areas that maintained normal movement (normal regions; P = 0.001).

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Figure 4.

An MBF reduction of ≥30% was associated with a mean reduction in wall motion of −15.2%; however, an MBF reduction of <30% was associated with a mean increase in wall motion of 5% (P < 0.01).

Hemodynamic Data

Hemodynamic data are summarized in Figure 5. Mean systolic BP was maintained slightly higher during BFD (127 ± 10 mmHg) than HD (124 ± 12 mmHg; P < 0.05). There were no significant differences between diastolic BP and mean arterial pressure between HD and BFD. None of the patients had episodes of symptomatic or asymptomatic intradialytic hypotension. Heart rate increased throughout both modalities to a similar degree, with means of 6 ± 2% during HD and 6 ± 3% during BFD (NS).

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Figure 5.

(A) Overall mean BP between HD and BFD. BP was maintained higher on BFD (P < 0.05). (B) Heart rate increased similarly during both HD and BFD.

Laboratory Data

There were no differences in any of the biochemical parameters when the two types of dialysis were compared. Cardiac troponin-I levels were similar between the two modalities and did not change significantly after dialysis. Three of the four patients had normal cardiac troponin-I levels of <0.032 (Table 2).