The Effects of Frequent Hemodialysis on Left Ventricular Mass, Volumes, and Geometry

Left ventricular (LV) remodeling is defined as ‘‘the genomic expression resulting in molecular, cellular, and interstitial changes that are manifested clinically as changes in size, shape, and function of the heart after cardiac injury” (1). In ESRD, LV remodeling manifests features of both concentric and eccentric LV hypertrophy, resulting from enlarged LV volumes and increased LV wall thickness (2). As we discuss here, LV mass can change because of a change in LV wall thickness, LV cavity size, or both. Increased LV mass, increased LV end-diastolic volume (LVEDV), and changes in LV geometry (LV mass/LVEDV) are all associated with poor prognosis in these patients (3,4). The Frequent Hemodialysis Network (FHN) trial is the first large-scale randomized controlled trial of frequent daily and nocturnal dialysis versus conventional dialysis (5). FHN investigators previously demonstrated that, compared with conventional hemodialysis, frequent daily hemodialysis results in a significantly greater reduction in LV mass, as determined by cardiac magnetic resonance imaging (MRI) (6). In this issue of CJASN, this group reports that frequent daily dialysis resulted in greater reductions in LV and right ventricular (RV) volumes without significant changes in LV geometry (7). In addition, reductions in both LV mass and LVEDV with frequent dialysis were significantly correlated with reductions in predialysis systolic BP (6,7). Here we present a brief overview of the literature on the effects of dialysis on LV remodeling, discuss likely mechanisms underlying the findings of the current study, and reflect on implications for future investigation.

Observational studies of frequent dialysis have shown salutary effects on BP (8–11) and LV mass index (12–15) and impressive survival rates (8,16). Moreover, LV hypertrophy has regressed in patients with ESRD who have baseline LV hypertrophy when aggressive management of BP and anemia was added to a thrice-weekly dialysis regimen (17,18). One such study shows that LV hypertrophy may regress without a change in relative wall thickness, another measure of LV geometry (18). In several studies, including the FHN trial, lowering BP was strongly associated with regression of LV hypertrophy (9,10,12–14). Prior studies of frequent dialysis that evaluated LV size in addition to mass did not specifically address LV geometry (10,13).

LV mass and volume are linked mathematically, physiologically, and empirically. Cardiac MRI is widely considered to be the gold standard for determining LV volume and mass, while M-mode echocardiography overestimates LV mass in patients with ESRD undergoing hemodialysis because of its geometric assumptions (19). In cardiac MRI, LV mass is calculated as myocardial volume multiplied by the specific density of the myocardium (20). Myocardial volume, in turn, is the difference between the end-diastolic epicardial volume and end-diastolic endocardial volume, excluding the papillary muscles (LVEDV). Thus, while MRI-determined LV mass is free of geometric assumptions, it remains mathematically dependent on LV cavity size (LVEDV). This dependence of MRI-determined LV mass on LVEDV has been confirmed empirically in patients with ESRD receiving hemodialysis (21). The strong correlation between LV mass and LVEDV in ESRD reflects the fact that LV hypertrophy is an adaptive response, at least in part, to chronic volume overload. In this issue of CJASN, this relationship between LV mass and LVEDV was reflected in the finding that most participants receiving frequent dialysis had reductions in both LV mass and LVEDV (Figure 4 in Chan and colleagues’ article) (7).

However, the findings of the current study suggest that the reduction in LVEDV is not purely the result of more effective management of cyclic changes in blood volume by frequent dialysis. Within the frequent dialysis group, interdialytic weight gain was associated with neither changes in LV mass (6) nor changes in LVEDV (7). These findings are similar to those of an earlier study that found no significant correlation between changes in total volume and changes in LVEDV (22). On the basis of this finding, we propose that changes in LVEDV induced by hemodialysis may not be related solely to changes in total blood volume, which would be reflected in changes in the interdialytic weight; decreased LVEDV may also result from a peripheral relocation of the blood volume away from the heart.

With frequent dialysis, there was a proportional decrease in both stroke volume (change, −10.58%) and LVEDV (change, −11.19%) (Table 2 in Chan and colleagues’ article) (7). Although this means that LV ejection fraction (stroke volume/LVEDV) did not change, we may infer that stroke work (stroke volume×LV systolic BP) decreased in the daily dialysis group (as opposed to the conventional group, in which stroke volume did not change) (Table 2 in Chan and colleagues’ article). Stroke work is the primary determinant of myocardial oxygen consumption. Therefore, the reduction in stroke work induced by frequent daily dialysis may lead to decreased myocardial oxygen consumption (2). Decreased myocardial oxygen demand, in turn, may improve myocardial oxygen supply-and-demand balance and may render the heart less vulnerable to ischemia-induced myocyte injury and ventricular arrhythmias. This is supported by results from a recent observational study showing reduced prevalence of myocardial stunning among patients receiving frequent dialysis (23).

The proportionate decrease in LV mass and LVEDV seen in the study by Chan et al. results in unchanged LV geometry. However, there are additional ways to evaluate LV remodeling. In a different study, Chan et al. examined gene expression in rat cardiomyocytes treated with plasma from patients who had undergone nocturnal or conventional dialysis. Cardiomyocytes treated with plasma from nocturnally dialyzed patients showed downregulation of proapoptotic and fibrotic genes, and upregulation of genes encoding proteins of cardiac contractility (24). In this same study, echocardiographic velocity vector imaging of patients on nocturnal dialysis showed better circumferential strain and torsion, suggesting improved LV systolic function (24). Future studies evaluating changes in gene expression, novel serologic biomarkers, or functional measures of LV performance may shed light on the effect of therapies aimed at reversing LV remodeling.

In addition to stratifying by LV mass, it might be useful to stratify future analyses by baseline LV geometry. In ESRD, LV mass/LVEDV may have opposite associations with prognosis, depending on whether the LV is dilated or not (4). In patients with a dilated LV, lower LV mass/LVEDV is associated with a worse prognosis; conversely, in those with normal LV cavity size, higher LV mass/LVEDV is associated with worse prognosis. In the former group, there is probably insufficient adaptive wall thickening to offset the higher LV wall stress of a dilated ventricle. Moreover, it remains uncertain whether patients with normal LVEDV at baseline benefit from further reduction in LVEDV; it is likely that in such patients, LV mass, not further reduction in LV volumes, would be associated with improved outcomes. In this issue of CJASN, it would have been interesting to test for a difference in the 1-year change in LV volumes between participants with dilated left ventricles at baseline and those with LV volumes in the normal range.

In comparison to the LV, the RV suffers from relative neglect in various pathologic states, such as congestive heart failure and ESRD. RV dysfunction is prevalent among patients with ESRD receiving hemodialysis (25). RV overload and dysfunction may contribute to LV dysfunction through interventricular dependence (26). The current study in this issue of CJASN is the first to report on the beneficial effect of frequent daily hemodialysis on RV end-diastolic volume (RVEDV) and, to a lesser extent, on RV end-systolic volume. Unlike changes in LVEDV, reductions in RVEDV were associated with both reductions in predialysis systolic BP and lower interdialytic weight gain. It is interesting to note that in this study, even conventional dialysis led to significant, but more modest, reductions in RVEDV and RV end-systolic volume. Although LV ejection fraction did not significantly change with frequent hemodialysis in this study, it would be interesting to investigate whether alleviating RV overload contributes to improved LV systolic and diastolic function as measured by advanced imaging techniques, such as LV myocardial strain or torsion (27,28).

In summary, findings from the FHN trial show that frequent hemodialysis results in reductions in LV mass and volumes and that these reductions are significantly correlated with reductions in predialysis systolic BP. The current study in this issue of CJASN enhances our understanding of the effects of frequent dialysis on the heart by providing a comprehensive evaluation of left and right ventricular volumes and of LV geometry. The implications of these changes in cardiac structure induced by frequent dialysis for LV diastolic function and susceptibility to myocardial injury are directions for future research.

Disclosures

None.