Patients with ESRD have an increased risk of premature cardiovascular mortality.1
In contrast to the general population, sudden, presumed arrhythmic, cardiac death, rather than myocardial infarction or heart failure, is the most common cause of death.22,23
Modification of traditional risk factors (eg, dyslipidemia) does not alter prognosis significantly,24,25
and reversal of LVH (the most common abnormality of uremic cardiomyopathy) is difficult.6
Alternative, potentially reversible, myocardial abnormalities have been sought to provide a target for intervention that may decrease cardiovascular death in this patient population.
Against this background, we prospectively assessed the effect of additional myocardial abnormalities and clinical history on survival in a cohort of ESRD patients with LVH. In particular, we investigated the prognostic effect of LAV, which has been shown previously using echocardiography as an independent predictor of death in dialysis patients.26
LAV can be calculated reliably from 2-dimensional echocardiography and CMR measurements.14,15
We restricted this study to patients with LVH to identify other potentially modifiable characteristics that predict death in patients with ESRD and established uremic cardiomyopathy.
Elevated LAV (higher than the median) was less common in male patients. This differs from previous studies that have shown removal of sex-related differences in LAV when corrected for body size. Neither sex nor BSA had an effect on survival in our analyses. There was no significant difference in cardiovascular disease history between groups (greater or less than median LAV). Furthermore, heart rate, LVEF, LVMi, and left ventricle chamber size (at end-diastole and end-systole) were similar in both groups. This suggests that left atrial size was not a marker of reduced diastolic filling time or impaired left ventricular systolic emptying.
In the survival analysis, higher LAV was significantly associated with poorer survival (A). Multivariate analysis also showed that increased LAV/BSA and presence of LVSD independently predicted death in ESRD patients with LVH. As previously demonstrated,17
a clinical history of ischemic heart disease was a significant independent predictor of death, and kidney transplantation was independently associated with significantly improved survival.27
These data confirm previous studies investigating LAV and survival.26
However, in previous studies no analyses were performed in patients with pre-existing myocardial abnormalities. We believe that the strength of this study lies with accurate assessment of LVMi using CMR imaging, which provides an accurate, volume-independent, and reproducible method of measuring LVM.9
In the present study, LAV was not significantly correlated with LVM, suggesting that increased LAV is not caused solely by impaired atrial emptying into a large, poorly compliant, left ventricle. In other patient populations, increased LAVs are considered to reflect the long-term effects of increased ventricular filling pressures.28
Thus, when filling pressures are increased, the atria (like the ventricles) will enlarge in response to pressure and chronic volume overload.29
LAV was not associated with diastolic dysfunction in our population as measured using E:A ratio. We did not obtain tissue Doppler or pulmonary venous blood flow velocity data to fully evaluate diastolic function, and it is likely that diastolic dysfunction is common in ESRD patients with LVH. Thus, we postulate that in ESRD patients with LVH, left atrial enlargement is caused largely by diastolic dysfunction and also chronic fluid overload due to expansion in intravascular volume.
A decrease in LAV has been achieved in patients with mitral valve disease and atrial fibrillation30,31
; however, its effect on overall prognosis is unknown. Whether tight control of fluid volume status in patients with ESRD similarly decreases LAV and mortality will require a controlled clinical trial.
We have previously shown that LVSD is associated with (often asymptomatic) ischemic heart disease and, in turn, poorer survival.4
This presumably is caused by occlusive large-vessel disease and inadequate growth of penetrating epicardial vessels in response to cardiac myocyte hypertrophy. Ventricular action potential propagation and recovery are impaired in the presence of LVH and LVSD, increasing the risk of ventricular re-entrant tachyarrhythmias.32,33
The prognostic benefits of improving systolic function of ESRD patients, using pharmacological approaches or modification of dialysis remain to be assessed.
In contrast to previous studies using echocardiography to assess left ventricular dimensions,34
higher LVMi was not a significant predictor of mortality in this cohort of patients. We have previously shown inaccuracies of echocardiography measurements in patients with ESRD,35
and it is likely that the use of CMR imaging to accurately assess myocardial mass will provide more reliable prognostic information in the future.
We accept that this study has some limitations. Patients recruited to this study were being assessed for kidney transplantation and may not be representative of all patients with ESRD. However, since these patients were considered healthy enough to be considered for a kidney transplant, we believe these results would be relevant to other patients with more significant comorbid conditions. In addition, we obtained limited information regarding ventricular diastolic function in our cohort and hopefully, as more detailed methods (eg, tissue Doppler) are utilized, these data will become available.
In conclusion, in ESRD patients with LVH, increased LAV and the presence of LVSD are independent predictors of death and may provide novel factors that may be amenable to modification to improve cardiovascular prognosis.