Author + information
- aBaylor University Medical Center, Dallas, Texas
- bBaylor Heart and Vascular Institute, Dallas, Texas
- cBaylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas
- dHeart Hospital Baylor Plano, Plano, Texas
- ↵∗Reprint requests and correspondence:
Dr. Peter A. McCullough, Baylor Heart and Vascular Institute, 621 North Hall Street, H030, Dallas, Texas 75226.
It has been long recognized that patients with end-stage renal disease (ESRD) have an approximate 10-fold increase in mortality compared to age-matched individuals in the general population (1). Approximately one-half of this mortality is attributable to cardiovascular disease in the large domains of coronary artery disease, valvular abnormalities, arrhythmias, and cardiomyopathy (2). Our understanding of “structural heart disease” among those with ESRD has come from autopsy studies describing abnormalities including increased cardiac and left ventricular (LV) mass, mitral and aortic calcium, and marked calcific deposits in atherosclerotic plaques in the coronary arteries, aorta, and peripheral arteries (Figure 1) (3,4). Morphological studies have also demonstrated high rates of pericardial disease (thickening and calcium) as well as myocardial hemosiderosis in ESRD. Physiological derangements over the course of many years, including pressure overload, volume overload, and derangements in myocyte function, also play a central role in the development of morphological abnormalities seen in ESRD. Cardiac ultrasonography has added to our understanding that these morphological changes have physiological consequences including impairment in LV systolic and diastolic function, chamber dilation and wall thickening, abnormal flow acceleration, and in some cases valvular stenosis (5). Coronary angiographic analysis has found in general that epicardial coronary arterial disease is more diffuse with more extensive calcium than those with normal renal function (1). The rate of coronary calcific deposition is more rapid than in the general population and is not reversible or able to be attenuated with any form of therapy we are presently aware of (6).
With this backdrop, Hickson et al. (7), in this issue of the Journal, have attempted to classify the findings from 12 years of cardiac echocardiograms obtained from 654 patients with ESRD, within 1 month before or 3 months after hemodialysis was initiated. Timing of the initiation of dialysis and the association with cardiac structural findings was explored in detail with a sensitivity analysis, and the authors concluded that the changes in the heart that were observed must have occurred during the course of chronic kidney disease (CKD) over many years and could not have been ascribed to the relatively small number of dialysis sessions incurred by this cohort. The 5-year survival in these patients was 38%, which is concordant with the 40% rate reported for the overall U.S. Renal Data System. This suggests there was little bias introduced by the restriction of cases to those with echocardiography results available (7,8). Their findings represent abnormalities in the heart that could be attributed to years of progressive CKD but not the effects of maintenance hemodialysis. They found that both LV and right ventricular (RV) dysfunction were associated with all-cause mortality over several years. Although readers may find these results completely expected, the authors went beyond these findings and analyzed 8 proposed criteria established by the Acute Dialysis Quality Initiative that would constitute “structural heart disease” among patients with ESRD (9). One or more of these echocardiographic criteria were present in 87% of subjects with 54% having 3 or more abnormalities. Left atrial dilation (55%), LV hypertrophy (37%), and LV diastolic impairment (54%) were most common among their findings. For the valves, mitral regurgitation (23%) and aortic stenosis (3%) were most prevalent. Any RV dysfunction was present in 27% of subjects, and moderate to severe RV dysfunction was present in 10%, suggesting that RV changes may have determinants that are different from those in left-sided failure, including chronic volume overload from systemic arteriovenous shunting via dialysis access grafts and fistulas. Hickson et al. (7) point out that RV failure can lead to LV dysfunction via ventricular interdependence, and importantly, this complication may be modifiable with greater attention to the location and size of the dialysis access and a better understanding of the magnitude of shunt volume and degree of recirculation during hemodialysis. Older age, coronary artery disease, heart failure, and higher comorbidity index anticipated structural heart disease as expected. Because structural heart disease was so common, it was not a binary independent predictor of events over follow-up. Both LV and RV systolic functions were independent determinants of survival (7). Importantly, patients with RV failure as a feature of their structural heart disease had the highest mortality of all patient groups.
This study adds to previously published reports in several ways. First, it demonstrated that proposed criteria for structural heart disease can in fact be systematically assessed by echocardiography and that most patients who begin dialysis have structural heart disease as a consequence of longstanding CKD, coronary disease, systemic hypertension, diabetes mellitus, CKD mineral and bone disorder (phosphate retention, hyperparathyroidism), anemia, and other abnormalities that develop over the course of CKD (10,11). Clearly these abnormalities cannot be ascribed to the use of the dialysis procedure itself or concomitant dialysis-related therapies. Second, both LV and RV systolic dysfunction (presumably as a consequence of or concomitant with the other abnormalities) are the dominant echocardiographic variables related to survival after dialysis has been initiated. Previous studies have relatively neglected the RV, and the present study highlights its importance in the understanding of risk for death in ESRD (1). Future research that focuses on these variables and their clinical consequences may give us insights into more favorable methods of dialysis, adjunctive therapy, or anticipatory use of devices that can help reduce the very high rates of mortality, particularly sudden death seen in this patient population.
↵∗ Editorials published in Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
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- Collins A.J.
- Hickson L.J.,
- Negrotto S.M.,
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- for the ADQI XI Workgroup
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group