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
- dThe Heart Hospital, Plano, Texas
- ↵∗Reprint requests and correspondence:
Dr. Peter A. McCullough, Baylor Heart and Vascular Institute, 621 North Hall Street, H030, Dallas, Texas 75226.
Investigators have long recognized that renal function and cardiac performance are integrally linked through hemodynamic, neural, humoral, cell signaling, proteomic, and metabolomic pathways (1). Among risk factors for the development of heart failure (HF), chronic kidney disease (CKD) is the most powerful because it contributes to the three fundamental mechanisms of left ventricular failure: 1) pressure overload; 2) volume overload; and 3) cardiomyopathy (2). When CKD progresses to end-stage renal disease (ESRD), these three mechanisms driving HF become more difficult to control because patients undergoing dialysis have on average higher blood pressures; poor volume control only partially addressed by thrice weekly hemodialysis in most cases; and a well-described form of cardiomyopathy characterized by severe left ventricular hypertrophy, marked cardiac fibrosis, reduced capillary density, and calcific deposits on the mitral and aortic valves (3). None of the goal-directed medical or device therapies proven to reduce HF-related hospitalization and cardiovascular death in the general population with HF have been demonstrated to be effective in patients with ESRD (4). This reason is that randomized trials have not been performed, and when these interventions are evaluated in nonrandomized studies, they appear to have a reduced benefit and a worse safety profile. For example, although observational data suggest that angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and mineralocorticoid antagonists could improve survival in ESRD, these agents are associated with greater degrees of hypotension and hyperkalemia than in patients in the general population with HF (5,6). Similarly, despite high rates of sudden death in patients with ESRD, implantable cardioverter-defibrillators have higher defibrillation thresholds in ESRD, greater risks of infection, and lesser degrees of efficacy than in the general population with HF (7,8).
With this backdrop, Pandey et al. (9) report, in this issue of JACC: Heart Failure, from the American Heart Association Get With the Guidelines–Heart Failure Program on rates of guideline-directed therapies in patients with HF with reduced left ventricular ejection fraction. These investigators compare the general population with HF with the following groups: patients with normal renal function (presumably estimated glomerular filtration rate >90 ml/min/1.73 m2); patients with renal insufficiency (presumably estimated glomerular filtration rate ≤90 ml/min/1.73 m2); and patients with ESRD, of whom 98.3% were undergoing hemodialysis (9,10). The major findings were from the initial study period to the final year, 2014 (study period possibly as long as 9 years): increases in use of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists at discharge of 16.3%, 38.1%, and 21.3% in the groups with normal renal function, renal dysfunction, and ESRD, respectively. Similarly, the increases in rates of evidence-based beta-adrenergic receptor blockade were 6.9%, 5.3%, and 13.0% for the same groups, respectively. Rates of implantable cardioverter-defibrillator use substantially increased by 63.8%, 78.2%, and 61.1% for the same groups, respectively. Finally, the increases in rates of “defect-free” care were 63.3%, 60.9%, and 80.9%, respectively. The groups with smaller relative increases started from higher baseline rates of compliance. Thus, our conclusions are much different from those of Pandey et al. (9) in that these data suggest, over a relatively short period of time, a large and substantial shift in evidence-based therapies in all three groups, with the groups with renal dysfunction and ESRD catching up to some degree to the group with normal renal function. Despite these advances, the group with normal renal function had absolutely no change in mortality or HF-related hospitalization rates, which were 32% and 33%, respectively, in 2005 and were completely unchanged for both events in 2012. Unsurprisingly, the absolute rates of events were higher in patients with renal dysfunction and in those with ESRD but were also unchanged from the earlier to the later years.
The critical observations from this report really are about the disconnect between guideline-directed therapies and outcome. Despite marked increases in the use of guideline-directed therapies over a short period of time, these therapies appear to have had absolutely no impact on HF-related hospitalization or death irrespective of renal function. Although HF with reduced left ventricular ejection fraction can be a very different disease in patients with normal renal function compared with patients with ESRD, these data are disappointing in that the group with normal renal function should have demonstrated markedly improved outcomes from 2005 to 2012 (2). It is possible that the program captures very ill patients with repeated hospitalizations over a very short period of time and that for such patients with Class 4 disease, it may be too late for longer-term medical and device therapies (11). Post-discharge medications and adherence data were not captured. Additionally, the adequacy of dialysis and volume control was a critical issue that could not be captured in this study (12). End-of-life decisions and withdrawal of care could have also played a role, and in these cases the use of evidence-base therapies documented at discharge may not have had any impact in a hospice or terminal care environment. Finally, the 1 year mortality rate of ≥50% in patients with renal dysfunction and ESRD may reflect modes of sudden death that are not amenable to implantable cardioverter-defibrillator or medical therapy, and in these groups, further research is needed to understand the final pathway to death (13).
In summary, we are disappointed in the lack of translation from improved rates of evidence-based therapies in HF with reduced ejection fraction to an improvement in outcomes in all patients with HF, not just patients with kidney disease. We have more work ahead of us in understanding the principles of population health and disease management in HF, with the ultimate goal of reduced rates of hospitalization and death, a goal that was not met in this program.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the author and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to this paper to disclose.
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