Author + information
- Published online October 29, 2018.
- W.H. Wilson Tang, MD∗ (, )
- Kartik S. Telukuntla, MD and
- Kenneth A. Mayuga, MD
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. W.H. Wilson Tang, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue. Desk J3-4, Cleveland, Ohio 44195.
To provide optimal care for patients with acute decompensated heart failure (ADHF), insights into the degrees of congestion is key. In this issue of JACC: Heart Failure, Strobeck et al. (1) hypothesized that more precise and objective determination of volume status by blood volume analysis (BVA) would enable clinicians to better optimize diuretic regimens or care plans. They used an iodine-131−labeled human serum albumin indicator dilution technique to assess total blood volumes (TBVs), red blood cell volumes, and plasma volumes in a series of 245 consecutive admissions in 177 patients. First, the investigators pointed out that BVA measurements could provide insights that might prompt clinicians to reconsider routine diuretic therapy at the outset. Specifically, they observed that only 37% of patients who were believed to be volume overloaded by clinical assessment were actually hypervolemic according to BVA (TBV excess >10% vs. patient norm), although the details of how clinical assessments were made were lacking. Meanwhile, the investigators noted that same-day discharges occurred in 16.7% in this BVA-guided group, compared with only 1.4% in a propensity-matched control group obtained from Centers for Medicare and Medicaid Services data. These observations were concordant with the evolving concept that not all patients who present with signs and symptoms of ADHF have excess volume overload. Some patients might present with a reduction in splanchnic venous capacitance that generates ADHF signs and symptoms by acutely shifting blood from the veins into the circulating blood volume, thereby increasing preload without changing total body volume (2).
Although associative in nature, the investigators speculated that a possible explanation for this difference was that accurate determination of a near-euvolemic volume status might avoid unnecessary diuresis or over-diuresis that has the potential to drive adverse events. However, detailed clinical information or outcomes regarding this relatively euvolemic and/or early discharge cohort were not provided to corroborate these pathophysiological concepts. Regardless, these sobering findings, if true, are a reminder that bedside clinical assessment of volume status is challenging and might not be consistent nor accurate without objective measures like BVA, which arguably is the most believable finding of the study and a point that has been previously raised (3,4).
Next, the investigators highlighted the ability of BVA to guide diuresis goals by describing their innovative approach using serial peripheral hematocrit monitoring following BVA in patients who were deemed hypervolemic. Although largely theoretical and lacking direct demonstration of its reproducibility, the premise of this strategy was in concordance with previous associations that linked the ability to achieve hemoconcentration via effective diuresis with better clinical outcomes (5). Specifically, BVA can help calibrate an individual’s “normalized hematocrit,” thereby providing an individualized yardstick for diuretic goals to be targeted. This might indirectly explain why the BVA-guided group had a longer length of stay compared with that of the propensity-matched control subjects (7.3 days vs. 5.6 days; p < 0.001), because it might take longer to reach these euvolemic targets. But how exactly did the investigators execute this strategy? Were they the only people treating the patients or were there other physicians involved, and how did they ensure the treatment approaches were consistent? There were no consistent or standardized treatment protocol(s) described, and no detailed explanations of how the BVA and/or the serial hematocrit criteria matched the treatment strategies. Even BVA data were presented in aggregate forms, and the average differences in deficits to normalized hematocrit were quite small. Although some data on diuretic dosage changes (or lack thereof) after BVA were provided, the investigators did not outline in any detail how they chose the dose and route of diuretic (or other ADHF) therapy. Not knowing how the investigators made clinical decisions based on available BVA values and/or other parameters could challenge our abilities to design a consistent treatment algorithm as the intervention of interest to reproduce their findings.
In addition, it was unclear whether the course of clinical management would have been different in the absence of BVA information, or whether other factors (e.g., renal function, clinical status, or discharge logistics) would have taken into account in deciding the appropriate diuretic dosing. Would the same patient receive the same diuretic dosing and duration if BVA data were not available? As an aside, insights regarding the 12% of patients with anemia and 10% of patients with polycythemia among those with hypervolemia implied that true hematological abnormalities could also be detected by BVA, although the clinical benefits of their corrective treatments have yet to be established in this setting.
The investigators then attempted to generate a thought-provoking comparison of clinical outcomes between their BVA-guided cohort and those who underwent usual care management, as represented by 2,450 propensity-matched control subjects. They observed that BVA-guided management was associated with improved outcomes, namely, a lower 30-day readmission rate (12.2% vs. 27.7%; p < 0.001), lower 30-day mortality (2.0% vs. 11.1%; p < 0.001), and lower 1-year mortality (4.9% vs. 35.5%; p < 0.001) rates. It is important to emphasize that true comparison with clinical assessment was not possible in this retrospective analysis. The investigators did not provide any information regarding clinical assessment of the volume status of the patients. Clearly, the lower-than-expected rates of mortality and heart failure readmissions in the BVA-guided group might have magnified the between-group differences. This might also call into question whether the propensity-matching technique was adequate by using predominantly categorical variables in a large, heterogeneous administrative data set.
Despite the aforementioned limitations, the findings from Strobeck et al. are provocative. The premise that more objective assessments of volume status can better guide our clinical decision-making in ADHF is sound. However, the lack of blinding and randomization to overcome bias are inevitable limitations of this retrospective single-center case series with a historical and statistically matched comparison. The questions being raised here and the lack of clarity regarding the precise treatment algorithms might have rendered the investigators’ enthusiastic conclusions perhaps far too over-reaching. Such hypothesis-generating insights require independent validation with a randomized controlled trial design to demonstrate rigor and reproducibility of the findings. Translating in clinical practice, BVA is not an inexpensive test, and requires logistic solutions for its administration. Hence, beyond demonstrating incremental benefits by a BVA-guided approach in ADHF management, clinical adaptability and practical use of such a strategy will also depend on its cost-benefit assessment at a time when there is growing concerns regarding the increasing costs of health care.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Tang is supported by grants from the National Institutes of Health and the Ofﬁce of Dietary Supplements (R01DK106000, R01HL126827). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
- Strobeck J.E.,
- Feldschuh J.,
- Miller W.L.
- Fallick C.,
- Sobotka P.A.,
- Dunlap M.E.
- Miller W.L.
- Miller W.L.,
- Mullan B.P.