Author + information
- Marvin A. Konstam, MD∗ ( and )
- James E. Udelson, MD
- ↵∗CardioVascular Center, Tufts Medical Center, Box 108, 800 Washington Street, Boston, Massachusetts 02111
We appreciate the interest of Dr. Abdulhadi and colleagues in our paper (1) as well as their insightful comments regarding the impact of chronic kidney disease on the pathophysiology of dyspnea. We have several responses.
First, we would not conclude that tolvaptan had no effect on dyspnea in our population. The strength of any conclusions from our study is limited, given that we did not show significance for our primary endpoint, measured during the initial 24 h. However, we did see progressive separation in dyspnea scores between the 2 treatment groups, over time, reaching a maximum at 3 days. We have proposed that these findings represent a temporal separation between fluid removal and dyspnea relief, which may be particularly driven by patients with right heart failure.
Second, our population differs from that described by Shlipak et al. (2), with chronic kidney disease but without heart failure. All patients in our study had heart failure, and although we enriched the population with patients with kidney dysfunction, it is likely that the latter was predominantly due to heart failure. We concur that the pathophysiology of dyspnea is complex, potentially linked to inadequate cardiac output as well as to pulmonary hypertension and ischemic heart disease. Each of these factors was likely present within our population, regardless of kidney function.
Third, we saw no difference in the primary endpoint based on kidney function. Figure 2 in our paper (1) shows no interaction between day-1 dyspnea response to tolvaptan and either estimated glomerular filtration rate or serum creatinine. We stress that this finding does not mean that patients with kidney dysfunction had no response to tolvaptan—only that these patients responded similarly to the rest of the population in failing to manifest a differential dyspnea response during the initial day of treatment.
Finally, we applaud Dr. Abdulhadi and colleagues in highlighting the complexity of the mechanisms responsible for dyspnea. Dyspnea is the most common symptom of patients presenting with heart failure, and work should continue to identify treatments to address the underlying physiology behind this important source of discomfort and disability.
Please note: Dr. Konstam has received research support from Otuska Pharmaceuticals for the conduct of this clinical trial; and honoraria. Dr. Udelson has received research support from Otuska Pharmaceuticals for the conduct of this clinical trial. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. Randall Starling, MD, served as Guest Editor for this paper.
- 2017 American College of Cardiology Foundation