Clinical ResearchSERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction
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Section snippets
Study recruitment
As previously described,9 patients with HFpEF were recruited from a university cardiology clinic (University of Texas Southwestern Medical Center, Dallas, Texas, USA). Patients were invited to participate if they were >60 years of age, had undergone hospitalization for HF, had evidence of congestion by either chest radiograph or elevated filling pressures (resting PCWP or LV end-diastolic pressures >16 mm Hg), and had an LV ejection fraction >50%. N-terminal pro–B-type natriuretic peptide
Demographics
Demographic data for HFpEF and senior control subjects are shown in Table 1. A total of 15 patients with HFpEF were enrolled; however, 2 were excluded. One patient with a history of paroxysmal atrial fibrillation developed atrial fibrillation shortly after the right-sided heart catheter was placed, and it reverted to sinus rhythm after the catheter was removed. A second patient was deemed not to have HFpEF on the basis of very low cardiac filling pressures during exercise. Otherwise, there were
Discussion
This study tested the effect of SERCA2a stimulation in facilitating ventricular relaxation and reducing PCWP rise during exercise in patients with HFpEF by using istaroxime, a novel SERCA2a agonist. The primary finding was that istaroxime, infused at a rate 0.5 μg/kg/min, had no meaningful effect on PCWP or markers of relaxation (e′, IVRT) at rest or exercise. An exploratory aim using a higher dose of 1.0 μg/kg/min had a small effect on end-expiratory PCWP reduction of 2 mm Hg during exercise,
Conclusions
Istaroxime, when given at a dose of 0.5 μg/kg/min, had no effect on cardiac filling pressure or parameters of relaxation in patients with HFpEF during submaximal exercise. A higher dose of 1.0 μg/kg/min had no effect on diastolic relaxation across conditions but did lead to a nominal decrease in PCWP of 2.2 mm Hg during exercise compared with saline placebo infusion. The effectiveness of istaroxime on PCWP reduction was inversely correlated with BMI. Future studies using a higher dose
Funding Support and Author Disclosures
This project was supported by the National Institutes of Health (grant RO1 AG17479). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors would like to thank CVie Therapeutics for providing istaroxime.
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