Repetitive milrinone therapy in ambulatory advanced heart failure patients

Abstract

Background Advanced heart failure (HF) patients usually poorly tolerate guideline‐directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short‐term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up‐titrate GDMT and improve functional class. Hypothesis Repetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients. Methods Advanced HF patients treated with beta‐blockers and implanted with defibrillators were initiated with repetitive, intermittent short‐term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B‐natriuretic peptide (BNP) levels, and echocardiography parameters. Results The cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286−3768] to 631 [278−1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV ( p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change. Conclusions In this small cohort of advanced HF, repetitive, intermittent, short‐term milrinone therapy was found to be safe and potentially efficacious.

Successful conservative management of left ventricular assist device candidates

“…Of note, despite the intermittent use of milrinone in our study and its known limited (2.5 h) half‐life, based on previous publications demonstrating protracted haemodynamic effect following repeated milrinone exposure, 20,21 it is likely that our patients continued to benefit from its haemodynamic effect. Though not currently endorsed by HF guidelines, we recently reported the safety and potential efficacy of intermittent inotropic therapy in advanced HF 22,23 . One may argue that the extended half‐life, attenuated increase in oxygen consumption, and reduced arrhythmogenicity shown with levosimendan 24 might prove it to be the inotrope of choice in this setting.…”

“…Though not currently endorsed by HF guidelines, we recently reported the safety and potential efficacy of intermittent inotropic therapy in advanced HF. 22 , 23 One may argue that the extended half‐life, attenuated increase in oxygen consumption, and reduced arrhythmogenicity shown with levosimendan 24 might prove it to be the inotrope of choice in this setting. Currently, however, most of our experience is with milrinone.…”

Pathophysiology and Management of Heart Failure in the Elderly

“…72 Older adults with advanced HF often poorly respond to the aforementioned guideline-directed medical therapy, and these patients may benefit from repetitive, intermittent, and short-term inotropic (such as milrinone) treatment. 73…”

Clinical implication of ambulatory milrinone therapy in patients with advanced heart failure

“…Laufer‐Perl et al demonstrated that repetitive, intermittent, and short‐term milrinone therapy was safe and potentially efficacious in ambulatory patients with advanced heart failure who were intolerant to maximum GDMT. 1 Several concerns have been raised.…”

“…In their study, participants received IV furosemide and IV iron supplementation if necessary during routine clinic visits concomitantly to milrinone therapy. 1 To exclude their impact on clinical outcomes, we would like to confirm whether these therapies were performed before the milrinone therapy.…”