The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure trial (OPTIME-CHF), randomized 951 patients with AHFS to receive either intravenous milrinone or placebo within 48 hours of hospitalization.18 Compared to placebo, milrinone was associated with a significant increase in sustained hypotension requiring intervention (10.7% vs. 3.2%; p<.001) and new atrial arrhythmias (4.6% vs. 1.5%; p=0.004), along with a non-significant trend toward increased mortality (3.8% vs. 2.3%; p=0.19). However, as measured by a visual analog scale, milrinone-treated patients reported feeling better than those treated with placebo at 30 days post-randomization (p=0.02).
Although there are not randomized data comparing the efficacy of milrinone and dobutamine in AHFS, a retrospective analysis of 329 patients compared the hemodynamic and clinical effects of these two inotropes.19 Milrinone consistently was associated with a more favorable hemodynamic response, including lower systemic vascular resistance (p=0.01); lower pulmonary artery wedge pressure (p<0.001); larger percentage increase in cardiac index (p=0.03); and larger percentage decrease in pulmonary vascular resistance (p=0.0001). In-hospital mortality (dobutamine 7.8% vs. milrinone 10%) was not significantly different.
Conclusion
Clearly, vasoactive and inotropic agents are available when AHFS is refractory to traditional diuresis and may offer short-term symptomatic relief, palliation in the context of end-of-life care, or bridge to recovery or more definitive treatment. Unfortunately, sufficient and robust evidence that supports the safety and efficacy of such agents is lacking and their use is largely guided by historical practices, clinical experience, and anticipation of theoretic physiologic changes. While adequately powered prospective randomized data emerge, newer agents such as vasopressin receptor antagonists, cardiac myosin activators, calcium sensitizers, and adenosine-receptor antagonists will offer additional pharmacologic options.20 When continued pharmacologic support becomes ineffective, device therapy is available to aid in the treatment of AHFS and includes ultrafiltration to reduce filling pressures and intra-aortic balloon pump counterpulsation or left ventricular assist device placement for pharmacologically resistant cardiogenic shock.21
Back to the Case
Despite maximal medical therapy for her chronic heart failure and biventricular pacing, the patient continued to have markedly limited functional status and repeated hospitalizations for AHFS. Given her advanced age and poor nutritional status, she was not a candidate for cardiac transplantation or placement of a left ventricular assist device. To allow for palliative tailored therapy, right heart catheterization was performed. Right heart catheterization revealed elevated filling pressures, as follows: right atrium, 20 mmHg; pulmonary artery, 63/34 mmHg (mean 47 mmHg); and pulmonary capillary wedge, 29 mmHg. Her mixed venous oxygen saturation was only 41% with a calculated cardiac output of 2.9 liters per minute and cardiac index of 2 liters per minute per meter squared.
As she expressed symptomatic relief as her goal, she was started on intravenous milrinone at 0.2 micrograms per kilogram per minute. This was done with the understanding her symptoms would likely would improve, at the expense of worsening longevity and prognosis. With uptitration of her intravenous milrinone and a continuous infusion of furosemide, she demonstrated the following filling pressures within 24 hours: right atrium, 18 mmHg; pulmonary artery, 63/33 mmHg (mean 43 mmHg); and pulmonary capillary wedge, 24. Importantly, her mixed venous oxygen saturation improved to 68% with a calculated cardiac output of 3.4 liters per minute and cardiac index of 2.4 liters per minute per meter squared. These favorable hemodynamic changes were accompanied by modest improvement in symptoms. After continued intravenous diuresis, she was transitioned back to an oral diuretic regimen and was ultimately discharged to home with a continuous infusion of milrinone for palliation. TH
Drs. Vaishnava, McKean, Nohria, and Baughman are from Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass.