From the Guidelines
Milrinone should not be used as a primary treatment for patients with HFpEF and decompensated CHF due to severe mitral regurgitation, as its benefits are outweighed by potential risks and the underlying condition is better managed with other therapies. The primary goal in managing these patients is to optimize guideline-directed medical therapy (GDMT) and consider interventions that directly address the mitral regurgitation, such as surgical or transcatheter repair, as suggested by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
For patients with HFpEF and severe mitral regurgitation, the focus should be on symptom management and reducing the severity of mitral regurgitation. Diuretics are the mainstay for symptom management, with careful consideration of preload and afterload reduction. Milrinone, as a phosphodiesterase-3 inhibitor, may actually worsen mitral regurgitation by reducing afterload and increasing regurgitant volume, and its inotropic effects provide minimal benefit in HFpEF where diastolic dysfunction is the primary issue.
Key considerations in managing these patients include:
- Optimizing GDMT to improve secondary mitral regurgitation associated with LV dysfunction, as this can obviate the need for intervention 1.
- Assessing the potential benefit of surgical or transcatheter repair for patients with persistent severe secondary mitral regurgitation despite GDMT, depending on the clinical scenario and patient-centric considerations 1.
- Recognizing that transcatheter edge-to-edge MV repair has been shown to be beneficial in specific patient populations, such as those with persistent symptoms despite GDMT and appropriate anatomy on trans-esophageal echocardiography 1.
If milrinone is considered necessary in the acute setting where other therapies have failed, it should be used with caution, starting at low doses (0.1-0.2 mcg/kg/min without a loading dose), and with careful hemodynamic monitoring due to the risks of arrhythmias, hypotension, and increased myocardial oxygen demand. However, the definitive management of severe mitral regurgitation causing heart failure typically involves surgical or transcatheter valve intervention rather than inotropic support, making milrinone a temporary bridge therapy at best while preparing for more definitive treatment of the underlying valvular disease.
From the Research
Role of Milrinone in HFpEF with Decompensated CHF and Severe Mitral Regurgitation
- There is limited direct evidence on the use of milrinone in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and decompensated Congestive Heart Failure (CHF) due to severe mitral regurgitation 2, 3, 4, 5, 6.
- Milrinone, a phosphodiesterase inhibitor, is typically used in patients with heart failure with reduced ejection fraction (HFrEF) to improve hemodynamic status and reduce symptoms 2.
- In patients with HFpEF, the primary goal of treatment is to manage symptoms and comorbidities, as there are no approved treatments specifically indicated for HFpEF 3, 4, 5, 6.
- The use of milrinone in HFpEF patients with decompensated CHF and severe mitral regurgitation may be considered on a case-by-case basis, but its effectiveness and safety in this population are not well established 2, 3, 4, 5, 6.
Treatment Strategies for HFpEF
- Current treatment strategies for HFpEF focus on managing symptoms and comorbidities, such as hypertension, diabetes, and obesity 3, 4, 5, 6.
- Diuretics may be used to reduce congestion and improve symptoms, but their use should be carefully monitored to avoid dehydration and electrolyte imbalances 4, 5.
- Exercise and lifestyle modifications, such as a healthy diet and regular physical activity, may also be beneficial in improving functional capacity and quality of life in patients with HFpEF 4, 5.
Diagnosis and Pathophysiology of HFpEF
- HFpEF is a complex syndrome characterized by abnormal systolic and diastolic function, left atrial enlargement, pulmonary hypertension, and right ventricular dysfunction 6.
- Diagnosis relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise 6.
- The pathophysiology of HFpEF involves abnormalities in titin and its phosphorylation, increased interstitial fibrosis, and a systemic inflammatory state, which contribute to increased chamber stiffness and reduced myocardial cyclic guanosine monophosphate 6.