4. Physicians need to be mindful to protect the right ventricle of patients with HFpEF.
Both pulmonary hypertension and RV dysfunction are highly prevalent in HFpEF. RV dysfunction probably results from a combination of impaired RV contractile function and elevated RV afterload. Longitudinal HFpEF studies have shown that RV structure and function worsen over time; this deterioration has been associated with atrial fibrillation, coronary artery disease, obesity, and increased left heart and pulmonary venous pressures.
As left heart filling pressures rise, the pulmonary vasculature becomes less compliant, increasing RV afterload. In addition, remodeling of the pulmonary vasculature, including intimal thickening in the veins and intimal and medial thickening in the arteries, may occur. Therefore, tailored diuretic therapy to normalize left heart filling pressures and prevent pulmonary congestion is a mainstay of treatment for patients with HFpEF. Discharge diuretics were recently associated with both a reduction in 30-day HF rehospitalizations and mortality in patients with HF, independent of ejection fraction. In the setting of diuretic resistance, transitioning patients from furosemide to a loop diuretic with more consistent bioavailability (eg, bumetanide, torsemide) may also be helpful. Although thiazide diuretics may be used on an as-needed basis to facilitate diuresis, their daily use in conjunction with a loop diuretic should be limited in the outpatient setting owing to the risk for kidney injury and electrolyte abnormalities. Finally, implantable pulmonary artery pressure monitoring devices may be particularly useful in the HFpEF population to maintain and achieve euvolemia, proving effective in guiding diuretic therapy in order to reduce hospitalizations.
Although physiologically tempting, pulmonary vasodilator therapy is currently contraindicated in this population and may only be given to patients in a clinical trial setting. Two such studies, one testing whether sildenafil improves outcomes in patients with persistent pulmonary hypertension and the other evaluating the effects of macitentan on pulmonary hypertension with LV dysfunction, have suggested worse outcomes with these therapies.
5. Patients with refractory HFpEF should consider enrolling in clinical trials.
The lack of effective medical therapies for HFpEF has led researchers to reassess clinical trial designs for HFpEF. In particular, the delineation of specific clinical (eg, HFpEF with right heart failure), hemodynamic (eg, marked rise in left-sided filling pressures with exertion), and genetic (eg, amyloid) phenotypes is now shaping trial enrollment in an attempt to better match drug and device mechanisms to pathophysiologic mechanisms. (HFpEF with concomitant right ventricular failure, HFpEF with predominant exercise intolerance, and HFpEF due to amyloidosis are just some examples of phenotypic variants.) One example includes interatrial shunt devices that produce left-to-right shunts, lowering left atrial pressures (particularly during exertion). Initial studies on such devices have enrolled carefully selected patients with HFpEF whose hemodynamic profiles favor left-to-right shunting. Early results from ongoing major outcome trials, such as REDUCE LAP-HF I, have shown promise.
Physicians caring for patients with refractory HFpEF are strongly encouraged to refer them to a specialized center participating in clinical trials. Such participation may benefit not only these patients but others like them who are seriously in need of therapeutic options.
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