Left ventricular ejection fraction as therapeutic target: is it the ideal marker?

Heart failure (HF) consists the fastest growing clinical cardiac disease. HF patients are categorized on the basis of underlying left ventricular ejection fraction (LVEF) into HF with preserved EF (HFpEF), reduced LVEF (HFrEF), and mid-range LVEF (HFmrEF). While LVEF is the most commonly used surrogate marker of left ventricular (LV) systolic function, the implementation of two-dimensional echocardiography in estimating this parameter imposes certain caveats on current HF classification. Most importantly, LVEF could fluctuate in repeated measurements or even recover after treatment, thus blunting the borders between proposed categories of HF and enabling upward classification of patients. Under this prism, we sought to summarize possible procedures to improve systolic function in patients with HFrEF either naturally or by the means of pharmacologic and non-pharmacologic treatment and devices. Therefore, we reviewed established pharmacotherapy, including beta-blockers, inhibitors of renin-angiotensin-aldosterone axis, statins, and digoxin as well as novel treatments like sacubitril-valsartan, ranolazine, and ivabradine. In addition, we assessed evidence in favor of cardiac resynchronization therapy and exercise training programs. Finally, innovative therapeutic strategies, including stem cells, xanthine oxidase inhibitors, antibiotic regimens, and omega-3 polyunsaturated fatty acids, were also taken into consideration. We concluded that LVEF is subject to changes in HF after intervention and besides the aforementioned HFrEF, HFpEF, and HFmrEF categories, a new entity of HF patients with recovered LVEF should be acknowledged. An improved global and refined LV function assessment by sophisticated imaging modalities and circulating biomarkers is expected to render HF classification more accurate and indicate patients with viable-yet dysfunctional-myocardium and favorable characteristics as the ideal candidates for LVEF recovery by individualized HF therapy.