heart failure

Pharmacological treatment for heart failure with preserved ejection fraction is a complex process. Novel drugs have promising results.


Heart failure (HF) has been considered a common final pathway of many illnesses such as cardiovascular, metabolic, and kidney diseases. Heart failure can be further subcategorized depending on the level of the heart’s ejection fraction – the percentage of blood that leaves the heart during each contraction. The treatment of HF patients with reduced ejection fraction (HFrEF) has progressed, but not for HF patients with preserved ejection fraction (HFpEF). Currently, available trials regarding HFpEF are not able to provide definitive results for appropriate treatments.

American researchers from the Northwestern University Feinberg School of Medicine, therefore, analyzed large-scale multicenter HFpEF clinical trials and discussed the pharmacological efficacy of the available strategies for HFpEF. The pathophysiological mechanism of HFpEF is associated with a pro-inflammatory state that causes coronary microvascular endothelial dysfunction in the heart [e.g., reduced nitric oxide (NO), bioavailability, reduced cyclic GMP (cGMP)/protein kinase G (PKG) signaling, abnormalities in titin, and increased stiffness of cardiomyocytes] and, consequently, leads to HFpEF. A cascade of further events are triggered as a result of HFpEF, including increased left ventricle filling pressures, left atrial dysfunction, atrial fibrillation, pulmonary venous congestion, dyspnea, renal hypoperfusion and dysfunction, water retention, worsened pulmonary venous congestion, pulmonary hypertension, and right ventricular (RV) failure. A neurohormonal modulation is also observed and can explain the efficacy of neurohormonal antagonists as a pharmacological strategy.

Potential benefits may be observed with angiotensin converting enzyme inhibitors, which are widely used in many of the comorbidities commonly associated with HFpEF such as diabetes, hypertension, and chronic kidney disease. HF hospitalizations seem to be reduced using angiotensin-receptor blockers, especially in HF patients with a less severe HFpEF and with lower levels of natriuretic peptides (proteins that induce excessive sodium excretion through urine). A few available studies allow the conclusion that a less severe form of HFpEF and obesity-related HFpEF, as well as patients who are diagnosed with HF syndrome may benefit from mineralocorticoid receptor antagonists. Nitrates do not seem to contribute to the management of HFpEF. Digoxin is also not recommended in most cases of HFpEF, but may have positive effects in HFpEF patients with pulmonary hypertension. Beta-blockers are a very common medication for HFpEF patients; they seem to induce significant improvement in walking distance, but not in oxygen consumption. It is possible that phosphodiesterase type 5 inhibitors may be inefficient in most HFpEF patients, especially in those without severe left ventricular hypertrophy. Novel pharmacological agents that have been tested for the treatment of HFpEF include angiotensin receptor neprilysin inhibitor LCZ696, endothelin receptor antagonists (ERA), inorganic nitrate-nitrite substances, sodium-glucose cotransporter-2 inhibitors (SGLT-2), soluble guanylate cyclase (sGC) stimulators, and riociguat. The potential benefits of these new promising pharmacological strategies are being investigated.

It is unlikely that a single pharmacological agent will be able to provide benefits to every patient in a heterogeneous population living with HFpEF. However, it is possible that target therapies, such as those used in cancer patients, may be potentially efficient for HFpEF syndrome.


Written By: Vagner Raso

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