Nitrates as a Treatment of Acute Heart Failure

Abstract

Acute heart failure (AHF) presents symptoms primarily the result of pulmonary congestion due to elevated left ventricular (LV) filling pressures with or without reduced ejection fraction (EF). Common precipitating pathology includes coronary artery disease (CAD), hypertension and valvular heart diseases, in addition to other noncardiac conditions, such as diabetes, anaemia and kidney dysfunction. 1,2Additionally, AHF poses major medical and socioeconomic burdens.It represents the most common discharge diagnosis in patients over 65 years of age in the US, and an AHF patient that requires hospitalisation has a 90-day mortality approaching 10 %. 3,4 The cornerstone of AHF treatment is diuretics and vasodilators, such as nitrates. Due to a lack of randomised controlled trials, the use of nitrates for management of AHF is not universally adopted.While organic nitrates are among the oldest treatments for chronic stable angina, they are underutilised in AHF. Organic nitrates are available as sublingual tablets, capsules, sprays, patches, ointments or intravenous (IV) solutions, all of which are potent vasodilators.Because of the challenges in AHF research, a data imbalance between acute and chronic HF treatment exists as more studies have been performed in the latter. Thus, the current level of evidence for the use of nitrates in AHF is only rated as 1C, i.e., 'expert opinion'. 5,6 The purpose of this article is to review the clinical efficacy and safety data of nitrates in AHF. Applied to the patient with congestive HF, vasodilatation induces a substantial reduction in biventricular filling pressure. Moreover, it reduces systemic and pulmonary vascular resistance and systemic arterial blood pressure (BP), 11 all of which lead to modest increases in cardiac stroke volume and cardiac output. How Nitrate Works Mechanism of Action 12Overall, the two most commonly used IV NO sources used clinically in the setting of AHF is the organic nitrate donor nitroglycerin, and the inorganic nitrate source sodium nitroprusside (SNP). Nitroglycerin potently dilates large arteries (including coronary arteries) but has less effect on smaller arterioles, while SNP is a predominant arteriolar dilator. That makes SNP is effective in recompensating patients with AHF. 13 Other important clinical differences between organic and inorganic nitrates are summarised in Table 1. AbstractThe purpose of this article is to review the clinical efficacy and safety of nitrates in acute heart failure (AHF) by examining various trials on nitrates in AHF. Management of AHF can be challenging due to the lack of objective clinical evidence guiding optimal management.There have been many articles suggesting that, despite a benefit, nitrates are underused in clinical practice. Nitrates, when appropriately dosed, have a favourable effect on symptoms, blood pressure, intubation rates, mortality and other parameters.

Evaluation of the effect of intravenous nitroglycerine on short-term survival of patients with acute heart failure according to congestion and perfusion status at emergency department arrival

“…Our subgroups analyses extensively failed in detecting any clinical setting with a more favourable setting for IV-NTG use in patients with AHF. Despite many authors have suggested that prompt initiation of IV-NTG in patients with severe pulmonary congestion (presenting in the form of acute pulmonary oedema) could be beneficial especially if it is quickly provided in the prehospital arena [8,[23][24][25], our subgroup analysis considering signs/symptoms of congestion separately according to whether they correspond to pulmonary or systemic congestion did not support this hypothesis, at least with respect to an improvement in patient survival. Similarly, age, sex, CAD as comorbidity and SBP did not have a different impact on the effects of NTG on patient survival.…”

A novel soluble guanylate cyclase activator with reduced risk of hypotension by short‐acting vasodilation

“…However, the improper use of diuretics causes renal dysfunction and electrolyte abnormalities during clinical acute heart failure . In recent years, the contribution of congestion due to a redistribution of circulating blood has been shown to contribute to clinical pulmonary edema, and initial treatment using a vasodilator is recommended for cases of adaptation . In clinical heart failure, vascular endothelial dysfunction is often seen, and the bioavailability of NO is decreased .…”

“…35,36 In recent years, the contribution of congestion due to a redistribution of circulating blood has been shown to contribute to clinical pulmonary edema, and initial treatment using a vasodilator is recommended for cases of adaptation. 37,38 In clinical heart failure, vascular endothelial dysfunction is often seen, and the bioavailability of NO is decreased. 39,40 Use of a sGC activator, which is an endothelial-functionimproving agent that is independent of NO, is considered reasonable in treating ADHF, if hypotension can be avoided by appropriate use.…”

Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease

“…Intravenous nitroglycerin is also commonly used in acute heart failure to provide rapid dyspnea relief. Relevant mechanisms of nitroglycerin in acute heart failure include reducing myocardial strain, and hemodynamic benefits resulting in decreased right ventricular and left ventricular filling pressures (Alzahri et al, 2016). By enhancing effects of NOmediated signaling, an sGC stimulator might also be expected to favorably affect the heart.…”