Current management and future directions for the treatment of patients hospitalized for heart failure with low blood pressure

Abstract

Although patients hospitalized with heart failure have relatively low in-hospital mortality, the post-discharge rehospitalization and mortality rates remain high despite advances in treatment. Most patients admitted for heart failure have normal or high blood pressure, but 15-25 % have low systolic blood pressure with or without signs and/or symptoms of hypoperfusion. All pharmacological agents known to improve the prognosis of patients with heart failure also reduce blood pressure, and this limits their use in patients with heart failure and low blood pressure (HF-LBP). However, patients with HF-LBP have much higher in-hospital and post-discharge mortality. In these patients, a conceptually important therapeutic target is to improve cardiac output in order to alleviate signs of hypoperfusion. Accordingly, the majority of these patients will require an inotrope as cardiac dysfunction is the cause of their low cardiac output. However, the short-term use of currently available inotropes has been associated with further decreases in blood pressure and increases in heart rate, myocardial oxygen consumption and arrhythmias. Agents that improve cardiac contractility without this undesirable effects should be developed. To the best of our knowledge, the epidemiology, pathophysiology and therapy of patients with HF-LBP have not been addressed thoroughly. In June 2010, a workshop that included scientists and clinicians was held in Rome, Italy. The objectives of this meeting were to (1) develop a working definition for HF-LBP, (2) describe its clinical characteristics and pathophysiology, (3) review current therapies and their limitations, (4) discuss novel agents in development and (5) create a framework for the design and conduct of future clinical trials.

Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure, Cardiac Index, and Etiology

“…Following the analysis scheme of the main ESCAPE study, we initially calculated this endpoint with patients receiving transplant or assist devices coded as dead; then we coded these events as alive in a sensitivity analysis. The association between admission SBP, inotropes use, and outcomes was assessed by categorizing SBP into <100 vs. ≥100 mmHg based on previous literature 9, 10 and also by modeling SBP as a continuous variable. We followed a similar approach for cardiac index, using 1.8 L/min/m 2 for categorical analysis.…”

“…8 This discrepant trend is partially rooted in the limited options for management of advanced systolic HF. 9 However, it is also rooted in the belief that inotropes may be beneficial when systolic blood pressure (SBP) is relatively low even without clinical hypoperfusion, 10 or that benefits may outweigh risks in those patients who are in a low cardiac output state, since previous trials were conducted among hospitalized patients without the specific knowledge of central hemodynamics. 5 There are no data however to support these notions.…”

Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

“…MSC therapy did not reverse hypotension. Hypotension in MI could be related to lower cardiac output [36]. The LVEF was reduced in CHF rats despite the MSC treatment.…”

Pulmonary Oedema—Therapeutic Targets

“…These agents have been associated with adverse events such as ischemia, tachyarrhythmias, and hypotension, and may increase in-hospital and postdischarge mortality. 63,64 However, as systemic hypoperfusion in the setting of low CO occurs, sympathomimetic agents remain a mainstay of therapy, despite their associated long-term adverse events, probably mediated through worsening myocardial injury. For sympathomimetic agents, previous treatment with beta-blockers may greatly influence the anticipated clinical response.…”

“…67 These effects are not attenuated by concomitant treatment with beta-blockers and are sustained beyond the duration of the drug infusion because levosimendan has an active metabolite with a long half-life. 1,63,64,66,67 Levosimendan demonstrated a favorable haemodynamic profile in preclinical and clinical studies 63 as it reduced PCWP and increased CO, suggesting potential benefit for patients with PO with low or normal SBP. However, when tested in rigorous randomized double-blind trials, 68,69 levosimendan showed only modest clinical improvement, and was associated with hypotension, atrial and ventricular arrhythmias, and, in one trial, a trend toward an increase in early mortality.…”