Decongestion in acute heart failure

Abstract

Congestion is a major reason for hospitalization in acute heart failure (HF). Therapeutic strategies to manage congestion include diuretics, vasodilators, ultrafiltration, vasopressin antagonists, mineralocorticoid receptor antagonists, and potentially also novel therapies such as gut sequesterants and serelaxin. Uncertainty exists with respect to the appropriate decongestion strategy for an individual patient. In this review, we summarize the benefit and risk profiles for these decongestion strategies and provide guidance on selecting an appropriate approach for different patients. An evidence-based initial approach to congestion management involves high-dose i.v. diuretics with addition of vasodilators for dyspnoea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade with thiazide diuretics or natriuretic doses of mineralocorticoid receptor antagonists. Vasopressin antagonists may improve aquaresis and relieve dyspnoea. If diuretic strategies are unsuccessful, then ultrafiltration may be considered. Ultrafiltration should be used with caution in the setting of worsening renal function. This review is based on discussions among scientists, clinical trialists, and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from 30 November to 1 December 2012.

Keywords: Acute heart failure; Decongestion; Outcomes; Strategies; Volume overload.

Figure 1

Pathophysiology of congestion Abbreviations: RV=right ventricular, RA=right atrial, PA=pulmonary artery, PCWP=pulmonary capillary wedge pressure; LA, left atrial, LV=left ventricular, LVDP=left ventricular diastolic pressure, JVD=jugular venous distension. Reproduced with permission from Gheorghiade M et al, Eur J Heart Fail 2010(13).

Figure 2

The underlying pathophysiological mechanisms of volume overload in acutely decompensated heart failure AVP, arginine vasopressin; GFR, glomerular filtration rate; NO, nitric oxide; RAAS, renin–angiotensin–aldosterone system; ROS, reactive oxygen species; SNS, sympathetic nervous system. Reproduced with permission from Koniari K et al. Eur Heart J Acute Cardiovasc Care, 2013(17).

Figure 3

Diuretic Mechanisms. Proposed positive and negative effects of loop diuretics as well as sites of action for thiazide diuretics and natriuretic doses of aldosterone antagonists. CHF=congestive heart failure; LV=left ventricular; MR=mitral regurgitation; RAAS=renin-angiotensin-aldosterone system. Reproduced, with permission, from Felker GM and Mentz RJ. J Am Coll Cardiol, 2012(39).

Figure 4

Freedom From Heart Failure Rehospitalization. Kaplan-Meier estimate of freedom from rehospitalization for heart failure within 90 days after discharge in the ultrafiltration (red line) and standard care (blue line) groups. Reprinted, with permission, Costanzo et al. J Am Coll Cardiol 2007(69).

Figure 5

Improvement in patient-assessed dyspnea with tolvaptan compared to placebo in EVEREST as a function of time from first dose of study drug. Reproduced with permission from Pang et al. Eur Heart J 2009(74).

Figure 6

An approach to managing congestion in acute HF patients. Abbreviations: IV=intravenous, HF=heart failure, SBP=systolic blood pressure, MRA=mineralocorticoid receptor antagonist.