Treatment optimization in heart failure patients from admission to discharge


Department of Heart Diseases
Wroclaw Medical University
Wroclaw, POLAND
Centre for Heart Diseases
4th Military Hospital
Wroclaw, POLAND

Treatment optimization in heart failure patients from admission to discharge

by P. Ponikowski and E. A. Jankowska,

Cardiac decompensation leading to hospital admission is a life-threatening condition, which always requires timely and accurate diagnostic and therapeutic procedures. Due to the clinical heterogeneity of patients with acute heart failure (AHF) and the complexity of underlying pathophysiology, a uniform and simple diagnostic and therapeutic algorithm does not exist. The entire in-hospital stay—from emergency department to hospital discharge—should always be viewed as a continuum, with clearly defined and prioritized therapeutic goals based on careful evaluation of the AHF patient’s clinical status. This paper will discuss the strategies that can be applied at each phase of in-hospital management in order to improve the outcomes of patients with AHF.

Medicographia. 2015;37:149-154 (see French abstract on page 154)

Hospitalization due to circulatory decompensation occurring either as an exacerbation of chronic heart failure (HF) or de novo HF should always be considered to be life threatening, requiring prompt and accurate diagnosis and initiation of adequate therapy.1,2,3 In-hospital management of patients with acute HF (AHF) should be viewed as a “continuum” with consecutive phases (immediate, intermediate, and predischarge phases), each comprising different goals of therapy.

Immediate phase

During the initial (immediate) phase, beginning at admission, typically in the emergency department, major goals of management include4:
(i) clinical stabilization (restoration of peripheral oxygenation and optimal ventilation, restoration of optimal hemodynamics and organ perfusion);
(ii) fast, effective, and sustainable relief of symptoms (most commonly dyspnea);
(iii) elimination of end-organ damage (including myocardium, kidneys, and liver);
(iv) reduction in the risk of early complications; and
(v) shortening of length of stay in intensive care.

Heterogeneity of patients with AHF

Difficulties in the management of HF decompensation are related to the complexity of this syndrome, owing to various, often unidentified, causes that include distinct clinical conditions with heterogeneous and often uncertain pathophysiology and the fact that its clinical course is modified by numerous cardiovascular and noncardiovascular comorbidities. All these factors have significant effects on applied therapeutic strategies. It should be emphasized that there is no uniform and simple diagnostic and therapeutic algorithm for the management of patients with AHF.

Prompt treatment and careful monitoring

All patients admitted with AHF should be promptly treated, and diagnostic procedures should be implemented in parallel with respective treatment.4 Currently, therapeutic decisions are based on the initial presentation, clinical severity, and changes in clinical status, particularly in the initial phase. From the very beginning, monitoring of the patient’s vital functions is essential and many patients should be managed in an intensive or coronary care unit, at least during the initial hours.

Identification of life-threatening conditions

Firstly, the following life-threatening conditions should be identified and, if present, they should be adequately treated immediately:
(i) inadequate ventilation and/or peripheral oxygenation (treatment: oxygen; in more severe cases, noninvasive ventilation, or even endotracheal intubation and invasive ventilation);
(ii) life-threatening tachy- or bradyarrhythmias (treatment: electrical cardioversion or temporary pacing);
(iii) cardiogenic shock or symptomatic hypotension (treatment: inotropic agents and vasopressors; in more severe cases, mechanical circulatory support);
(iv) acute coronary syndrome as a potential cause of hemodynamic deterioration (treatment: coronary arteriography followed by revascularization); and
(v) acute mechanical cause as a potential cause of hemodynamic deterioration (treatment: imaging techniques followed by either surgical or percutaneous interventions).

Management of patients with AHF based on clinical profiles at admission

The clinical presentation of AHF ranges from a gradual worsening of chronic HF (ie, peripheral edema and dyspnea) to life-threatening pulmonary edema or cardiogenic shock. In clinical practice, a simultaneous assessment of congestion and peripheral hypoperfusion allows the identification of 4 different hemodynamic profiles,5,6 which predict outcomes, but most importantly pose several therapeutic consequences:
(i) “wet and warm” (congestion and adequate peripheral perfusion; the most common clinical profile of AHF);
(ii) “wet and cold” (congestion and peripheral hypoperfusion);
(iii) “dry and cold” (no congestion and peripheral hypoperfusion); and
(iv) “dry and warm” (no congestion and adequate peripheral perfusion).

Importantly, there are 2 distinct clinical entities within a “warm and wet” profile, which are triggered by different pathomechanisms and require different therapeutic strategies7,8:
(i) congestion due to fluid accumulation with concomitant weight gain and peripheral edema; typically, rather slow deterioration, gradual (over several days) development of symptoms, and a previous history of chronic HF with systolic dysfunction; treatment should be based on diuretics in order to remove fluid overload; and
(ii) congestion due to fluid redistribution from splanchnic vasculature to the lungs without (or with minimal) weight gain; typically, rapid deterioration (sometimes flash pulmonary edema); treatment should be based on vasodilators, sometimes combined with rather low doses of diuretics.7,8,9

Diuretic strategies

Diuretics are the most frequently used drugs in patients with AHF.10 ESC guidelines recommend intravenous loop diuretics to reduce dyspnea and relieve congestion (class I, level of evidence B).4 Symptoms, urine output, renal function, and electrolytes should be carefully monitored to avoid hypovolemia, renal dysfunction, and hypokalemia.4 The optimal dose and mode of intravenous diuretic administration (bolus or continuous infusion) are uncertain, but in general, high doses may be deleterious. In patients admitted with pulmonary edema/ congestion already taking loop diuretics, an initial dose should be 2.5 times the existing oral dose. In those with insufficient diuretic response, a switch from furosemide to bumetanide or torasemide or a combination of a loop diuretic and a thiazide (eg, bendroflumethiazide) may be considered after a careful assessment of fluid status. In selected cases, venovenous isolated ultrafiltration can be used here. In patients with AHF and cardiorenal syndrome, a standard stepped pharmacologic- therapy algorithm has been shown to be superior to a strategy of ultrafiltration for the preservation of renal function, with a similar effect on weight loss with 2 approaches.11 Importantly, use of ultrafiltration has been associated with a higher rate of adverse events.

Vasodilating strategies

For patients with fluid redistribution and/or high systemic vascular resistance, a combination of vasodilator (the most commonly used are nitrates, but sometimes also nitroprusside or nesiritide) and diuretic should be used to relieve congestion and alleviate symptoms.4 They affect hemodynamics, ie, they reduce both a preload (and pulmonary capillary wedge pressure) and an afterload, and hence may increase cardiac output. Intravenous infusion of a vasodilator is recommended for patients with pulmonary edema/congestion and preserved systolic blood pressure (>110 mm Hg). Nitrate treatment may cause significant hypotension when administered without careful blood pressure monitoring, and a tolerance to prolonged nitrate use may occur. Nitrates should be used with caution in patients with concomitant, clinically relevant aortic or mitral stenosis. A recent study with nesiritide given in the early phase of AHF demonstrated only a modest symptomatic improvement without any impact on outcomes as compared with standard therapy.12

Inotropic and vasopressor strategies

In patients with low blood pressure, signs and symptoms of peripheral hypoperfusion, and low cardiac output, there is usually an indication to initiate inotropic support in order to stabilize compromised hemodynamics and improve peripheral perfusion.4 In clinical practice, therapy usually starts with dobutamine (a β1-adrenergic agonist producing dose-dependent positive inotropic and chronotropic effects), but phosphodiesterase III inhibitors (milrinone, enoximone) and levosimendan (calcium sensitizer improving cardiac contractility by binding to troponin C in cardiomyocytes) are also available. Dopamine is another often used inotropic agent, which stimulates β-adrenergic receptors (when used in moderate doses) and α-adrenergic receptors with subsequent vasoconstriction (when used in larger doses, exceeding 5 μg/kg/min). If a combination of inotropic support and diuretic therapy is not leading to clinical stabilization, adding a vasopressor (mainly dopamine or norepinephrine) may be considered. In the most severe cases, intra-arterial blood pressure monitoring should also be considered; in some centers,pulmonary artery catheterization is applied in order to optimally treat severely compromised hemodynamics, which becomes the main goal of therapy. Another option that may be considered is temporary mechanical support with either an intra-aortic balloon pump or ventricular assist device, particularly if there are potentially reversible causes of acute deterioration (either as a bridge to a final decision or as a bridge to treatment response).

Intermediate and predischarge phases

Once clinical conditions are stabilized and there is symptomatic improvement, a patient is transferred to the ward where the next phases—intermediate and predischarge—are initiated.4,13,14 This period constitutes the initiation of the transition from hospital to ambulatory outpatient setting with relevant implications on the long-term outcomes. From the health care perspective, key recommendations should be initiated here, due to patient receptivity and the opportunity to implement long-term intervention strategies. In this phase, the following goals should be prioritized:
(i) maintenance of patient stabilization with optimized treatment;
(ii) initiation, uptitration, and optimization of disease-modifying pharmacological therapy;
(iii) identification of the underlying HF etiology and relevant comorbidities;
(iv) careful consideration of device therapy in appropriate patients;
(v) optimization of fluid and hemodynamic status (targeting euvolemia);
(vi) predischarge risk stratification in order to identify high-risk patients; and
(vii) enrollment in a disease management program, education (regarding both a patient and relatives), and initiation of appropriate lifestyle adjustments.

Importantly, in addition to timely outlining of all these goals, in each phase of AHF, management should be adjusted to a patient’s clinical profile and the effects of therapy carefully monitored. This strategy may result in further improvement of long-term outcomes.

Management plan

In all patients hospitalized due to AHF, after stabilization and transfer to the ward, a key element of effective management should be a detailed, individualized management plan, which should include the implementation of pharmacological interventions, devices, invasive procedures, and rehabilitation, obviously based on current recommendations.4 Most importantly, all medical professionals taking care of patients with AHF should have in mind that the major goal of applied therapies should not be just a reduction in mortality. Rather, they should make all available efforts to reduce the rate of subsequent HF hospitalizations, along with a reduction in days spent in hospitals, as well as to alleviate HF symptoms and to improve quality of life.

Serial clinical monitoring

An AHF patient transferred to the ward from the intensive care unit still needs careful clinical re-evaluation and monitoring. That should be based on simple, but clinically relevant, serial measures from physical examination, such as blood pressure, heart rate, body weight, severity of HF signs and symptoms (peripheral edema, pulmonary congestion, dyspnea, and jugular venous dilatation), along with basic laboratory tests (renal function, electrolytes). These clinical parameters on the one hand provide important prognostic information, but on the other hand, and most importantly, are crucial for further therapeutic decisions to be taken in patients with recent AHF. Recently, Metra et al15 proposed that predischarge assessment should be based on the comprehensive, but simple, evaluation of the following elements: clinical variables (signs of congestion, blood pressure, heart rate, and orthostatic test), electrocardiogram (duration of the QRS complex, presence of atrial fibrillation), and selected laboratory examinations (natriuretic peptides, renal function, electrolytes, anemia, iron deficiency [ID], and myocardial viability). Among them, elevated heart rate seems to be of particular interest as there is growing evidence that, similarly to chronic HF and also in patients discharged after HF decompensation, it predicts an unfavorable outcome.16,17 In a study of patients hospitalized for HF with a left ventricular ejection fraction ≤40% and who are not in atrial fibrillation/flutter or pacemaker dependent (participants of the EVEREST trial [Efficacy of Vasopressin antagonism in hEart failuRE: outcome Study with Tolvaptan], an increased heart rate ≥70 beats per min (bpm) in both 1- and 4-week postdischarge assessment was associated with increased all-cause mortality (Figure 1).16 In order to reverse this unfavorable phenomenon in such patients, it seems reasonable to consider pharmacological treatment to reduce resting heart rate during the early postdischarge phase using a β-blocker and/or ivabradine.

Figure 1
Figure 1. High resting heart rate during an early postdischarge period (1-week and 4-week) after hospitalization due to acute heart failure
as a predictor of high mortality. Kaplan-Meier curves for all-cause mortality, by heart rate quartile. Log rank P<0.0001. N=1947 patients with heart failure and left ventricular systolic dysfunction in sinus rhythm from the EVEREST study.

Abbreviations: bpm, beats per minute; EVEREST, Efficacy of Vasopressin antagonism in hEart failuRE: outcome Study with Tolvaptan; HR, heart rate; Q, quartile.
After reference 16: Greene et al. JACC Heart Fail. 2013;1:488-496. © 2013, American College of Cardiology Foundation. Published by Elsevier, Inc. All rights reserved.

Optimization of pharmacotherapy

Based on clinical status, diuretic therapy should be optimized (a replacement of intravenous diuretics by oral diuretics, a reduction in daily diuretic dose to a minimal adequate dose, though still targeting euvolemia). At the same time, in patients with systolic HF, life-saving therapies should be carefully implemented. These include angiotensin-converting enzyme (ACE) inhibitors (or angiotensin receptor blockers if ACE inhibitors are not tolerated), β-blockers, and mineralocorticoid receptor antagonists.4 Optimally, a triple combined therapy with these agents needs to be initiated in the hospital (based on clinical status and renal function permitting) and further optimized during the postdischarge period.4

Revascularization and anti-arrhythmic strategies

In patients admitted with AHF, a potential ischemic trigger should always be taken into consideration. For those with co-incidence of AHF with acute coronary syndrome, immediate transfer to a catheterization laboratory with further urgent revascularization should be considered. In all remaining patients, where on the basis of clinical evaluation myocardial ischemia can contribute to HF progression and hemodynamic decompensation, careful diagnostic procedures should be implemented; in the case of proven ischemia, an individualized decision about coronary revascularization with optimal mode and timing should always be discussed among the experts. It is also important to verify the indications for implantation of devices (implantable cardioverter defibrillator [ICD], cardiac resynchronization therapy [CRT]) as well as potential ablations of arrhythmias in patients with recent AHF.

Searching for comorbidities

According to the ESC guidelines, active screening for comorbidities and their optimal treatment is crucial for patients with HF and should constitute an element of a comprehensive assessment also during the intermediate and predischarge phases before the postdecompensation discharge. The presence of certain comorbidities, as well as their number, also contributes to the identification of particularly high-risk patients with recent AHF. Data from the Heart Failure Long- Term Registry demonstrate that the prevalence of most comorbidities is more common in patients hospitalized for worsening HF as compared with those with stable chronic HF (respectively for these 2 groups: atrial fibrillation, 44% vs 38%; diabetes mellitus, 39% vs 32%; chronic obstructive pulmonary disease (COPD), 20% vs 14%; prior stroke/transient ischemic attack (TIA), 13% vs 9%; renal dysfunction, 26% vs 18%; hepatic dysfunction, 8% vs 3%; all P<0.0001).10

Screening for comorbidities would allow identification of certain ones and to optimize their treatment, as well as to modify the standard therapies applied in patients with HF based on concomitant chronic diseases. Also, basic parameters such as ferritin or transferrin saturation, reflecting iron status and recommended by ESC guidelines to be assessed in HF patients, allow diagnosis of ID and identify those who can be effectively supplemented. Of AHF patients, 37% have ID, which unfavorably affects their 12-month survival18 and could constitute a potential therapeutic target.

The prime example of a comorbidity that may affect the applied HF treatment is COPD. COPD, occurring in 20% of patients with recent AHF,10 worsens the prognosis and constitutes an important barrier to optimal β-blocker therapy and to an effective strategy for heart rate lowering (as COPD itself is accompanied by high resting heart rate). Data from the SHIFT trial (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) have shown that the primary composite end point of hospitalization for worsening HF or cardiovascular death, and its component, hospitalization for worsening HF, were more common in patients with COPD.19 β-Blockers were prescribed to 69% of COPD patients and 92% of non-COPD patients. The efficacy and safety profile regarding the ivabradine treatment were similar in patients both with and without COPD,19 hence this therapy could constitute an alternative to β-blockers as a safe and effective heart rate– lowering strategy. Moreover, additional analyses from the SHIFT trial demonstrated that worsening renal function (WRF), a common problem in patients with recent AHF (defined here as a creatinine increase of ≥0.3 mg/dL and ≥25% from the baseline value), was directly proportionally related to baseline heart rate, with an incremental risk of 5% for every 5- bpm heart rate increment.20 WRF increased a risk of the primary composite end point of hospitalization for worsening HF or cardiovascular death and of all-cause mortality, whereas ivabradine therapy was equally safe and effective regarding a reduction in the primary composite end point in patients both with and without WRF.20 Similarly, recent evidence suggests that ivabradine therapy was equally safe and effective regarding a reduction in the primary composite end point in patients both with and without diabetes.21

Plan for postdischarge management

The final (predischarge) stage of management of patients hospitalized due to AHF should comprise the analysis and synthesis of all data that were obtained during the hospitalization, including the clinical course during hospitalization, the applied therapeutic interventions and their effectiveness regarding the improvement in clinical status, and the comprehensive picture of cardiovascular and noncardiovascular status of the patient with its effect on therapeutic decisions. Taken together, this evidence should form the basis for the plan for further diagnostic and therapeutic steps during the postdischarge stage in the management of a patient discharged after circulatory decompensation. A beneficial plan would be the enrollment of a patient in a long-term outpatient disease management program, associated with proper education (regarding both a patient and his/her relatives), and an initiation of appropriate lifestyle adjustments, including a proper diet and exercise programs.

1. Ambrosy AP, Fonarow GC, Butler J, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63:1123-1133.
2. Desai AS, Stevenson LW. Rehospitalization for heart failure: predict or prevent? Circulation. 2012;126:501-506.
3. Mentz RJ, Felker GM, Ahmad T, et al. Learning from recent trials and shaping the future of acute heart failure trials. Am Heart J. 2013;166:629-635.
4. McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787-1847.
5. Nohria A, Tsang SW, Fang JC, et al. Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J Am Coll Cardiol. 2003;41:1797-1804.
6. Stevenson LW. Design of therapy for advanced heart failure. Eur J Heart Fail. 2005;7:323-331.
7. Metra M, Felker GM, Zaca V, Bugatti S, et al. Acute heart failure: multiple clinical profiles and mechanisms require tailored therapy. Int J Cardiol. 2010;144: 175-179.
8. Cotter G, Metra M, Milo-Cotter O, Dittrich HC, Gheorghiade M. Fluid overload in acute heart failure—re-distribution and other mechanisms beyond fluid accumulation. Eur J Heart Fail. 2008;10:165-169.
9. Mentz RJ, Kjeldsen K, Rossi GP, et al. Decongestion in acute heart failure. Eur J Heart Fail. 2014;16:471-482.
10. Maggioni AP, Anker SD, Dahlstrom U, et al; Heart Failure Association of the ESC. Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail. 2013;15: 1173-1184.
11. Bart BA, Goldsmith SR, Lee KL, et al; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367:2296-2304.
12. O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32-43.
13. Basoor A, Doshi NC, Cotant JF, et al. Decreased readmissions and improved quality of care with the use of an inexpensive checklist in heart failure. Congest Heart Fail. 2013;19:200-206.
14. Barnason S, Zimmerman L, Nieveen J, Schulz P, Young L. Patient recovery and transitions after hospitalization for acute cardiac events: an integrative review. J Cardiovasc Nurs. 2012;27:175-191.
15. Metra M, Gheorghiade M, Bonow RO, Dei Cas L. Postdischarge assessment after a heart failure hospitalization: the next step forward. Circulation. 2010;122: 1782-1785.
16. Greene SJ, Vaduganathan M, Wilcox JE, et al; EVEREST Trial Investigators. The prognostic significance of heart rate in patients hospitalized for heart failure with reduced ejection fraction in sinus rhythm: insights from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial. JACC Heart Fail. 2013;1:488-496.
17. Habal MV, Liu PP, Austin PC, et al. Association of heart rate at hospital discharge with mortality and hospitalizations in patients with heart failure. Circ Heart Fail. 2014;7:12-20.
18. Jankowska EA, Kasztura M, Sokolski M, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J. 2014;35:2468-2476.
19. Tavazzi L, Swedberg K, Komajda M, et al; SHIFT Investigators. Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. Int J Cardiol. 2013;170:182-188.
20. Voors AA, van Veldhuisen DJ, Robertson M, et al; SHIFT investigators. The effect of heart rate reduction with ivabradine on renal function in patients with chronic heart failure: an analysis from SHIFT. Eur J Heart Fail. 2014;16:426-434.
21. Komajda M, Tavazzi L, Swedberg K, et al; On behalf of the SHIFT Investigators. Clinical profiles and outcomes of patients with chronic heart failure and diabetes: efficacy and safety of ivabradine. A SHIFT study analysis. Eur J Heart Fail. 2014;16(suppl 2):42. Abstract P227.

Keywords: acute heart failure; management plan; therapy optimization