Definition and characteristics of the vulnerable phase in heart failure

Cumhuriyet University
Faculty of Medicine
Department of Cardiology

Alexandre MEBAZAA
University Paris Diderot
Hôpital Lariboisière
Paris, FrAnCE

Definition and characteristics of the vulnerable phase in heart failure

by M. B. Yilmaz and A. Mebazaa,
Turkey and France

Heart failure (HF) is a disease with high morbidity and mortality in the long run. Its course is not linear in nature, but characterized by spikes and nadirs with a changing risk profile. It also includes a period called the “vulnerable phase,” during which the patient is at an increased risk for adverse outcomes. Here, vulnerability means that HF patients might experience unexpected outcomes, which could bring about windows of opportunity if addressed properly. This vulnerability is typically observed during the periacute HF period, which extends from initiation of an index acute HF event leading to admission, through a peridischarge period and up to 6 months after discharge. This vulnerable phase could potentially be divided into 3 overlapping phases. Of note, this relatively long-lasting phase is not based solely on a single pathophysiological mechanism, because HF is a complex syndrome. Hence, an individual, but collaborative, approach is required. Whatever the driving mechanisms, tailoring of an individualized therapy by a multidisciplinary team might provide patients with better outcomes and see them through to a stable phase of HF.

Medicographia. 2015;37:144-148 (see French abstract on page 148)

Heart failure (HF) is a complex clinical syndrome. Acute HF (AHF) represents a serious health problem with significant mortality and morbidity in-hospital despite contemporary therapy.1 Although survival of patients with chronic HF has improved over time, postdischarge outcomes of patients with AHF remain unacceptably high. About half the patients with HF are readmitted within 1 year of discharge and about 20% die in the following year, though geographical variations exist.2

The vulnerable phase of HF

The “vulnerable phase,” as typically defined for patients with AHF, is a period during which microenvironmental changes in the cardiovascular milieu after an episode of AHF impose an increased risk for adverse cardiovascular events, including increased risk of death or rehospitalization for HF. Patients who overcome this period successfully may transition into long-term stability. Of note, the vulnerable phase exists whether or not the index attack is the first event. It can theoretically occur with every episode of AHF.

Although the vulnerable phase of HF following an extensive myocardial infarction is a relatively well-established clinical phenomenon, it has recently been noticed to occur with each AHF episode, though the individual impact varies. An episode of AHF is by nature a period of vulnerability. However, physicians can triage the patients according to disease severity and manage them accordingly, though referral to an intensive care unit (ICU)/critical care unit (CCU) itself means increased vulnerability.1 On the other hand, after an AHF episode, patients enter a vulnerable phase that can lead to repeated hospitalizations within a short period. This vulnerable phase requires accurate identification and management strategies.

Figure 1
Figure 1. The vulnerable phase of heart failure.

Abbreviations: AHF, acute heart failure; WHF, worsening heartfailure.

With regard to risk prediction after discharge, several attempts to predict rehospitalization have been described in the literature. Most of these models performed poorly, though some of them may work in individual patients.3 The problem of poor performance might be related to the multidimensional nature of postdischarge management.

Typically, postdischarge adverse events peak up to 2 months after discharge, and then gradually decrease until reaching a plateau around month 6 of the postdischarge period. The plateau may last as long as a year, and then deteriorations may occur.4 Hence, the vulnerable phase of AHF could be considered to comprise 3 overlapping subphases (Figure 1): a very early phase, an early phase, and a late phase.

Very early vulnerable phase
The very early vulnerable phase is subdivided into further overlapping periods and so could be regarded as a heterogeneous period. It extends from an index episode of AHF up to a few days post discharge. As an episode of AHF itself is a vulnerable period, anyone experiencing one is subject to this vulnerability, which is characterized by increased risk of morbidity and mortality.1 Following an initial stabilization of an AHF episode, some patients, potentially up to 15% of the overall population, might experience worsening in HF symptoms and signs that require extra interventions.56 In-hospital worsening of HF has been shown to be associated with an increased risk for adverse outcomes.7

The very early vulnerable phase is typically expected in patients discharged before complete relief of congestion. The mean duration of hospitalization in the United States is 4-5 days.8 In many cases, this is too short for complete stabilization of the AHF patients. Overall, system-induced pressure encourages physicians to discharge patients as early as possible, which leads to the common practice in the United States (unlike many European countries) of using higher doses of diuretics within a short period of time to achieve decongestion.

High-dose diuretics might provide more rapid relief of symptoms and congestion, but at a slightly increased cost of renal impairment,9 and many patients would potentially remain relatively congested following such a discharge. Due to results of the rapidly changing tissue microenvironment, such as an electrolyte disturbance in the form of hypokalemia, tissue ischemia in the form of organ dysfunction may be overlooked at this stage. Of note, organ dysfunction, possibly in the form of renal or hepatic dysfunction, could determine the prognosis of these patients in the very early vulnerable phase.10 Furthermore, anemia at admission might contribute to poor outcomes in this phase if left untreated.

Long-term oral disease-modifying therapies are not easy to initiate within a short hospitalization period. Therefore, patients might experience increased risk of rehospitalization or fatality after discharge simply due to lack of administration of these therapies. These patients require meticulous follow- up by a multidisciplinary team, with short intervals as suggested by guidelines.11 The most recent American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines recommend early telephone follow-up within 3 days of discharge and an early follow-up visit within 2 weeks.

Early vulnerable phase
The early vulnerable phase typically begins after the discharge of a relatively well-decongested patient following an episode of AHF. Hospitalization duration is typically 8-10 days in many European countries.12 That is usually a sufficient period for adequate decongestion and then stabilization of fluid balance (dry weight). However, that might not be long enough for adequate control of accompanying problems. Predischarge, when possible, specialist HF nurses should be involved in educating the patient for nonpharmacological self-management of HF and for adjustment of diuretics in the outpatient setting. This would be helpful, as many of these patients require outpatient management of diuretics for some time. Early referral for cardiac rehabilitation should also be considered. These 2 factors—management of diuretics and cardiac rehabilitation— are important determinants of stability after AHF.

This phase of vulnerability is potentially secondary to a patient’s attitude, ie, restricting lifestyle modifications to the “honeymoon period” following discharge. However, most of the vulnerability is thought to be related to existing problems, ie, comorbidities. As many AHF patients also suffer from renal problems, anemia, hypertension, coronary artery disease, diabetes mellitus, or chronic obstructive pulmonary disease (though a cardiac problem could be relieved to an acceptable level), it is possible that accompanying problems will be uncovered with an index AHF event. These accompanying problems, which typically increase with age, might hold the patient in a period of risk beyond discharge. Therefore, each of the accompanying diseases is a potentially exacerbating factor and might require focused care unless well controlled. Patients with ischemic HF have been shown to be significantly more likely to experience repeated hospital admissions,13 and this theoretically means that repeated episodes of ischemia might be an important contributor to vulnerability. Elevated levels of biomarkers before discharge, such as natriuretic peptides and cardiac troponins, could potentially predict readmission risk. Hence, management during the vulnerable phase could be guided by biomarkers, though that remains to be firmly established.

Thirty percent of all readmissions occur within the first 2 months of hospital discharge.13 Furthermore, cardiovascular events are clustered before fatality.13 With a comprehensive plan and collaborative work, many of these events are preventable. Furthermore, overcoming the problem of systemic congestion does not mean relief of hemodynamic congestion in parallel. Patients in this phase might still require relatively higher doses of diuretics and vasoactive medications. They also require more careful and intimate follow-up. However, it has been shown that less than 50% of patients with HF with reduced ejection fraction (HFrEF) are prescribed guideline- recommended therapies at discharge.14

Typically, β-blockers are recommended for most patients with chronic HF, although such therapy may be discontinued or reduced during hospitalizations. Long-term oral disease-modifying HF therapy should be continued on admission with AHF, except in the case of hemodynamic instability. It has been shown in severe, acutely decompensated HF patients that continuing the existing β-blocker therapy yields the best prognosis, while the worst belongs to those not prescribed β-blockers at discharge though they had been on long-term β-blocker therapy at admission.15 It has been demonstrated that such discontinuation is not needed in patients with AHF except in the case of cardiogenic shock.16 If heart rate remains elevated despite β-blockade in patients with HF, the addition of ivabradine would be beneficial.17 Additionally, in tachycardic AHF patients (in sinus rhythm) who cannot tolerate β-blockers, ivabradine remains an attractive option, though further studies are needed for this indication.18

Prescription rates for these agents, namely, angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and mineralocorticoid receptor antagonists (MrAs), were all higher when patients were admitted to cardiology wards or seen by HF specialists. Furthermore, patients with HFrEF who were discharged along with a prescription for these drugs have significantly better outcomes than those discharged without.14 notably, there is significant heterogeneity in the organization of HF management.19 Transition from inpatient to outpatient care can be very difficult in the vulnerable period due to the complexity of the progressive nature of the disease state itself, accompanying diseases and associated long-term medications, as well as the patient’s perception of the disease. Hence, collaborative care accounting for all variables is needed at every phase. readmission rates for HF in younger adults are similar to those in elderly patients. Thus, a generalized risk after hospitalization is present regardless of age.20 Therefore, patients in this phase require closer clinical follow-up, typically within 1-2 weeks after discharge. Of note, a considerably high percentage of HF readmissions occur before the first scheduled ambulatory visit.21

Late phase
The late phase typically extends up to 6 months. It is related to reactivation of the renin-angiotensin-aldosterone axis and the beginning of hemodynamic congestion before overt systemic congestion. Whatever the medical practice habits in different geographical areas, the overall prognosis of patients from different continents is similar in this phase. Independent of ejection fraction, HF-related rehospitalizations are typically preceded by a gradual rise in ventricular filling pressures more than 2 weeks before the appearance of the overt clin ical picture.22 Hence, a forthcoming episode should be thoroughly investigated according to symptoms and clinical signs, and using any existing modalities, including biomarkers. As AHF is mainly a condition of “congestion,”23 the accurate identification of signs of hemodynamic congestion is critical to the eventual prognosis of the patient.

Poor prognosis in the late phase could be prevented through fine-tuning (uptitration) of ACE inhibitors (or angiotensin receptor blockers), ébeta;-blockers, MrAs, and ivabradine. At this stage, medication adherence is also important to prognosis. Medication adherence should be achieved along with social support.24 Up to this late phase, adverse events decrease relatively over time and then reach a plateau, which could last several months. During this plateau, optimization of diseasemodifying therapies, including device therapy should be the main target.


A vulnerable phase lasting up to 6 months following an episode of AHF exists and is a critical determinant of prognosis. In order to avoid the poor outcomes related to this vulnerable phase, patients should be discharged when they are hemodynamically stable for at least 24-48 hours, euvolemic, and managed on long-term oral medication, and when they have stable organ function, including the kidney and liver. It appears that the best management of the vulnerable phase requires a collaborative and multistep approach.

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Keywords: acute heart failure; outcome; peridischarge; postdischarge; vulnerable phase