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Circulation. 2022;145:e895–e1032. DOI: 10.1161/CIR.0000000000001063 May 3, 2022 e955 CLINICAL STATEMENTS AND GUIDELINES

versus warfarin has not been studied in patients with ATTR, nor has the role of left atrial appendage closure devices. The risk of anticoagulation on bleeding risk in patients with ATTR-CM and AF has not been established. However, although patients with AL amyloidosis may have acquired hemostatic abnormalities, including coagulation factor deficiencies, hyperfibrinolysis, and platelet dysfunction, TTR amyloidosis is not associated with hemostatic defects.

8 STAGE D (ADVANCED) HF

8.1 Specialty Referral for Advanced HF

Recommendation for Specialty Referral for Advanced HF

COR LOE Recommendation

1 C-LD 1.	 In patients with advanced HF, when consistent with the patient’s goals of care, timely referral for HF specialty care is recommended to review HF management and assess suitability for advanced HF therapies (eg, LVAD, cardiac transplantation, palliative care, and palliative inotropes).1–6

Synopsis A subset of patients with chronic HF will continue to progress and develop persistently severe symptoms despite maximum GDMT. Several terms have been used to describe this population, including “end-stage,” “advanced,” and “refractory” HF. In 2018, the European Society of Cardiology updated its definition of advanced HF (Table 16), which now includes 4 distinct criteria.1 The revised definition focuses on refractory symptoms rather than cardiac function and more clearly acknowledges that advanced HF can occur in patients without severely reduced EF, including those with isolated RV dysfunction, uncorrectable valvular or congenital heart disease, and in patients with preserved and mildly reduced EF.1,3 The INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) has developed 7 profiles that further stratify patients with advanced HF (Table 17).7

Determining that HF and not a concomitant pulmonary disorder is the basis of dyspnea is important. Severely symptomatic patients presenting with a new diagnosis of HF can often improve substantially if they are initially stabilized. Patients should also be evaluated for nonadherence to medications.8–11 Finally, a careful review of medical management should be conducted to verify that all therapies likely to improve clinical status have been considered.

Recommendation-Specific Supportive Text

1.	 Clinical indicators of advanced HF that should trigger possible referral to an advanced HF specialist are shown in Table 18.1,2,12–14 Timely referral for review and consideration of advanced HF therapies is crucial to achieve optimal patient outcomes.15–17 Acronyms such as I-Need-Help... I,  Intravenous inotropes N,  New York Heart Association (NYHA) class IIIB

to IV or persistently elevated natriuretic peptides E,   End-organ dysfunction E,   EF ≤35% D,  Defibrillator shocks H,  Hospitalizations >1 E,   Edema despite escalating diuretics L,   Low systolic BP ≤90, high heart rate P,   Prognostic medication; progressive intolerance or down-titration of GDMT ...have been developed to assist in decision-making for referral to advanced HF.18 Indications and contraindications to durable mechanical support are listed in Table 19. After patients develop end-organ dysfunction or cardiogenic shock, they may no longer qualify for advanced therapies.19,20 A complete assessment of the patient is not required before referral, because comprehensive, multidisciplinary assessment of cardiac disease and comorbid conditions is routinely performed when evaluating patients for advanced therapies.19,20 Decisions around evaluation and use of advanced therapies should be informed by the patient’s values, goals, and preferences. Discussion with

Table 16.  ESC Definition of Advanced HF All these criteria must be present despite optimal guideline-directed treatment:

1 Severe and persistent symptoms of HF (NYHA class III [advanced] or IV)

2.	 Severe cardiac dysfunction defined by ≥1 of these: LVEF ≤30% Isolated RV failure Nonoperable severe valve abnormalities Nonoperable severe congenital heart disease EF ≥40%, elevated natriuretic peptide levels and evidence of significant

diastolic dysfunction 3.	 Hospitalizations or unplanned visits in the past 12 mo for episodes of: Congestion requiring high-dose intravenous diuretics or diuretic com-

binations Low output requiring inotropes or vasoactive medications Malignant arrhythmias 4.	 Severe impairment of exercise capacity with inability to exercise or low 6-minute walk test distance (<300 m) or peak VO2 (<12–14 mL/kg/min) estimated to be of cardiac origin Criteria 1 and 4 can be met in patients with cardiac dysfunction (as described in criterion 2) but who also have substantial limitations as a result of other conditions (eg, severe pulmonary disease, noncardiac cirrhosis, renal disease). The therapeutic options for these patients may be more limited. EF indicates ejection fraction; ESC, European Society of Cardiology; HF, heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; RV, right ventricular; and VO2, oxygen consumption/oxygen uptake.

Adapted with permission from Crespo-Leiro et al.1

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