Definitions of Stage D heart failure and outcomes among outpatients with heart failure and reduced ejection fraction.

BACKGROUND: An operational consensus definition of Stage D heart failure (HF) is currently lacking. METHODS: We evaluated 512 outpatients (median age, 63 years; 35.0% women; 45.5% white and 45.9% black; median ejection fraction was 25%; 67.4% had coronary artery disease) with HF and reduced (≤40%) ejection fraction. We applied 3 hypothetical definitions for Stage D: (1) designation as "Stage D" or "advanced" HF by treating physician; (2) INTERMACS profiles, defining Stage D as profiles 2-6; and (3) European Society of Cardiology Heart Failure Association (ESC-HFA) criteria. RESULTS: Physicians, INTERMACS profiles, and ESC-HFA criteria identified 64 (12.5%), 93 (18.2%), and 67 (13.1%) patients, respectively, as Stage D, with modest concordance between definitions (κ = 0.37). After a median of 3.1 years, 97 patients died (3-year mortality 20.4%). Among patients identified as Stage D by physicians, 3-year mortality was 43.7% vs. 17.0% for non-Stage D patients (age-adjusted hazard ratio [HR] 3.17; 95%CI 1.94-5.18; P < 0.001). The corresponding mortalities for the INTERMACS-based definition were 41.0% vs. 16.2% (HR 3.28; 95%CI 2.11-5.11; P < 0.001) and for ESC-HFA criteria 33.5% vs. 18.6% (HR 2.02; 95%CI 1.22-3.33; P = 0.006); the INTERMACS-based definition provided the best prognostic separation. Results were similar with an alternative INTERMACS-based definition considering only profiles 2-5 as Stage D HF. The INTERMACS-based definition best separated all-cause and HF-specific hospitalization and composite endpoint risk between Stage D and non-Stage D patients also. CONCLUSIONS: INTERMACS profiles provide a practical alternative for the identification of Stage D HF in ambulatory populations with systolic HF. The ESC-HFA criteria offer limited prognostic information.

INTERMACS Profiles and Outcomes Among Non-Inotrope-Dependent Outpatients With Heart Failure and Reduced Ejection Fraction.

OBJECTIVES: This study sought to evaluate INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles for prognostic use among ambulatory non-inotrope-dependent patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Data for INTERMACS profiles and prognoses in ambulatory patients with HFrEF are limited. METHODS: We evaluated 3-year outcomes in 969 non-inotrope-dependent outpatients with HFrEF (EF: ≤40%) not previously receiving advanced HF therapies. Patients meeting an INTERMACS profile at baseline were classified as profile 7 (n = 348 [34.7%]); 146 patients (14.5%) were classified profile 6; and 52 patients (5.2%) were classified profile 4 to 5. Remaining patients were classified "stable Stage C" (n = 423 [42.1%]). RESULTS: Three-year mortality rate was 10.0% among stable Stage C patients compared with 21.8% among INTERMACS profile 7 (hazard ratio [HR] vs. Stage C: 2.45; 95% confidence interval [CI]: 1.64 to 3.66), 26.0% among profile 6 (HR: 3.93; 95% CI: 1.64 to 3.66), and 43.8% among profile 4 to 5 (HR: 6.35; 95% CI: 3.51 to 11.5) patients. Hospitalization rates for HF were 4-fold higher among INTERMACS profile 7 (38 per 100 patient-years; rate ratio [RR] vs. Stage C: 3.88; 95% CI: 2.70 to 5.35), 6-fold higher among profile 6 patients (54 per 100 patient-years; RR: 5.69; 95% CI: 3.72 to 8.71), and 10-fold higher among profile 4 to 5 patients (69 per 100 patient-years; RR: 9.96; 95% CI: 5.15 to 19.3) than stable Stage C patients (11 per 100 patient-years). All-cause hospitalization rates had similar trends. INTERMACS profiles offered better prognostic separation than NYHA functional classifications. CONCLUSIONS: INTERMACS profiles strongly predict subsequent mortality and hospitalization burden in non-inotrope-dependent outpatients with HFrEF. These simple profiles could therefore facilitate and promote advanced HF awareness among clinicians and planning for advanced HF therapies.

Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function.

Arrhythmogenic right ventricular cardiomyopathy, a genetically inherited disease that results in fibrofatty replacement of normal cardiac myocytes, has been associated with sudden cardiac death in athletes. Long-term participation in endurance exercise hastens the development of both the arrhythmic and structural arrhythmogenic right ventricular cardiomyopathy phenotypes. We describe the unusual case of a 34-year-old, symptomatic, female endurance athlete who had arrhythmogenic right ventricular cardiomyopathy in the presence of a structurally normal right ventricle. Clinicians should be aware of this infrequent presentation when evaluating athletic patients who have ventricular arrhythmias and normal findings on cardiac imaging studies.

Progression to Stage D Heart Failure Among Outpatients With Stage C Heart Failure and Reduced Ejection Fraction.

OBJECTIVES: This study sought to estimate the rate of progression to Stage D heart failure (HF) among outpatients with Stage C HF and to identify risk factors for progression. BACKGROUND: The pool of patients who may be candidates for advanced HF therapies is growing. METHODS: We estimated 3-year progression to clinically determined Stage D HF and competing mortality among 964 outpatients with Stage C heart failure with reduced ejection fraction (HFrEF), where ejection fraction is ≤40%. RESULTS: The mean age of patients was 62 ± 15 years; 35% were women; 47% were white; 46% were black, and 7% were of other races; median baseline ejection fraction was 28% (25th to 75th percentile: 20% to 35%); and 47% had ischemic heart disease. After 3.0 years (25th to 75th percentile: 1.7 to 3.2 years), 112 patients progressed to Stage D (3-year incidence: 12.2%; 95% confidence interval [CI]: 10.2% to 14.6%; annualized: 4.5%; 95% CI: 3.8% to 5.5%), and 116 patients died before progression (3-year competing mortality: 12.9%; annualized: 4.7%; 95% CI: 3.9% to 5.6%). By 3 years, 25.1% of patients (95% CI: 22.2% to 28.1%) had either progressed to Stage D or died (annualized: 9.2%; 95% CI: 8.1% to 10.5%). Annualized progression rates were higher in black versus white patients (6.3% vs. 2.7%, respectively; p < 0.001), nonischemic versus ischemic patients (6.1% vs. 2.9%, respectively; p < 0.001), and in New York Heart Association functional class III to IV versus I to II patients (7.5% vs. 1.9%, respectively; p < 0.001) but were similar for men and women (4.7% vs. 4.2%, respectively; p = 0.53). Lower ejection fraction and blood pressure, renal and hepatic dysfunction, and chronic lung disease rates were additional predictors of progression. Predictors of competing mortality were different from those of disease progression. CONCLUSIONS: Among patients with Stage C HFrEF receiving care in a referral center, 4.5% progressed to Stage D HF each year, with earlier progression among black and nonischemic patients. These findings have implications for healthcare planning and resource allocation for these patients.