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Defining Advanced Heart Failure: A Systematic Review of Criteria Used in Clinical Trials
Jonathan B Bjork1, Kristina K Alton1, Vasiliki V Georgiopoulou1
1Emory University, Atlanta, Georgia.
Insights
Defining advanced heart failure (HF) for clinical trials lacks consensus. Current criteria, including New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF), show significant variation, hindering consistent research in HF.
Area of Science:
- Cardiology
- Clinical Trials
- Heart Failure Research
Background:
- A consensus definition for advanced heart failure (HF) is currently lacking.
- Enrollment criteria in HF clinical trials may offer insights into common quantitative characteristics.
- Standardized definitions are crucial for advancing HF research and treatment.
Purpose of the Study:
- To identify common quantitative characteristics used in advanced HF clinical trials.
- To assess the consistency and variation in enrollment criteria for advanced HF.
- To inform the development of a consensus definition for advanced HF.
Main Methods:
- A systematic review of clinical trials investigating interventions in advanced HF patients was conducted.
- Publications reporting original data and explicitly defining advanced HF were included (N=134).
- Data were analyzed up to July 31, 2015.
Main Results:
- New York Heart Association (NYHA) class (88.8%) and left ventricular ejection fraction (LVEF) (62.7%) were the most common criteria.
- Significant variation was observed in cutoff points for LVEF (20%-45%) and other quantitative measures.
- Recent trials increasingly required previous HF admissions, while hemodynamic criteria use decreased.
Conclusions:
- There is considerable variation in defining advanced HF for clinical trials.
- Beyond NYHA class and LVEF, numerous criteria are inconsistently applied.
- Lack of consistency in criteria selection and cutoff points complicates advanced HF research.
Background:
Enrollment criteria used in advanced heart failure (HF) clinical trials might identify a common set of widely accepted quantitative characteristics as the basis of a consensus definition for advanced HF, which is currently lacking.
Methods:
We reviewed all clinical trials investigating interventions in patients with advanced HF as of July 31, 2015. Eligible publications (N = 134) reported original data from clinical trials explicitly defining advanced HF in adults.
Results:
New York Heart Association (NYHA) class was the most common criterion (119 trials, 88.8%; classes ranged from II to IV), followed by left ventricular ejection fraction (LVEF) (84 trials, 62.7%; cutoff range, 20% to 45%; mode 35%). Other criteria included inotrope-dependent status (12.7%), peak oxygen consumption (10.4%), ≥1 previous HF admissions (10.4%), cardiac index (10.4%), pulmonary capillary wedge pressure (9.0%), left ventricular end-diastolic diameter (6.0%), and transplant listing status (5.2%). Cutoff points for quantitative criteria varied considerably. Previous HF admission was more frequently required in recent trials (P = .007 for temporal trend), whereas use of hemodynamic criteria decreased over time (P = .050 for temporal trend). Average LVEF among participants increased over time.
Conclusions:
There is considerable variation in the definition of advanced HF for clinical trial purposes. Beyond NYHA and LVEF, a wide array of criteria has been used, with little consistency both in criteria selection and quantitative cutoff points.
