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Ventricular and Atrial Ejection Fractions are Associated with Mean Compartmental Cavity Volume in Cardiac Disease
Insights
Ejection fraction (EF) is a popular metric, but its mathematical basis is questionable. This study reveals EF is strongly linked to ventricular size rather than pumping function, questioning its physiological relevance.
Area of Science:
- Cardiology
- Biomedical Engineering
- Physiology
Background:
- Ejection fraction (EF) is widely used in clinical practice despite limited understanding of its foundational principles.
- Existing research often criticizes EF's applicability, highlighting a lack of robust mathematical underpinnings.
- EF is calculated from end-systolic volume (ESV) and end-diastolic volume (EDV) as 1-ESV/EDV, a unitless metric.
Purpose of the Study:
- To analytically explore the relationship between EF and ventricular volumes.
- To investigate the association between EF and half the sum (HS) of ESV and EDV.
- To evaluate the physiological basis of EF in various cardiac compartments.
Main Methods:
- Formulated an analytical expression for the nonlinear connection between EF and ESV.
- Extended the approach to derive a formula linking EF with HS (ESV+EDV)/2.
- Analyzed data from heart failure patients (left ventricle angio, echo) and myocardial infarction patients (right and left atria).
Main Results:
- A strong correlation was found between EF and HS across different patient groups and imaging modalities (R values ranging from -0.46 to -0.82).
- EF is primarily associated with ESV, which in turn correlates highly with EDV, indicating EF reflects ventricular/atrial size.
- ESV reflects the ventricle's ability to eject blood, whereas EF represents relative volume changes, not the pumping mechanism.
Conclusions:
- EF's clinical popularity stems from the linear correlation between ESV and EDV in a broad patient spectrum.
- The attractiveness of EF is derived from its simple mathematical formulation, not its reflection of physiological function.
- EF, as a mathematical construct, has limited affinity with the physiological concept of cardiac 'function'.
Abstract:
Ejection fraction (EF) is considered to provide clinically useful information. Despite its enormous popularity, with more than 75,000 citations in PubMed, only few studies have traced the origin(s) of its foundation. This fact is surprising, as there are perhaps more papers published that criticize EF, than the number of publications that actually provide a solid (mathematical) basis for its alleged applicability. EF depends on two volume determinations, namely end-systolic volume (ESV) and end-diastolic volume (EDV). EF is defined as 1-ESV/EDV, yielding a metric without physical units. Previously we formulated a robust analytical expression for the nonlinear connection between EF and ESV. Here we extend that approach by providing a formula to illustrate that EF is strongly associated with half the sum (HS) of ESV and EDV. HS is not new, but forms a major component in the recently introduced Global Function Index. For 420 heart failure (HF) patients we found for left ventricular angio data: R(ESV, eDv) = 0.92, R(EF, ESV) = -0.90, and R(EF, HS) = -0.65. For echo (33 HF patients stages A, B, C and D): R(EF, HS) = -0.82. For the right atrium (CMRI in 21 acute myocardial infarction patients): R(EF, HS)=-0.65. For the left atrium (N=86) R (EF, hS)=-0.46. ESV indicates the level to which the ventricle is able to squeeze blood out of the cavity via pressure build-up. In contrast, EF refers to relative volume changes, not to the mechanism of pumping action. We conclude that for each cardiac compartment EF borrows its acclaimed attractiveness from the fact that for a wide patient spectrum the ESVand EDV correlate in a fairly linear manner. Attractiveness of EF features a straightforward mathematical derivation, rather than reflecting underlying physiology. Clinical Relevance - Ejection fraction (EF) is found to reflect (mean) ventricular / atrial size, and is primarily associated with end-systolic volume, which variable in turn highly correlates with diastolic volume. As a mathematical construct, EF has little affinity with "function", which is a central concept in physiology.
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