Cardiac contractility index identifies systolic dysfunction in preserved ejection fraction heart failure

medRxiv

Abstract

Abstract Background Left ventricular ejection fraction (LVEF) has well-known limitations including modest reproducibility, load dependence, and representation of the percentage change in left ventricular (LV) volume rather than myocardial contractility. We aimed to assess the prognostic value of systolic blood pressure: indexed left ventricular end-systolic volume ratio, or ‘cardiac contractility index’ (CCI). Methods We conducted a prospective cohort study in 728 unselected individuals newly diagnosed with chronic heart failure. We divided patients into tertiles of LVEF and CCI, and also divided those with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) by the median value of CCI (4.43mmHg/ml/m 2 ) into four groups. Mortality rates for CCI and LVEF as continuous variables were assessed using unadjusted and adjusted Poisson regression models. Results There was a modest, positive correlation between LVEF and CCI (r=0.70 [0.66-0.74], R 2 0.49; p <0.0001), although the latter was distributed widely for any given value of LVEF, especially for those with HFpEF. We observed distinct clinical characteristics across tertiles of both LVEF and CCI, with an inverse relationship with conventional markers of risk including N-terminal B-type natriuretic peptide ( p <0.001 in both comparisons). There was a clear relationship between tertiles of CCI and all-cause mortality risk, which was less evident when patients were divided by LVEF. When modelled as continuous variables there was a curvi-linear relationship between all-cause mortality rates and CCI, but the relationship between LVEF and mortality risk was more complex, with no clear association across a wide range from 25-55%. In models including relevant covariates, the association between LVEF and mortality was no longer evident except for those with LVEF 60% (relative to 50%) but remained evident for all specified values of CCI. Patients with HFpEF and CCI below the median value had an all-cause mortality risk ∼40% higher than those with CCI above median ( p <0.001), similar to those with HFrEF. Conclusions CCI is a non-invasive, relatively afterload independent measure left ventricular contractility which provided additional prognostic information beyond conventional assessment by LVEF. Furthermore, CCI was able to reclassify around a third of patients with HFpEF, and these patients had distinct characteristics and a worse prognosis. Clinical perspective What’s new? In an unselected population with chronic heart failure, cardiac contractility index (CCI) provided better prognostic accuracy than left ventricular ejection fraction. CCI was able to reclassify around a third of patients with a preserved ejection fraction who had evidence of reduced left ventricular contractility, and these patients had distinct characteristics and all-cause mortality risk similar to those with a reduced ejection fraction. What are the clinical implications? CCI is a simple, relatively afterload independent measure of left ventricular contractility, which utilises data already part of a standard echocardiographic assessment. The identification of subtle or concomitant systolic dysfunction in heart failure with a preserved ejection fraction may help better define risk and refine the phenotypic classification of this heterogenous group.

Authors 14

1. Sam Straw

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

2. Charlotte A. Cole

   Leeds Teaching Hospitals NHS Trust

   Affiliation as printed

   Leeds Teaching Hospitals NHS Trust

3. Oliver Ian Brown

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

4. Judith E. Lowry

   Leeds Teaching Hospitals NHS Trust

   Affiliation as printed

   Leeds Teaching Hospitals NHS Trust

5. Maria F. Paton

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

6. Ruth Vassar Burgess

   Leeds Teaching Hospitals NHS Trust

   Affiliation as printed

   Leeds Teaching Hospitals NHS Trust

7. Michael Drozd

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

8. Thomas A Slater

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

9. Samuel David Relton

   University of Leeds

   Affiliation as printed

   Leeds Institute of Health Sciences, University of Leeds, Leeds, UK

10. Richard M. Cubbon

    University of Leeds

    Affiliation as printed

    Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

11. Eylem Levelt

    University of Leeds

    Affiliation as printed

    Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

12. Klaus Karl Witte Aachen Department of Internal Medicine I (Cardiology)

    University of Leeds · Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Dept. of Internal Medicine I, University Clinic, RWTH Aachen University, Aachen, DE

    Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

13. Mark T. Kearney

    University of Leeds

    Affiliation as printed

    Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

14. John Gierula corresponding

    University of Leeds

    Affiliation as printed

    Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK