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

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/m2) 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], R2 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.

Competing Interest Statement

SS has received non-financial support from Astra Zeneca. KKW has received personal fees from Medtronic, Cardiac Dimensions, Novartis, Abbott, BMS, Pfizer, Bayer and has received an unconditional research grant from Medtronic. MTK has received personal fees from Astra Zeneca and a research grant from Astra Zeneca. JG has received personal fees from Abbott, Medtronic and Microport and has received an unrestricted research grant from Medtronic. None of the other authors have conflicts of interest to declare.

Funding Statement

This study was supported by a British Heart Foundation Clinical Research Training Fellowship awarded to Dr Sam Straw (FS/CRTF/20/24071).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The United Kingdom Health Research Authority provided ethical approval for the study through a Section 251 application reviewed by the Confidential Advisory Group. Approval through a Section 251 application allows individual patient data to be used for health service improvement and waives the requirement for individual patient consent (CAG8-03(PR1)/2013). Appropriate data safeguards were in place and the study complied with the principles outlined in the Declaration of Helsinki.

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Yes

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Data Availability

The datasets generated and/or analysed during the current study are not publicly available due to the inclusion of potentially identifiable information but are available from the corresponding author upon reasonable request.

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