Myocardial contractile dysfunction associated with increased 3-month and 1-year mortality in hospitalized patients with heart failure and preserved ejection fraction

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Abstract

Background

There is a clinical need for a contractility index that reflects myocardial contractile dysfunction even when ejection fraction (EF) is preserved. We used novel relative load-independent global and regional contractility indices to compare left ventricular (LV) contractile function in three groups: heart failure (HF) with preserved ejection fraction (HFPEF), HF with reduced ejection fraction (HFREF) and normal subjects. Also, we determined the associations of these parameters with 3-month and 1-year mortality in HFPEF patients.

Methods

199 HFPEF patients [median age (IQR): 75 (67–80) years] and 327 HFREF patients [69 (59–76) years] were recruited following hospitalization for HF; 22 normal control subjects [65 (54–71) years] were recruited for comparison. All patients underwent standard two-dimensional Doppler and tissue Doppler echocardiography to characterize LV dimension, structure, global and regional contractile function.

Results

The median (IQR) global LV contractility index, dσ*/dtmax was 4.30 s 1 (3.51–4.57 s 1) in normal subjects but reduced in HFPEF [2.57 (2.08–3.64)] and HFREF patients [1.77 (1.34–2.30)]. Similarly, median (IQR) regional LV contractility index was 99% (88–104%) in normal subjects and reduced in HFPEF [81% (66–96%)] and HFREF [56% (41–71%)] patients. Multi-variable logistic regression analysis on HFPEF identified sc-mFS < 76% as the most consistent predictor of both 3-month (OR = 7.15, p < 0.05) and 1-year (OR = 2.57, p < 0.05) mortality after adjusting for medical conditions and other echocardiographic measurements.

Conclusion

Patients with HFPEF exhibited decreased LV global and regional contractility. This population-based study demonstrated that depressed regional contractility index was associated with higher 3-month and 1-year mortality in HFPEF patients.

Introduction

Heart failure with preserved ejection fraction (HFPEF), also called diastolic heart failure, is a major and growing public health problem which represents one third to half of patients with HF [1]. Assessment of left ventricular (LV) contractile function is important for HF management and evaluation of medical and surgical therapies. Numerous studies have reported that regional systolic function assessed by Tissue Doppler imaging and speckle tracking echocardiography is impaired in HFPEF despite normal LV ejection fraction (EF) [2], [3], [4], [5], [6], [7]. However, the clinical relevance of these abnormalities has been questioned owing to load- and geometry-dependent measures of systolic function [8], [9].

We have recently evaluated a novel global LV load-independent contractility index, dσ*/dtmax (maximal rate of change in pressure-normalized wall stress) that correlates well with LV end-systolic elastance (Ees) and maximal first derivative of ventricular pressure dP/dtmax [10]. We have used the global index to evaluate the effect of surgical treatment in HF patients [11]. We have also used it in a small number of patients to identify HFPEF [12]. Stress-corrected mid-wall shortening (sc-mFS) is a relative, load-independent regional contractility index used to assess LV regional contractile function. Sc-mFS has demonstrated sensitivity in diagnosing HFPEF [3]. Using these indices, we compared both global and regional LV contractility among 3 patient groups: HFPEF, HF with reduced ejection fraction (HFREF) and normal controls. The study also investigated associations of global and regional LV contractility with 3-month and 1-year mortality in HFPEF patients.

Section snippets

Patients

A prospective consecutive hospital-based heart failure (HF) registry was designed to compile a large clinical database on the medical management of HF from 01 Jan 2008 to 31 December 2008 at National Heart Centre Singapore. A total of 526 patients from total HF registry population (N = 1081) who survived till discharge from the hospital and had clinically-indicated good-quality echocardiographic images were recruited into the study. Additionally, 22 normal control subjects who presented for a

Demographics

Overall 548 participants were recruited. Of these, there were 526 HF patients (305 males and 221 females) with median age 70 years (IQR: 60–78 years). Hypertension (70.5%) and diabetes mellitus (47.5%) were the most common associated comorbidities of HF.

Baseline characteristics of patients with HFPEF and HFREF, and normal controls are summarized in Table 1. HFPEF patients were older than HFREF patients (75 vs. 69 years; p < 0.0001) with a higher proportion of females (58 vs. 32%; p < 0.0001) and

Discussion

In our study, one third of our HF patients had preserved EF. Patients with HFPEF had impaired global and regional LV contractility, as evidenced by reduced dσ*/dtmax and sc-mFS, despite a normal LV ejection fraction. The prognosis of HFPEF was similar to HFREF with 1-year mortality of about 15%. Impaired sc-mFS was associated with increased mortality at both 3-months and 1-year in HFPEF patients.

Conclusions

Although EF is preserved (“normal”) in patients with HFPEF, left ventricular contractility is impaired at both global and regional levels as demonstrated by dσ*/dtmax and sc-mFS, respectively. Stress-corrected midwall fraction shortening (sc-mFS < 76%) was strongly associated with both increased 3-month and 1-year mortality in patients with HFPEF.

Acknowledgments

This work was supported in part by a research grant from the National Heart Centre Singapore Health Endowment Fund and from National Medical Research Council (NMRC), NMRC/NIG/1006/2009 (L Zhong). We acknowledge the support of A/Prof Kian Keong Poh for the echocardiographic measurements of normal subjects (Cardiac department, National University Hospital, Singapore). We also appreciate the support of the SingHealth/Duke-NUS Academic Medicine Research Institute Singapore and assistance of Taara

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