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MAGGIC: Survival in patients with heart failure and preserved versus impaired left ventricular ejection fraction: an individual patient data meta-analysis

Clinical Trial Update III

Heart Failure (HF)

Presenter | see Discussant report

Robert Doughty (New Zealand)

Presentation webcast

Presentation slides

List of Authors:
Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) Investigators


Heart failure with preserved LV ejection fraction (HF-PEF) represents an important subgroup of patients with heart failure. There has been conflicting evidence from previous studies of the outcome for patients with HF-PEF compared with patients with HF with low ejection fraction (HF-lowEF). Hypothesis That patients with HF-PEF have lower mortality than patients with HF-lowEF.

To investigate survival for patients with HF-PEF we have undertaken an individual patient meta-analysis, combining individual patient data from studies that recruited patients without an LVEF inclusion criterion and reported all-cause mortality. Data, including demographics, medical history, clinical status, LVEF, and all-cause mortality, have been submitted to a central coordinating centre (Auckland, New Zealand) and combined into one dataset. Patients were stratified into 2 groups according to LVEF cut-off: 1) LVEF ≥50% or HF-PEF; and 2) LVEF <50% or HF-lowEF. Kaplan Meier survival analysis and Cox proportional hazards adjusting for age, gender and study. A separate analysis from the CHARM Cohort was undertaken using similar methods.

Individual patient data has been submitted from 29 studies, involving 46,596 patients. 25,796 (59%) patients had HF-lowEF, 8571 (20%) HF-PEF and in 9006 (21%) patients LVEF data was missing. For the whole group, mean age 68±12 years, 36% were women, 52% had history of ischemic heart disease and 40% history of hypertension, mean LVEF 37.6 ± 15%. The patients with HF-PEF were older (72±12 vs 66±12), more were women (51% vs 28%), more had a history of hypertension (47% vs 38%) and fewer had ischemic etiology (41% vs 57%) compared with patients with HF-lowEF. During the 3 years follow up, 2154 (25%) patients with HF-PEF died compared with 6988 (27%) patients with HF-lowEF. Using Cox proportional hazards model (adjusting for age and gender and stratifying by study) the HF-PEF group had better survival than the HF-lowEF group (HR 0.68, 95% CI 0.65, 0.72; see figure). A separate analysis of the CHARM cohort using LVEF < or ≥ 50% demonstrates similar results with the HF-PEF group having better survival than the HF-lowEF group (HR 0.53, 95% CI 0.46, 0.60).

This analysis from a large individual patient data meta-analysis demonstrated that patients with HF-PEF had better survival than patients with HF-lowEF (similar to that observed in the CHARM cohort). Further clarification of predictors of outcome among patients with HF-PEF may allow future interventions to target high risk subgroups of patients with HF-PEF.


Survival in patients with heart failure and preserved versus impaired left ventricular ejection fraction



Discussant | see Presenter abstract

David Martin Kaye (Australia)

Presentation webcast

Presentation slides


The widespread availability of sophisticated diagnostic tools including 2D, Doppler and strain echocardiography and cardiac magnetic resonance imaging together with biomarkers such as brain natriuretic peptide (BNP) has significantly contributed to a major change in the way in which the diagnosis of heart failure (HF) is made. Ostensibly, HF is a clinical diagnosis based upon the recognition of the classic symptoms and signs including dyspnea, oedema and fatigue. Following clinical assessment, the rationale for the application of the various investigative techniques in HF patients includes the confirmation of the diagnosis, the development of therapeutic strategies and to provide prognostic information.

Coincident with the application of techniques such as echocardiography to large numbers of patients with HF symptoms or in cross-sectional population studies, it has become evident that approximately half of the HF patients have a normal or near normal left ventricular ejection fraction (HFNEF). In conjunction, these patients exhibit many demographic differences to patients with reduced EF HF (HFREF) including advanced age, history of hypertension, obesity, renal impairment and female gender.

Although the distinction between HFNEF and HFREF is now widely accepted, this classification has been the genesis of many more questions. In particular, in contrast to HFREF, the natural history and pathophysiology of HF remains the subject of ongoing debate and in conjunction current therapies for HFNEF are far from satisfactory.

The MAGGIC study investigators sought to investigate whether prognosis of HFNEF differs to that for HFREF patients, a point that has recently been debated in the literature. By analyzing a large number of prospective and comparative studies the investigators show in this study that the prognosis is worse for HFREF patients compared to HFNEF and in this large dataset that LVEF is a key prognostic index, particularly under 30-40%. As observed in other HFNEF studies, affected patients were more likely to be older and to have a history of hypertension.

As such, the MAGGIC study serves to remind us that HFNEF patients differ significantly from HFREF patients in many ways, and as a corollary only by clearly understanding its pathophysiology will it be possible to apply or develop specifically targeted therapy.




Survival in patients with heart failure and preserved versus impaired left ventricular ejection fraction: an individual patient data meta-analysis: MAGGIC

Notes to editor

This congress report accompanies a presentation given at the ESC Congress 2009. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.