MAGGIC Confirms Lower Mortality in Preserved-EF Heart Failure

September 02, 2009

September 2, 2009 (Barcelona, Spain) — A new individual patient-data meta-analysis has clearly shown that those with HF with preserved ejection fraction (HFPEF) have a lower mortality than HF patients with impaired EF. Dr Robert N Doughty (University of Auckland, New Zealand) presented the findings of the Meta-Analysis Global Group in CHF (MAGGIC) study during a clinical-trial update session at the European Society of Cardiology 2009 Congress.

"We hope this data set will help to characterize those with preserved-EF heart failure much better and that this, hopefully, will lead to targeted therapies for those patients," Doughty told heartwire . "That's the message--this is a heterogeneous group of patients that we need to specifically target therapies to, as opposed to just treating everybody the same."

That's the message--this is a heterogeneous group of patients that we need to specifically target therapies to, as opposed to just treating everybody the same.

Much of the problem, he explained, is that those with HFPEF "typically present with the same symptoms and clinically they look the same [as those with impaired-EF HF]." In MAGGIC, he and his colleagues did manage to identify some clinical pointers: "We found that preserved-EF HF patients are slightly older and more frequently women and more often have a history of hypertension and less often one of coronary artery disease than those with low EF." And they discovered that mortality only really starts to increase below an EF of 40%.

Discussant of the MAGGIC results, Dr David M Kaye (Baker Heart Research Institute, Melbourne, Australia) said the study clearly indicates "that there are two heterogeneous populations of patients with different LV biology and that survival is significantly better in those with preserved EF," but it leaves "many unanswered questions."

Next Step Is to Identify Predictors of Outcome

Doughty explained that MAGGIC was conducted because individual studies have reported variable results in relation to total mortality in patients with HFPEF. Using a data set of 43 373 patients, including registry data and randomized clinical trials, Doughty and colleagues found that around 25% of patients with a measurable EF could be classified as having HFPEF, defined as left ventricular EF of 50% or greater. They also discovered, Doughty said, that "missing EF data" are common in clinical trials.

They found a much lower mortality among those with HFPEF than those with impaired-EF heart failure–-hazard ratio 0.68 (95% CI 0.65–0.72), a highly significant finding. This compares with an HR of 0.53 (95% CI 0.46–0.60) for a similar comparison in a parallel analysis from CHARM-PRESERVED, conducted for the MAGGIC investigators by the London School of Hygiene and Tropical Medicine, Doughty said. Those with an EF of between 40% and 50% essentially had the same death rate as those with EF of 50% and above.

This "unique data set" will be used for further analysis, Doughty explained, including modeling of outcomes in those with missing EF data. "Other work will involve identifying predictors of outcomes in those with preserved-EF HF, with the ultimate aim of improving the identification of patients with a high risk of death and hospitalization in this increasingly recognized condition."

Kaye said the questions at a practical, clinical level on how to deal with these patients include whether it is possible to add biomarkers that would improve prediction of outcome in these patients and whether those at high risk of sudden cardiac death can be more easily identified.

Control of Symptoms Also an Unmet Goal

"Beyond survival, for these older patients, hospitalization and control of symptoms is clearly a goal, and by and large clinical trials to date have not yielded positive results," Kaye added.

"This study raises many important questions that behoove us to think about the mechanisms responsible not only for outcome in terms of survival, but for symptoms in these patients--the pathophysiology of HF with preserved EF is extremely complex, as we are only just learning."

For example, the heart-rate response to exercise is important and is currently being addressed in pacing studies, he noted. And aggressive treatment of confounding factors, such as ischemia and atrial fibrillation, "are also clearly highly important in this group of patients," he said.

Also essential are noncardiac factors, such as adequately managing the plasma volume in these patients and addressing key issues such as ventricular/vascular coupling, "which will provide new and potentially therapeutic gains for the management of these patients," Kaye concluded.

To access complete presentation slides (pdfs), click here.