Heart failure with reduced and preserved ejection fraction. Clinical and translational aspects

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Lars H Lund Research Group

Associated

Lars Lund

Phone: +46-(0)8-517 749 75
E-mail: Lars.Lund@ki.se

Research questions:

1. Heart failure with preserved ejection fraction (HFPEF): demographics, risk factors, comorbidity and cause specific morbidity and mortality, treatment targets and interventional trial design

2. HFPEF: potential effects of conventional drugs used for heart failure with reduced ejection fraction, e.g. ACE-inhibitors, angiotensin receptor blockers, beta-blockers and aldosterone antagonists

3. Physiologic, neurohormonal and metabolic aspect of heart failure with preserved and reduced ejection fraction, and effects of heart transplantation and mechanical circulatory support (LVAD and ECMO)

4. Molecular cardiac and skeletal muscle changes in heart failure and targets for treatments to modify contraction-relaxation

5. Early phase human interventional trials of existing drugs for novel indication and of novel drugs and peptide hormones as treatment for heart failure

6. How to optimize utilization of existing therapy for heart failure with reduced ejection fraction

Our group consists of 5 PhD students, 3 post-docs, a statistician, and a research nurse. We also collaborate with other groups at Karolinska nationally, and numerous groups internationally. We are involved in epidemiological, clinical and molecular aspects of heart failure.

Heart failure affects 2-3% of the Western population and with an ageing population, this number will grow. It is associated with poor quality of life, is the most common cause of hospitalization in patients > age 65, more lethal than cancer, and associated with high costs to society. Neurohormonal antagonist drugs (e.g. ACE inhibitors, beta blockers) improve symptoms and survival in heart failure with reduced ejection fraction (HFREF or “systolic heart failure”) and represent one of the greatest evidence based successes in modern medicine.

However, we are focus on two major current clinical problems that have not been addressed:

1. Despite neurohormonal drugs, up to 1/3 of patients with heart failure with reduced ejection fraction are still very ill with poor prognosis. Additional mechanisms of disease and target of therapy are explored. There are more advanced therapies (CRT, ICD, heart transplant and LVAD and ECMO (mechanical heart pump)) but the utilization of these is inadequate.

2. Heart failure with preserved ejection fraction (HFPEF or “diastolic heart failure”) is increasingly recognized as equally common and equally lethal as heart failure with reduced ejection fraction. However, mechanisms are poorly understood and there is currently no proven therapy.

We perform registry based research with the Swedish Heart Failure Registry (RiksSvikt) and the International Society for Heart & Lung Transplantation (ISHLT) adult heart transplant registry, as well as numerous international collaborative clinical studies. We have a complete non-invasive human physiology lab where we characterize heart failure with preserved and reduced ejection fraction and assess physiologic effects of interventions. We also perform mechanistic studies where we study peripheral hormones involved in heart failure and molecular aspects of contraction-relaxation in vitro.

Individuals interested in pursuing mechanistic, clinical or registry based research in the field of heart failure are welcome to contact our group. 

Selected references

Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction.
Lund L, Benson L, Dahlström U, Edner M
JAMA 2012 Nov;308(20):2108-17

 Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction.
Lund L, Jurga J, Edner M, Benson L, Dahlström U, Linde C, et al
Eur. Heart J. 2013 Feb;34(7):529-39

 Association of candesartan vs losartan with all-cause mortality in patients with heart failure.
Eklind-Cervenka M, Benson L, Dahlström U, Edner M, Rosenqvist M, Lund L
JAMA 2011 Jan;305(2):175-82

 Triage of patients with moderate to severe heart failure: who should be referred to a heart failure center?
Thorvaldsen T, Benson L, Ståhlberg M, Dahlström U, Edner M, Lund L
J. Am. Coll. Cardiol. 2014 Feb;63(7):661-71

Modifications of skeletal muscle ryanodine receptor type 1 and exercise intolerance in heart failure.
Rullman E, Andersson D, Melin M, Reiken S, Mancini D, Marks A, et al
J. Heart Lung Transplant. 2013 Sep;32(9):925-9

Translational Medical Research