The Approach to Patients with Heart Failure and Mid-Range (40-50%) Ejection Fraction (HFmrEF) 22 nd Annual Heart Failure 2018 an Update on Therapy April 21, 2018 Los Angeles, CA Barry Greenberg, M.D. Distinguished Professor of Medicine Director, Advanced Heart Failure Treatment Program University of California, San Diego
Types of Heart Failure
Distribution of EF in HF Patients HFrEF HFpEF Delepaul et al. ESC HF. 2017 May; 4(2): 99 104
The Proportion of Patients With HFmrEF Has Remained Constant Ambrosy AP et al. J Am Coll Cardiol 2014;63:1122-33
Characterization of HFmrEF Patients Optimize-HF Registry data show that demographic characteristics, symptom profile, laboratory abnormalities, comorbidities and short term outcomes were more similar to HFpEF 1. GWTG data also showed that while HFmrEF patients had characteristics that were midway between HFrEF and HFpEF patients, they more closely resembled HFpEF 2. Notably, HFmrEF had CAD profile more characteristic to HFrEF 2. 1. Fonarow G et al. JACC 2007:50;768-77. 2.Cheng R et al Am Heart J 2014:168:721-730.
Types of Heart Failure Classification Ejecti on Fracti on Description I. Heart Failure with Reduced Ejection Fraction (HFrEF) 40% Also referred to as systolic HF. Randomized clinical trials have mainly enrolled patients with HFrEF, and it is only in these patients that efficacious therapies have been demonstrated to date. II. Heart Failure with Preserved Ejection Fraction (HFpEF) 50% Also referred to as diastolic HF. Several different criteria have been used to further define HFpEF. The diagnosis of HFpEF is challenging because it is largely one of excluding other potential noncardiac causes of symptoms suggestive of HF. To date, efficacious therapies have not been identified. a. HFpEF, Borderline 41% to 49% These patients fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of patients with HFpEF. b. HFpEF, Improved >40% It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients. Yancy CW, et al. J Am Coll Cardiol. 2013;62:1495-1539.
Management of HFpEF and HFmrEF 2016 ESC Guidelines
HFmrEF Why Is It Important? Between 13% and 24% of HF patients have EF below 0.50 but above 0.40, suggesting that there are ~1.6 million HFmrEF in the U.S. alone. These patients have largely been excluded from clinical trials that have focused on patients with HFrEF (usually defined as EF <0.35) or HFpEF (usually defined as EF >0.50). Consequently there is a lack of information about this population and little evidence from RCT s and minimal input from guidelines to help direct therapy.
Outcomes Should Be Pretty Good in These Patients Just Like in HFpEF Patients. Right?
Outcomes in HFmrEF Delepaul et al. ESC HF. 2017 May; 4(2): 99 104
Median Survival in HF Patients According to Age Shah KS et al, Journal of the American College of Cardiology, Volume 70, Pages 2476-2486
Is HFmrEF A Distinct Entity?
HF Patients Experience Changes in EF Over Time* HFpEF patients tend to experience reduction in EF over time 39% of HFrEF patients had an EF >0.50 at some time during followup *1233 Olmstead Cty pts followed over 5.1 years Dunlay S et al. Circ HF 2012:5;720-726
Likelihood of Improving EF IMPROVE-HF 29% of patients had >10% improvement Wilcox, J et al. Am Heart J 163, 2012, 49 56.e2
EF Changes Over Time Proportion of patients with improved, unchanged, or worsened ejection fraction (EF) category during follow-up. Ola Vedin et al. Circ Heart Fail. 2017;10:e003875
Is HFmrEF A Distinct Entity? EF is subject to both biological and technical variability. Since EF changes over time, the HFmrEF population is a heterogeneous mix of HFpEF patients with some systolic dysfunction, patients progressing to HFrEF and patients recovering from HFrEF. EF alone provides limited information and other variables including LV size, presence of hypertrophy and fibrosis, biomarkers, and symptoms would provide more precise characterization of patients. Designating someone as having HFmrEF tells us nothing about the etiology of their disease or mechanisms involved. Co-morbidities should be considered in characterizing HFmrEF patients and in defining the treatment strategy for each patient.
Therapeutic Strategies for HFmrEF Patients
Characterization of HFpEF, HFmrEF and HFrEF
Should Neurohormonal Blocking Agents Be Maintained in HFrEF Patients Who Improve Their EF?
Left Ventricular Ejection Fraction Can Deteriorate After Recovery Included 174 pts whose EF increased to >0.45 after beta blocker therapy. Over time, 26% of patients had EF<0.45 EF deterioration predicted by high LV EDD, low HR after beta blockade and LBBB Pascal de Groote et al. Circ Heart Fail. 2014;7:434-439
Adverse Effects of Beta Blocker Withdrawal Swedberg K et al. Br Heart J 1980:44;134-42
Should Neurohormonal Blocking Agents Be Maintained in HFrEF Patients Who Improve Their EF? Yes, patients with incomplete recovery remain at risk for maladaptive remodeling of their heart and progressive LV dysfunction in the future.
Should MRA s Be Used In Patients With EF Between 40-50?
Spironolactone Failed to Demonstrate Clinical Benefit for the Primary Endpoint in TOPCAT Pitt B, et al. N Engl J Med 2014;370:1383-1392.
TOPCAT: Regional Outcomes Pfeffer MA, et al. Circulation 2015;131:34-42.
Influence of EF on Outcomes in TOPCAT Solomon S et al. Eur Heart J. 2016 Feb 1;37(5):455-62
Are Natriuretic Peptide Levels Useful in Guiding Therapy in Patients with HFmrEF?
Risk for Mortality, HF Hospitalization and Composite Outcome According to Change in NT-proBNP) Levels Gianluigi Savarese et al. Circ Heart Fail. 2016;9:e003105
Association Between Changes in NT-proBNP from Baseline to Follow-up and Risk Gianluigi Savarese et al. Circ Heart Fail. 2016;9:e003105
Does Presence of CAD and Atrial Fibrillation Influence Outcome in HFmrEF Patients?
Associations Between HF Type and Baseline Ischemic Heart Disease (IHD). Likelihood of IHD was similar in HFmrEF and HFrEF patients and patients in both of these groups were more likely to have IHD than HFpEF patients Ola Vedin et al. Circ Heart Fail. 2017;10:e003875
Influence of Ischemic Heart Disease on Change in EF Over Time Proportion of patients with improved, unchanged, or worsened ejection fraction (EF) over time according to baseline heart failure (HF) type, baseline ischemic heart disease (IHD) status, and interim IHD events. Ola Vedin et al. Circ Heart Fail. 2017;10:e003875
Presence of CAD Influences Survival in HF Patients European Journal of Heart Failure 25 SEP 2017
Atrial Fibrillation in HF Patients According to EF and Gender Sartipy L et al. JACC:HF: 5; 566-574, 2017
Atrial Fibrillation Is Association With Increased Risk Regardless of EF Sartipy L et al. JACC:HF: 5; 566-574, 2017
Management of Patients With HFmrEF Manage risk factors for CV disease and congestive symptoms as with other forms of HF. If patients have recovered from HFrEF maintain neurohormonal blockade and other therapies. MRA appears to be effective (TOPCAT). For patients whose EF is dropping strongly consider ACEI/ARB/BB. Recognize and treat co-morbidities (e.g. CAD and atrial fibrillation).? Use natriuretic peptide levels to guide therapy