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Exercise Intolerance in Older HFPEF Patients

Award Number: R01AG018915
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2001
PERIOD OF PERFORMANCE END DATE: 03/31/2023

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Exercise Intolerance in Older HFPEF Patients - DESCRIPTION (provided by applicant): Heart failure with preserved ejection fraction (HFpEF) is the most common form of HF and is nearly unique to the older persons. Exercise intolerance is the primary manifestation of HFpEF and severely reduces quality-of- life (QOL). However, its pathophysiology is poorly understood and its optimal treatment remains undefined. Multiple lines of evidence indicate that increased adiposity and abnormalities in skeletal muscle are major contributors to exercise intolerance in older HFpEF patients. Obesity is one of the strongest risk factors for HFpEF, and 85% of older HFpEF patients have the overweight/obese phenotype. We have found that HFpEF patients have reduced total lean mass, increased thigh muscle fat infiltration, reduced capillarity and percent type I fibers, and trends for reduced mitochondrial mass and function; all of which were related to reduced peak VO2. In our recent study in obese older HFpEF patients, both caloric restriction (CR) and aerobic exercise training (AT) increased peak VO2 equally and their combination was strongly additive and improved QOL. Improved peak VO2 was related to reduced fat mass, increased percent lean mass, improved thigh muscle composition and trends for increased mitochondrial mass and function, which were greatest with CR. These data strongly support combined CR+AT as a novel treatment for HFpEF. However, about 35% of the weight lost during CR was muscle mass and was not prevented by AT. This muscle mass loss is a concern because it could have hindered the gains in peak VO2, and has been associated with increased disability, hospitalizations, and death. Thus, a logical next step is to build on our successes by finding strategies to further increase peak VO2 during CR+AT by retaining muscle mass and improving mitochondrial function. Multiple lines of evidence indicate that resistance training (RT) could be an ideal addition to CR+AT for HFpEF. In other populations, RT increases muscle mass and mitochondrial function, and increases peak VO2 in magnitude similar to AT and the two have additive and complementary effects. We reported that RT during CR in obese older non-HF adults reduces loss of muscle mass nearly 50%. In our pilot study, we found that RT improves mitochondrial function in older obese adults. However RT has not been tested in HFpEF or during CR in any type of HF. The primary aim of the proposed study is to conduct a randomized, single-blinded 24- week intervention trial of RT added to CR+AT in 100 overweight/obese (BMI > 28), HFpEF patients age >60 years to test the hypotheses that addition of resistance training to AT during CR will improve peak VO2 and will increase muscle mass. A secondary, mechanistic aim will determine if the addition of RT to CR+AT improves muscle mitochondrial function. If successful, this innovative study will define the optimal non- pharmacological intervention for exercise intolerance in the growing population of overweight/obese older HFpEF patients. It will also: advance a new paradigm regarding the role of muscle in HFpEF pathophysiology, test a novel intervention, and provide the first mechanistic insights regarding mitochondrial function in HFpEF.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$11,653 )
2024	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	18	12/13/2023	NON-COMPETING CONTINUATION	-$11,653
														Subtotal = -$11,653

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	18	4/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	18	3/8/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $784,280 )
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	18	3/21/2019	NON-COMPETING CONTINUATION	$784,280
														Subtotal = $784,280

Issue Date FY: 2018 ( Subtotal = $933,700 )
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	17	9/10/2018	SUPPLEMENT FOR EXPANSION	$154,755
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	17	4/17/2018	NON-COMPETING CONTINUATION	$778,945
														Subtotal = $933,700

Issue Date FY: 2017 ( Subtotal = $763,620 )
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	002	16	8/14/2017	SUPPLEMENT FOR EXPANSION	$138,683
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	16	4/25/2017	NON-COMPETING CONTINUATION	$562,443
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	001	16	6/20/2017	NON-COMPETING CONTINUATION	$62,494
														Subtotal = $763,620

Issue Date FY: 2016 ( Subtotal = $624,937 )
2016	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	15	4/5/2016	NON-COMPETING CONTINUATION	$624,937
														Subtotal = $624,937

Issue Date FY: 2015 ( Subtotal = $645,068 )
2015	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	14	4/9/2015	COMPETING CONTINUATION	$645,068
														Subtotal = $645,068

Issue Date FY: 2004 ( Subtotal = $350,285 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	4	7/30/2004	NON-COMPETING CONTINUATION	$350,285
														Subtotal = $350,285

Issue Date FY: 2003 ( Subtotal = $350,998 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3	6/30/2003	NON-COMPETING CONTINUATION	$350,998
														Subtotal = $350,998

Issue Date FY: 2002 ( Subtotal = $352,139 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	2	5/17/2002	NON-COMPETING CONTINUATION	$352,139
														Subtotal = $352,139

Issue Date FY: 2001 ( Subtotal = $353,911 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	1	2/1/2001	NEW	$353,911
														Subtotal = $353,911

Grand Total All Awards = $5,147,285

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Exercise Intolerance in Older HFPEF Patients

Award Number: R01AG018915

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/15/2001

PERIOD OF PERFORMANCE END DATE: 03/31/2023

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