En Ping Yap1,2,3, Myu Mai Ja Kp1, Chrishan J Ramachandra4,5. 1. National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore. 2. Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore. 3. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore. 4. National Heart Research Institute Singapore, National Heart Centre Singapore, 5 Hospital Drive, Singapore, 169609, Singapore. chrishan.ramachandra@nhcs.com.sg. 5. Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, 8 College Road, Singapore, 169857, Singapore. chrishan.ramachandra@nhcs.com.sg.
Abstract
PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality. The current mechanistic paradigm supports a comorbidity-driven systemic proinflammatory state that evokes microvascular and myocardial dysfunction. Crucially, diabetes and obesity are frequently prevalent in HFpEF patients; as such, we review the involvement of a metabolic-inflammatory circuit in disease pathogenesis. RECENT FINDINGS: Experimental models of diastolic dysfunction and genuine models of HFpEF have facilitated discovery of underlying drivers of HFpEF, where metabolic derangement and systemic inflammation appear to be central components of disease pathophysiology. Despite a shared phenotype among these models, molecular signatures differ depending on type and combination of comorbidities present. Inflammation, oxidative stress, hypertension, and metabolic derangements have been positioned as therapeutic targets to suppress the metabolic-inflammatory circuit in HFpEF. However, the stratification of unique patient phenogroups within the collective HFpEF subgroup argues for specific interventions for distinct phenogroups.
PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) is a leading cause of morbidity and mortality. The current mechanistic paradigm supports a comorbidity-driven systemic proinflammatory state that evokes microvascular and myocardial dysfunction. Crucially, diabetes and obesity are frequently prevalent in HFpEF patients; as such, we review the involvement of a metabolic-inflammatory circuit in disease pathogenesis. RECENT FINDINGS: Experimental models of diastolic dysfunction and genuine models of HFpEF have facilitated discovery of underlying drivers of HFpEF, where metabolic derangement and systemic inflammation appear to be central components of disease pathophysiology. Despite a shared phenotype among these models, molecular signatures differ depending on type and combination of comorbidities present. Inflammation, oxidative stress, hypertension, and metabolic derangements have been positioned as therapeutic targets to suppress the metabolic-inflammatory circuit in HFpEF. However, the stratification of unique patient phenogroups within the collective HFpEF subgroup argues for specific interventions for distinct phenogroups.
Authors: Gregory A Roth; Mohammad H Forouzanfar; Andrew E Moran; Ryan Barber; Grant Nguyen; Valery L Feigin; Mohsen Naghavi; George A Mensah; Christopher J L Murray Journal: N Engl J Med Date: 2015-04-02 Impact factor: 91.245
Authors: Kelly McHugh; Adam D DeVore; Jingjing Wu; Roland A Matsouaka; Gregg C Fonarow; Paul A Heidenreich; Clyde W Yancy; Jennifer B Green; Natasha Altman; Adrian F Hernandez Journal: J Am Coll Cardiol Date: 2019-02-12 Impact factor: 24.094
Authors: Piotr Ponikowski; Adriaan A Voors; Stefan D Anker; Héctor Bueno; John G F Cleland; Andrew J S Coats; Volkmar Falk; José Ramón González-Juanatey; Veli-Pekka Harjola; Ewa A Jankowska; Mariell Jessup; Cecilia Linde; Petros Nihoyannopoulos; John T Parissis; Burkert Pieske; Jillian P Riley; Giuseppe M C Rosano; Luis M Ruilope; Frank Ruschitzka; Frans H Rutten; Peter van der Meer Journal: Eur J Heart Fail Date: 2016-05-20 Impact factor: 15.534
Authors: Markus Haass; Dalane W Kitzman; Inder S Anand; Alan Miller; Michael R Zile; Barry M Massie; Peter E Carson Journal: Circ Heart Fail Date: 2011-02-24 Impact factor: 8.790
Authors: Justin B Echouffo-Tcheugui; Haolin Xu; Adam D DeVore; Phillip J Schulte; Javed Butler; Clyde W Yancy; Deepak L Bhatt; Adrian F Hernandez; Paul A Heidenreich; Gregg C Fonarow Journal: Am Heart J Date: 2016-08-27 Impact factor: 4.749
Authors: Koen W Streng; Jan F Nauta; Hans L Hillege; Stefan D Anker; John G Cleland; Kenneth Dickstein; Gerasimos Filippatos; Chim C Lang; Marco Metra; Leong L Ng; Piotr Ponikowski; Nilesh J Samani; Dirk J van Veldhuisen; Aeilko H Zwinderman; Faiez Zannad; Kevin Damman; Peter van der Meer; Adriaan A Voors Journal: Int J Cardiol Date: 2018-07-07 Impact factor: 4.164
Authors: Jasper Tromp; B Daan Westenbrink; Wouter Ouwerkerk; Dirk J van Veldhuisen; Nilesh J Samani; Piotr Ponikowski; Marco Metra; Stefan D Anker; John G Cleland; Kenneth Dickstein; Gerasimos Filippatos; Pim van der Harst; Chim C Lang; Leong L Ng; Faiez Zannad; Aelko H Zwinderman; Hans L Hillege; Peter van der Meer; Adriaan A Voors Journal: J Am Coll Cardiol Date: 2018-09-04 Impact factor: 24.094