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Obesity & Diabetes: New targets in heart failure management - - PowerPoint PPT Presentation

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Obesity & Diabetes: New targets in heart failure management Rudolf A. de Boer, MD, FESC, FHFA University Medical Center Groningen Groningen, the Netherlands Novel concepts and treatments of comorbidities in Heart Failure with Preserved

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Obesity & Diabetes: New targets in heart failure management

Rudolf A. de Boer, MD, FESC, FHFA University Medical Center Groningen Groningen, the Netherlands Novel concepts and treatments of comorbidities in Heart Failure with Preserved Ejection Fraction Sunday May 27, 12:45-14:00

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Faculty Disclosure

I I have received a research grant(s)/ in kind support

A From current sponsor(s) YES NO B From any institution YES NO

II I have been a speaker or participant in accredited CME/CPD

A From current sponsor(s) YES NO B From any institution YES NO

III I have been a consultant/strategic advisor etc

A For current sponsor(s) YES NO B For any institution YES NO

IV I am a holder of (a) patent/shares/stock ownerships

A Related to presentation YES NO B Not related to presentation YES NO

Declaration of financial interests For the last 3 years and the subsequent 12 months:

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Faculty Disclosure: Rudolf A. de Boer MD PhD

Declaration of non-financial interests:

  • University of Groningen, Groningen, the Netherlands
  • Professor of Cardiology, Cardiologist, Director of Experimental Cardiology
  • Dr. de Boer is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON

SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11); and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350).

  • Board member, Heart Failure Association (HFA) of the ESC
  • Chair, study group on HFpEF of the HFA
  • Member ESC Advocacy committee
  • Chair, working group of Heart Failure of the Dutch Society of Cardiology
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University Medical Center Groningen

1995

Obesity Trends* Among U.S. Adults BRFSS, 1990, 1995, 2005

(*BMI 30, or about 30 lbs overweight for 5’4” person) 1990 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% 2005

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University Medical Center Groningen

Overlapping risk factors

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University Medical Center Groningen

Bhambhani V, et al. Eur J Heart Fail. 2018; 20:651-659

BMI and Diabetes: Predictors for new onset HFpEF

  • 28,820 individuals from the 4 large cohort studies, 12 years of FU
  • 811 new onset HFpEF (39%)
  • 200 new onset HFmrEF (10%)
  • 1048 new onset HFrEF (51%)

FHS/PREVEND/CVS/MESA

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University Medical Center Groningen

Current pathophysiological paradigm: Obesity and DM are important drivers of HFpEF

Shah, SJ et al. Circulation. 2016; 134:73-90

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University Medical Center Groningen

Treatment of obesity

Neeland IJ, et al. Circulation. 2018; 137:1391–1406

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University Medical Center Groningen

Bariatric surgery and HFpEF

Rodriguez Flores M, et al. Expert Rev Cardiovasc Ther. 2017; 15:567-579

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University Medical Center Groningen

Obesity-related HFpEF

Packer M. JACC: Heart Failure 2018

Speculation!

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University Medical Center Groningen

Obesity paradox

Carbone S, et al. Mayo Clin Proc. 2017; 92:266-279 Padwal R, et al. Int J Obes (Lond). 2014; 38:1110-1114

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University Medical Center Groningen

Kitzman DW & Shah SJ. J Am Coll Cardiol HF. 2016; 68:200-203

Obesity: Contributor or confounder of HFpEF?

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University Medical Center Groningen

Obesity: substantial heterogeneity

Neeland IJ, et al. Circulation. 2018; 137:1391–1406

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University Medical Center Groningen

Carbone S, et al. Mayo Clin Proc. 2017; 92:266-279

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University Medical Center Groningen

Obese-HFpEF phenotype is clinically relevant

  • Obese HFpEF patients (N = 99) were compared to non-obese

HFpEF patients (N = 96) and control subjects free of HF (N = 71)

  • Characteristics of obese HFpEF patients
  • Increased plasma volume
  • More concentric LV remodeling
  • Greater RV dilation and more RV dysfunction
  • Increased epicardial fat thickness
  • Greater total epicardial heart volume

Obokata M, Circulation. 2017; 136: 6-19

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University Medical Center Groningen

Exercise capacity & hemodynamic reserve reduced in obese HFpEF patients

Obokata M, Circulation. 2017; 136: 6-19

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University Medical Center Groningen

HF and Fitness: Role of BMI

Low Cardiorespiratory Fitness High Cardiorespiratory Fitness Lavie CJ, et al. Mayo Clin Proc. 2013; 88:251-258

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University Medical Center Groningen

BMI stronger predictor for HFpEF than for HFrEF

E F M e n HFrE F W

  • me

n Women 1 2 3 4

HF subtype by quartile of BMI

HR for Incidence of HF subtype

Men Women

P=<0.001 P<0.001 P<0.001 P=0.49

HFpEF HFpEF HFrEF HFrEF

Savji N, et al. JACC Heart Fail. Accepted

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University Medical Center Groningen

Obesity and Sex: Effects on NT-proBNP

Suthahar N, et al. Eur J Heart Fail. 2018; in press PREVEND study: 8,592 subjects, mean age 49 years

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University Medical Center Groningen

Summary 1 - Obesity

  • Important to have ‘normal weight’
  • Once HFpEF: important to have sufficient lean mass
  • Losing fat mass: pharmacotherapy not useful, consider

bariatric surgery when obesity is severe and intractable

  • We need to know much more about body weight,

posture & sex differences

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University Medical Center Groningen

IDF Diabetes Atlas, 2015

Diabetes: a call for action

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University Medical Center Groningen

Bhambhani V, et al. Eur J Heart Fail. 2018; 20:651-659

BMI and Diabetes: Strong predictors of new onset HFpEF

  • 28,820 individuals from the 4 large cohort studies, 12 years of FU
  • 811 new onset HFpEF (39%)
  • 200 new onset HFmrEF (10%)
  • 1048 new onset HFrEF (51%)
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University Medical Center Groningen

HF in T2DM trials & T2DM in HF trials

Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872

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University Medical Center Groningen

Diabetes : Prognostic factor in prevalent HFpEF

Kristensen, et al. Cardiovasc Drugs Ther. 2017; 31:545-549

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University Medical Center Groningen

Current pathophysiological paradigm: Obesity and DM are important drivers of HFpEF

Shah, SJ et al. Circulation. 2016; 134:73-90

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University Medical Center Groningen

Pacher P, et al. Physiol Rev 2007; 87:315-424

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University Medical Center Groningen

Paulus & Da Canto. J Am Coll Cardiol HF. 2018; 6:1–7.

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University Medical Center Groningen

Cardiovascular phenotype of patients with HFpEF with and without Diabetes

  • RELAX trial (216 stable outpatients with HF, EF > 50%)
  • Non-diabetic (N = 123); Diabetic (N = 93)
  • Diabetic patients were
  • Younger, more often male
  • More obese
  • Higher prevalence of hypertension, renal dysfunction,

pulmonary disease & vascular disease

Lindman BR, J Am Coll Cardiol. 2014;64: 541-9

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University Medical Center Groningen

End points in HFpEF patients with and without diabetes

Lindman BR, J Am Coll Cardiol. 2014;64: 541-9

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University Medical Center Groningen

Treatment of T2DM in HF

Seferovic P, et al. Eur J Heart Fail. 2018; 20:853-872.

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Treatment of T2DM in HF

Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872.

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University Medical Center Groningen

SGLT-2 trials in HFpEF

Seferovic P, et al. Eur J Heart Fail. 2018; 20: 853-872.

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University Medical Center Groningen

Recognized Expanded Biological Effects of GLP-1

Seufert & Gallwitz; Diabetes Obes Metab. 2014 Aug;16(8):673-88.

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University Medical Center Groningen

Meta-analysis: MACE-3 endpoint

Bethel et al. Lancet Diabetes Endocrinol. 2017;6:105-113

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Meta-analysis: All-cause mortality

Bethel et al. Lancet Diabetes Endocrinol. 2017;6:105-113

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University Medical Center Groningen

Conclusion

  • Obesity and diabetes are amongst the most prevalent and

dominant co-morbidities in HFpEF

  • We do not fully understand ‘obesity’
  • No clear recommendations can be made for the treatment of

T2DM, but SGLT-2 inhibitors and GLP1RA appear effective

  • Prospective RCTs are underway
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University Medical Center Groningen

Acknowledgements & Collaborations

Clinical Cardiology

Dirk J. van Veldhuisen Pim van der Harst Hans L. Hillege Adriaan A. Voors Maarten P. van den Berg Peter van der Meer

Internal Medicine

Stephan J. Bakker Ron T. Gansevoort

Laboratory Medicine

Anneke C. Muller Kobold

Medical Biology

Ruud A. Bank Harry van Goor Peter Heeringa Marten Hofker †

University of Michigan, USA

Bertram Pitt

Free University of Amsterdam, the Netherlands Jolanda van der Velden Bianca J. Brundel University of Wageningen, the Netherlands

Henk A. Schols

Potential Conflicts of interest: Speaker/consultancy fees: Medcon, Novartis, Servier, Mandalmed Research grants: NWO-VIDI, Netherlands Heart Fourndation, AstraZeneca, BMS, Trevena Minority shareholder: scPharmaceuticals Boxford, MA, USA

Pieter Muntendam

University of California, San Diego, USA Alan S. Maisel University of Amsterdam, the Netherlands

  • J. Peter van Tintelen

Experimental Cardiology

Wiek H. van Gilst Herman H. Silljé Peter van der Meer Laura M.G. Meems Wouter C. Meijers Tim Eijgenraam Navin Suthahar Salva Yurista Arnold Piek Aad Withaar Carolin Gehlken Janny Takens Marloes Schouten

University of Maastricht, the Netherlands

  • Leon. J. de Windt

Stephane Heymans

Medical Genetics

Jan Jongbloed Irene van Langen Yvonne Hoedemaekers

University of Utrecht, the Netherlands

Frans Rutte Pieter Doevendans

Imperial College, London, UK

Alexander Lyon

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University Medical Center Groningen

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University Medical Center Groningen

Diabetic cardiomyopathy: Stage B HFpEF

  • Diabetes mellitus (DM) is a stage A risk factor for

HFpEF

  • Asymptomatic diabetic cardiomyopathy
  • Manifestation of stage B HFpEF
  • LV diastolic dysfunction in diabetic patients without

coronary artery disease, hypertension etc.

  • Can progress to stage C HFpEF

Lam CS, Diab Vasc Dis Res. 2014; 64: 541-9