New therapeutic targets for stages of

heart failure based on diet compounds

and local fat development

Cardiology Group

(Health Research Institute)

Sonia Eiras Penas

Deaths by cause in men and women, Europe

European Cardiovascular Disease Statistics 2012

Coronary Heart

Disease 20%

Stroke 10%

Other CVD 12%

Stomach cancer

2% Colo-rectal

cancer 2%

Lung cancer

4%

Other cancer

13% Respiratory disease

7%

Injuries and

poisoning 10%

All other causes

20%

Coronary Heart

Disease 22%

Stroke 15%

Other CVD 15%

Stomach cancer

1% Colo-rectal

cancer 2%

Lung cancer

2%

Breast cancer

3%

Other cancer

10%

Respiratory disease

6%

Injuries and

poisoning 4%

All other causes

20%

52%

Heart Failure

The main cause of morbidity in the world and remains the most

frequent cause of hospitalization for patients over 65 years old.

Braunschweig F et al. Europace 2011;13:ii13-ii17

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author

2011. For permissions please email: journals.permissions@oup.com.

Costs for heart failure in the USA from 2003 to 2010

Stages, Phenotypes and Treatment of HF

STAGE AAt high risk for HF but

without structural heart

disease or symptoms of HF

STAGE BStructural heart disease

but without signs or

symptoms of HF

THERAPY

Goals

· Control symptoms

· Improve HRQOL

· Prevent hospitalization

· Prevent mortality

Strategies

· Identification of comorbidities

Treatment

· Diuresis to relieve symptoms

of congestion

· Follow guideline driven

indications for comorbidities,

e.g., HTN, AF, CAD, DM

· Revascularization or valvular

surgery as appropriate

STAGE CStructural heart disease

with prior or current

symptoms of HF

THERAPYGoals· Control symptoms· Patient education· Prevent hospitalization· Prevent mortality

Drugs for routine use· Diuretics for fluid retention· ACEI or ARB· Beta blockers· Aldosterone antagonists

Drugs for use in selected patients· Hydralazine/isosorbide dinitrate· ACEI and ARB· Digoxin

In selected patients· CRT· ICD· Revascularization or valvular

surgery as appropriate

STAGE DRefractory HF

THERAPY

Goals

· Prevent HF symptoms

· Prevent further cardiac

remodeling

Drugs

· ACEI or ARB as

appropriate

· Beta blockers as

appropriate

In selected patients

· ICD

· Revascularization or

valvular surgery as

appropriate

e.g., Patients with:

· Known structural heart disease and

· HF signs and symptoms

HFpEF HFrEF

THERAPY

Goals

· Heart healthy lifestyle

· Prevent vascular,

coronary disease

· Prevent LV structural

abnormalities

Drugs

· ACEI or ARB in

appropriate patients for

vascular disease or DM

· Statins as appropriate

THERAPYGoals· Control symptoms· Improve HRQOL· Reduce hospital

readmissions· Establish patient’s end-

of-life goals

Options· Advanced care

measures· Heart transplant· Chronic inotropes· Temporary or permanent

MCS· Experimental surgery or

drugs· Palliative care and

hospice· ICD deactivation

Refractory symptoms of HF at rest, despite GDMT

At Risk for Heart Failure Heart Failure

e.g., Patients with:

· Marked HF symptoms at

rest

· Recurrent hospitalizations

despite GDMT

e.g., Patients with:

· Previous MI

· LV remodeling including

LVH and low EF

· Asymptomatic valvular

disease

e.g., Patients with:

· HTN

· Atherosclerotic disease

· DM

· Obesity

· Metabolic syndrome

or

Patients

· Using cardiotoxins

· With family history of

cardiomyopathy

Development of

symptoms of HFStructural heart

disease

Heart Failure and Diet

Associations of

Mediterranean and Dietary

Approaches to Stop

Hypertension (DASH)

Improve the

cardiovascular risk

factors

Mediterranean diet 1 year (The

PREDIMED Study)

Vitamins B, C and E,

coenzyme Q10, alpha-lipoic

acid, chromium, omega-3

polyunsaturated fatty acids,

L-carnitine, and quercetin

Antioxidants in diet Improve the cardiovascular

risk factors

Cardiovascular health in the American Heart Association 2020 goals, US

children aged 12 to 19 years, National Health and Nutrition Examination

Survey (NHANES) 2009-2010* (available data as of June 1, 2012). *Healthy

Diet Score reflects 2007-2008 NHANES data.

Go A S et al. Circulation. 2013;127:e6-e245

Copyright © American Heart Association, Inc. All rights reserved

MM Lima- Martinez et al. (2011)

Hipertension y riesgo cadiovascular 28

(80%)

Epicardial adipose tissue

Epicardial adipose tissue and heart

failure

Diet compounds

Volume

Prognosis and quality of life

Endocrine or paracrine function

Metabolic Activity

Oxidative Stress

Coronaries and myocardium

Epicardial adipose tissue and

coronary artery disease

Jin-Sun Park e tal. (2013) Atherosclerosis 226; 134 - 139

Necrotic core

Dense calcium

Fibrous

Fibrofatty

>3,5 mm

<3,5 mm

Epicardial adipose tissue volume and

ventricle function

Short-axis views. Compared to healthy controls (A1/2), patients with DCM and moderately (B1/2)

and severely (C1/2) reduced left ventricular ejection fraction showed equally diminished indexed

EAT mass.

Doesch et al. (2013) Obesity 23: E253

Heart Failure

• Develop important changes in body composition and the disease course is marked by periodic

episodes of clinical decompensation.

• An altered balance between catabolism and anabolism is known to contribute to disease

progression and the transition from non-wasted heart failure to cardiac cachexia.

Controls HF EF <55% p Value HF EF 35–55% HF EF <35% p Value

(n =321) (n = 60) (n = 43) (n =17)

Epicardial fat volume

(cm3) 114,5 ±98,5 83,5 ± 67,1

<0,04 96,0 ± 73,9 52,2 ± 29,7

<0,05

Total calcium score 522 ± 1,324 656 ± 889 0,59 765 ± 1,030 445 ± 508 0,36

Khawaja T. et al. (2011) Am J Cardiol;108:397– 401

Epicardial fat volume (EFV)

Khawaja T. et al (2011) Am J Cardiol 108:397– 401

Request and Offers

• Inclusion in

organized projects

related with diet

• Functional food

expertise

• Nutraceutical/Pharmac

eutical Enterprize

• Table diets expertise

• Chemical analyzers

• Inclusion in organized

projects for

preclinical assays

Cardiology group. Health Research

Institute. Santiago de Compostela

Head: José Ramón González Juanatey

Researchers

Plataforms (Proteomics, Microscopy,

Luminex, Image)

Enterprise?

Students

Clinical Staff

Expertise

Three human cardiovascular systems:

• Cardiomyocytes

• Endothelial cells

• Epicardial adipose tissue cells

Animal models

For testing the effect of nutraceutical, chemical

products, diet compunds on metabolic function of the

cardiovascular systems.

Cardiology group. Health Research

Institute

Head: José Ramón González Juanatey

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