Nishant Shah, MD Duke University

1. Cardiometabolic Revolution:
Comprehensive Metabolic Care
In Heart Failure
Nishant Shah, MD
Assistant Professor of Medicine in Cardiology
Duke Heart Center
Duke School of Medicine
Duke Clinical Research Institute
@Nishant_ShahMD

2. Disclosures
• Consulting: Novartis, Amgen, Amarin, Merck
• Research Support: NIH, Amgen, Novartis, Janssen

3. Objectives
• Understand the spectrum of cardiometabolic disease and current
management guidelines
• Understand the cardiovascular benefits of SGLT2i and GLP1-RA
• Discuss current gaps in care in cardiometabolic disease
• Understand team based approaches to optimal cardiometabolic risk

4. What is Cardiometabolic Disease?
Dyslipidemia
Obesity Hyperglycemic Diseases
Fatty Liver Disease
Hypertension Chronic Kidney Disease
Spectrum of
interrelated
conditions

5. Hypertension
Clinic HBPM Day ABPM Night ABPM 24-hr ABPM
130/80 130/80 130/80 110/65 125/75
140/90 135/85 135/85 120/70 130/80
Stage 1 HTN
Stage 2 HTN
Out of office BP
measurements
are recommended
for confirmation
and med titration
Class 1, LOE A
Arnett DK, Blumenthal RS, Albert MA, et al. JACC 2019

6. Dyslipidemia
5-7.5%
Borderline
7.5-20%
Intermediate
>20%
High
<5%
Low
Monitor
Identify Risk
Enhancers
Identify Risk
Enhancers ±
LLT
LLT
Emphasize Heart Healthy Lifestyle Modifications
Primary Prevention
*LLT: Lipid lowering therapy
ACC/AHA PCE
10 year ASCVD
risk estimate
Recommendations
Assumes no prior CV event, no diagnosis of Diabetes, LDL <190mg/dL AND between ages of 45-75
Arnett DK, Blumenthal RS, Albert MA, et al. JACC 2019

7. Arnett DK, Blumenthal RS, Albert MA, et al. JACC 2019
• Fam hx of premature ASCVD
• Persistently elevated LDL ≥ 160 mg/dL
• Ethnicity (South Asians)
• CKD
• Metabolic syndrome
• Hx of Pre-eclampsia
• Hx of Premature menopause
• Inflammatory diseases
• HS-CRP ≥ 2.0 mg/dL
• Triglycerides ≥ 175 mg/dL,
• Lp(a) >50 mg/dL
• Apo B ≥130 mg/dL
• ABI < 0.9
Personal
Characteristics
Co-morbidities
Markers
Traditional risk
factors may only be
the tip of the iceberg
There may be more
than what meets the
eye
Risk Enhancers to Keep in Mind

8. • Multiple Events
• Age greater than 65
• FH
• DM
• HTN
• CKD
• Current Smoking
• Persistently elevated LDL
despite therapy
• Hx of congestive heart
failure
Very high risk factors
At the minimum:
LDL-C < 70mg/dL
However, lower is
better!!!
Secondary Prevention
Arnett DK, Blumenthal RS, Albert MA, et al. JACC 2019

9. • Targets lower LDL-C
goals in ASCVD
patients at higher risk
• Consistent with
endocrine guidelines
in patients with
diabetes
• Also consistent with
European guidelines
2022 Expert
Consensus
Decision Pathway
Aim for:
LDL-C < 55mg/dL
In high risk ASCVD!
This includes HF!!!
• Use of combination therapy
with statin to bring your LDL-
C down:
 Ezetimibe
 mAb PCSK9i
 Bempedoic Acid
 Inclisiran
Lloyd-Jones DM, Morris PB, et al. JACC 202

10. Diabetes is our problem too!
Age-adjusted prevalence of diabetes in 2010 Percent change in prevalence of diabetes from 1995-2010
www.CDC.gov

11. • Dietary counseling and heart
healthy diet
• At least 150 min of
moderate/vigorous physical
activity per week
• Aggressive treatment of
modifiable CV risk factors
• Consideration of metformin
upfront
If CV risk factors or Hb A1c not
controlled, strong
consideration should be made
for SGLT2i and/or GLP1-RA
Arnett DK, Blumenthal RS, Albert MA, et al. JACC 2019

12. SGLT2i vs GLP1-RA
Sodium Glucose Co-transporter 2
Inhibitor (SGLT2i)
• Patients with type 2 DM
I. EMPA REG OUTCOMES: ↓MACE, ↓HHF, ↓All cause Death
II. CANVAS: ↓MACE, ↓CV Death or HHF
III. DECLARE-TIMI 58: ↓CV Death or HHF
IV. SOLOIST-WHF: ↓CV Death, ↓HHF, ↓Urgent HF visit
• HF Patients without type 2 DM
I. DAPA-HF: ↓CV death and HHF
II. EMPEROR Reduced: ↓CV death and HHF
III. EMPEROR Preserved: ↓CV death and HHF
IV. DELIVER: ↓CV death and worsening HF
• Patients with CKD
I. CREDENCE: ↓ESRD, ↓worsening sCR, ↓ renal death, ↓ CV death
II. DAPA-CKD: ↓worsening eGFR, ↓renal death, ↓CV death, ↓ESRD
III. EMPA-Kidney: ↓worsening eGFR, ↓renal death, ↓CV death, ↓ESRD,
↓hospitalization
• Patients post MI
I. EMPACT MI: No difference in primary endpoint; ↓HHF
II. DAPA MI: No difference in MACE or HHF
Glucagon Like Peptide 1 Receptor
Agonist (GLP1-RA)
• Patients with type 2 DM
I. LEADER: ↓MACE
II. SUSTAIN 6: ↓MACE
III. Harmony Outcomes: ↓MACE, ↓HHF
IV. REWIND: ↓MACE: ↓Worsening renal function
V. Amplitude O: ↓MACE, ↓HHF
• Patients with HFpEF
• STEP-HFpEF: Improved QOL and functional status, ↓NT-ProBNP
Consider these therapies
Cardiovascular Drugs!
Many with HF may benefit from both agents

13. Change in Obesity Management Paradigm
Semaglutide 2.4mg once weekly in addition to lifestyle interventions in overweight or obese patients WITHOUT diabetes vs placebo
Step1 trial
Wilding et al. NEJM 2021; 384: 989

14. SURMOUNT1 Trial
AM Jastreboff et al. N Engl J Med 2022;387:205-216.
• Compared the dual glucose-
dependent insulinotropic
polypeptide and GLP1-RA
Tirzepatide
• 2539 adults
• BMI ≥30 OR BMI ≥27 with one
obesity related complication
excluding diabetes

15. SELECT Trial
• Multicentered, double blind, randomized placebo controlled, event
driven superiority trial of Semaglutide 2.4 mg vs placebo
• A total of 17,604 patients with established CVD, BMI of ≥ 27, and with
no diagnosis of DM were enrolled (8803 in Semaglutide arm and 8801 in
placebo arm
• The primary endpoint was a composite of death from cardiovascular
cause, nonfatal MI, or nonfatal stroke
• Semaglutide was superior to placebo in reducing incidence CV death,
nonfatal MI, and nonfatal stroke during a mean follow up of
approximately 40 months
• Semaglutide 2.4mg had a reduction in mean body weight of 9.4% vs
0.9% in the placebo arm by week 104.
AM Lincoff et al. N Engl J Med 2023;389:2221-2232.

16. Harmony Outcomes
• Multicentered, double blind, randomized placebo controlled, cardiovascular outcomes trial of albiglutide vs placebo in
patients CVD and type 2 DM
Hernandez AF et al. Lancet 2018.
Significant reduction in MACE No major difference in body weight

17. Barriers to Implementation
• Lack of insurance coverage
• Drug costs
• Provider inertia: lack of familiarity, time constraints, limited
resources
• Medical misinformation that impacts the patient’s trust in us
System wide changes are needed

18. It takes a team!
Julie Marshal, PA-C
5th Floor South Durham
Michelle Kelsey, MD
Cardiometabolic Clinic
Julius Wilder, MD
Michelle Ponder, MD John Guyton, MD Cara Hoke, MD
Endocrinology Cardiology

19. Conclusions
• Cardiometabolic disease includes a spectrum of CV risk factors
• Several guideline based approaches exist to modify cardiometabolic risk
• Aim for lower LDL-C threshold in ASCVD patients with HF
• Consider SGLT2i and GLP1-RA as cardiovascular drugs with tremendous HF
benefits
• Working as a team will allow us to better implement evidence based
preventative therapies

20. Thank you!
nishant.shah@duke.edu
@Nishant_ShahMD