nuevos parametros de tratamiento para heart failure.

1. HEART FAILURE :WHAT IS NEW

2. Definition
• HF is a complex clinical syndrome that results
from any structural or functional impairment
of ventricular filling or ejection of blood.

3. Epidemiology
• The lifetime risk of developing HF is 20% at 40 years of age.
• HF incidence: >650 000 new HF cases diagnosed annually
• HF incidence increases with age, rising from approximately 20
per 1000 individuals 65 to 69 years of age to >80 per 1000
individuals among those >85 years of age.
• Mortality rates for HF remain approximately 50% within 5
years of diagnosis

4. 1. Mozaffarian D et al. Circulation. 2015;131(4):e29-e322.
2. Mosterd A et al. Heart. 2007;93(9):1137-1146.
3. http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/Chronic-Conditions/Downloads/2012Chartbook.pdf
4. Cowie MR et al. Oxford PharmaGenesis; 2014. http://www.oxfordhealthpolicyforum.org/AHFreport. Accessed February 18, 2015.
5. Fauci AS et al. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008.
6. Cook C et al. Int J Cardiol. 2014;171(3):368-376.
NUMBER of PATIENTS
21 MILLION adults worldwide are
living with heart failure
This number is expected to
rise.1,2
REHOSPITALISATION
Heart failure is the NUMBER 1
cause of hospitalisation for
patients aged >65 years.4
MORTALITY
50% of heart failure patients die
within 5 years from diagnosis.5
COMORBIDITIES: The vast
majority of HF patients has 3 or
more comorbidities 3
ECONOMIC BURDEN
In 2012, the overall worldwide
cost of heart failure was nearly
$108 BILLION.6
The burden of heart failure

5. Classification

6. Overview of HF staging system
High Risk for Developing HF
Hypertension
CAD
Diabetes mellitus
Family history of cardiomyopathy
Asymptomatic HF
Previous MI
LV systolic dysfunction
Asymptomatic valvular disease
Symptomatic HF
Known structural heart disease
Shortness of breath and fatigue
Reduced exercise tolerance
Refractory
End-Stage HF
Marked symptoms at rest
despite maximal
medical therapy
A
B
C
D
Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.

7. PATHOGENESIS OF HF

8. HFpEF vs. HFrEF
HFpEF
Heart failure with
preserved ejection
fraction
“Diastolic HF”
HFrEF
Heart failure with
reduced ejection
fraction
“Systolic HF”
Left
ventricle
Left
ventricle

9. HFpEF vs. HFrEF
Poorly understood
Increasing in prevalence
No definitive treatments
High morbidity/mortality
Well studied
Decreasing in prevalence
Many proven treatments
Decreasing morbidity
Decreasing mortality

10. • Prevalence of HFpEF among patients with a discharge diagnosis of HF increased from
38% to 54% from 1987–20011
• Increasing prevalence of HFpEF may be a consequence of growing recognition,
population aging and increases in hypertension and obesity2
Patients
with
preserved
ejection
fraction
(%)
70
60
50
40
30
20
0
1986 1990 1994 1998 2002
r=0.92, p<0.001
1. Owan et al. N Engl J Med 2006;355:251–9
2. Blanche et al. Swiss Med Wkly 2010;140:66–72
Increasing HFpEF prevalence trends

11. In a retrospective study of 451 patients with HF in Sweden, time from diagnosis to first
post-diagnosis CV- or HF-related hospitalization was not significantly different between
HFpEF and HFrEF (p=0.49 and p=0.08, respectively)
Wikstrom et al. ESC 2011 Gothenburg,
Sweden, May 21–24, 2011
HFpEF & HFrEF: Similar initial hospital rates
Time to first CV hospitalization Time to first HF hospitalization
1.00
0.75
0.50
0.25
0
0 200 400 600 800 1,000
Time (days)
Survival
distribution
function
1.00
0.75
0.50
0.25
0
0 200 400 600 800 1,000
Time (days)
Survival
distribution
function
HFpEF (LVEF >45%)
HFrEF (LVEF ≤45%)
Wikstrom et al. ESC 2011 Gothenburg, Sweden, 21–24 May 2011

12. HFpEF survival rates are not improving
• Owan et al. N Engl J Med 2006;355:251–9
Patients with HFpEF (LVEF ≥50%)
Survival
1.0
0.8
0.6
0.4
0.2
0
0 1 2 3 4 5
Year
p=0.36
1987–1991
1992–1996
1997–2001
Survival
1.0
0.8
0.6
0.4
0.2
0
Patients with HFrEF (LVEF <50%)
0 1 2 3 4 5
Year
1987–1991
1992–1996
1997–2001
p=0.005

13. VENTRICULAR & ECM IN HFPEF

14. PATHOPHYSIOLOGY OF HFPEF

15. Microvascular inflammation
endothelium
interstitial fibrosis
cardiomyocyte
cardiomyocyte stiffening
Paulus. A Novel Paradigm for Heart Failure with Preserved Ejection Fraction. 2013; 62(4)

16. DISTENSIBILTY OF LV IN HFPEF

17. PATTERNS OF DPVR

18. CLINICAL FEATURES OF HF

22. The diagnosis of HFrEF requires three conditions to be satisfied
1. Symptoms typical of HF
2. Signs typical of HF
3. Reduced LVEF
The diagnosis of HFpEF requires four conditions to be satisfied
1. Symptoms typical of HF
2. Signs typical of HF
3. Normal or only mildly reduced LVEF and LV not dilated
4. Relevant structural heart disease (LV hypertrophy/LA enlargement) and/or
diastolic dysfunction
McMurray et al. Eur Heart J 2012;33:1787–847
The diagnosis of HFpEF is more difficult than the diagnosis of HFrEF
Diagnosing HF

23. MANAGEMENT

24. There are many treatment objectives for chronic HF
• Dickstein et al. Eur Heart J 2008;29:2388–442
• McMurray et al. Eur Heart J 2012;33:1787–847
Objectives of treatment for chronic HF
1. Prognosis • reduce mortality
2. Morbidity • relieve symptoms and signs
• improve QoL
• eliminate edema and fluid retention
• increase exercise capacity
• reduce fatigue and breathlessness
• reduce the need for hospitalization
• provide end of life care
3. Prevention • occurrence of myocardial damage
• progression of myocardial damage
• remodelling of the myocardium
• reoccurrence of symptoms and fluid
accumulation
• hospitalization

25. Landmark trials in patients with HFrEF
• Percentages are relative risk reductions vs comparator
• 1. SOLVD Investigators. N Engl J Med 1991;325:293–302
2. CIBIS-II Investigators. Lancet 1999;353:9–13; 3.
Granger et al. Lancet 2003;362:772−6
4. McMurray et al. Lancet 2003;362:767–771; 5.
Swedberg et al. Lancet 2010;376:875–85
6. Zannad et al. N Engl J Med 2011;364:11–21; 7.
McMurray et al. N Engl J Med 2014;371:993–1004
CIBIS-II2 (1999)
2,647 patients
Key benefits of bisoprolol (BB)
vs placebo:
• 34%  all-cause mortality
EMPHASIS-HF6 (2011)
2,737 patients
Key benefits of eplerenone
(MRA) vs placebo:
• 37%  CV mortality or
HF hospitalization
SHIFT5 (2010)
6,558 patients
Key benefits of ivabradine
(If inhibitor) vs placebo:
• 18%  CV death or HF
hospitalization
PARADIGM-HF7 (2014)
8,442 patients
Key benefits of LCZ696
(ARNI) vs enalapril:
• 20%  CV mortality or
HF hospitalization
SOLVD-T1 (1991)
2,569 patients
Key benefits of enalapril (ACEI)
vs placebo:
• 16%  all-cause mortality
CHARM-Alternative3
(2003)
2,028 patients
Key benefits of candesartan
(ARB) vs placebo:
• 23%  CV mortality or HF
hospitalization
CHARM-Added4 (2003)
2,548 patients
Key benefits of
candesartan (ARB) vs
placebo:
• 15%  CV mortality or HF
hospitalization
1990s 2000s 2010s

26. Chronic symptomatic systolic HF (NYHA II-IV) – Step 1
McMurray et al. Eur Heart J 2012;33:1787–847
Diuretics to relieve symptoms/signs of congestion
ACE inhibitor (or ARB if not tolerated)
+
ADD a beta-blocker
Still NYHA class
II-IV?
ADD an MR antagonist
YES NO
No further specific treatment
Continue in disease-management
programme
Treatment options for HFREF

27. Chronic symptomatic systolic HF (NYHA II-IV) – Step 2
McMurray et al. Eur Heart J 2012;33:1787–847
Still NYHA class II-IV?
YES NO
LVEF ≤ 35% ?
YES NO
SR and HR ≥ 70 beats/min
?
ADD ivabradine
Still NYHA class II-IV
and LVEF ≤ 35% ?
NO
YES
No further specific treatment
Continue in disease-management
programme
Treatment options for chronic HF

28. Chronic symptomatic systolic HF (NYHA II-IV) – Step 3
Still NYHA class II-IV and LVEF ≤35% ?
YES
NO
QRS duration ≥120 ms?
YES NO
Consider CRT-P/CRT-D Consider ICD
Stil NYHA class II-IV?
YES
Consider digoxin and/or H-ISDN
If end stage, consider LVAD and/or transplantation
No further specific treatment
Continue in disease-management
programme
NO
McMurray et al. Eur Heart J 2012;33:1787–847
Treatment options for chronic HF

29. MortalityinHFrEFremainshighdespitetheintroduction
oftherapiesthatimprovesurvival
• 1. McMurray et al. Eur Heart J 2012;33:1787–847;
• 2. SOLVD Investigators. N Engl J Med
1991;325:293–302; 3. CIBIS-II Investigators. Lancet
1999;353:9–13; 4. Pitt et al. N Engl J Med 1999;341:709-17;
5. Granger et al. Lancet 2003;362:772–66. 6. Go et al.
Circulation 2014;129:e28-e292; 7. Yancy et al. Circulation
2013;128:e240–327; 8. Levy et al. N Engl J Med
2002;347:1397–402
*On top of standard therapy at the time of study (except in CHARM-Alternative where background ACEI therapy was excluded). Patient populations varied between trials and as such relative risk
reductions cannot be directly compared. SOLVD (Studies of Left Ventricular Dysfunction), CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and RALES (Randomized Aldactone Evaluation Study) enrolled
chronic HF patients with LVEF≤35%. CHARM-Alternative (Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity) enrolled chronic HF patients with LVEF≤40%
Survival rates in chronic HF have improved with the introduction of new therapies1
 However, significant mortality remains – ~50% of patients die within 5 years of diagnosis6–8
16%
(4.5% ARR; mean
follow up of 41.4
months)
SOLVD1,2
34%
(5.5% ARR; mean
follow up
of 1.3 years)
CIBIS-II3
Reduction
in
relative
risk
of
mortality
vs
placebo
30%
(11.0% ARR; mean
follow up of 24
months)
RALES4
17%
(3.0% ARR; median
follow up of 33.7
months)
CHARM-
Alternative5
ACEI* β-blocker* MRA* ARB*

30. LCZ696 simultaneously inhibits neprilysin (via LBQ657)
and blocks AT1 receptors (via valsartan)
• Levin et al. N Engl J Med 1998;339:321–8
Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42
Schrier & Abraham. N Engl J Med 2009;341:577–85
Langenickel & Dole. Drug Discov Today: Ther Strateg 2012;9:e131–9
• Feng et al. Tetrahedron Letters 2012;53:275–6
Vasorelaxation
 Blood pressure
 Sympathetic tone
 Aldosterone levels
 Fibrosis
 Hypertrophy
 Natriuresis/diuresis
Inactive
fragments
ANP, BNP, CNP, other
vasoactive peptides*
AT1 receptor
Vasoconstriction
 Blood pressure
 Sympathetic tone
 Aldosterone
 Fibrosis
 Hypertrophy
Angiotensinogen
(liver secretion)
Ang I
Ang II
RAAS
LCZ696
Sacubitril
(AHU377; pro-drug)
Inhibiting
Enhancing
LBQ657
(NEP inhibitor)
OH
O
HN
O
HO
O
Valsartan
N
NH
N
N
N
O
OH
O

31. PARADIGM-HF: Study design
McMurray et al. Eur J Heart Fail 2013;15:1062–73
McMurray et al. Eur J Heart Fail 2014;16:817–25
McMurray et al. N Engl J Med 2014;371:993–1004
LCZ696
200 mg BID§
Randomization
n=8442
2 Weeks 1–2 Weeks 2–4 Weeks
Single-blind active
run-in period
Double-blind
Treatment period
On top of standard HFrEF therapy (excluding ACEIs and ARBs)
Median of 27 months’ follow-up
LCZ696
100 mg BID‡
Enalapril
10 mg BID*
Enalapril 10 mg BID#
LCZ696 200 mg BID§
.
For more details on the PARADIGM-HF study, refer to the dedicated slide kit

32. Primary endpoint: Death from CV
causes or first hospitalization for HF
• McMurray et al. N Engl J Med 2014;371:993–1004
Hazard ratio = 0.80 (95% CI: 0.73–0.87)
p<0.001
Days since randomization
No at risk
LCZ696 4,187 3,922 3,663 3,018 2,257 1,544 896 249
Enalapril 4,212 3,883 3,579 2,922 2,123 1,488 853 236
Cumulative
probability
1.0
0.6
0.4
0.2
0
0 180 360 540 720 900 1,080 1,260
Enalapril
LCZ696

33. Primary outcome
*Calculated with the use of stratified cox proportional-hazard models; ‡Two-sided p-values calculated by means of a stratified log-rank test without adjustment for multiple comparisons.
McMurray et al. N Engl J Med 2014;371:993–1004
Outcome, n %
LCZ696
(n=4,187)
Enalapril
(n=4,212)
Hazard ratio*
(95% CI) p value‡
Primary composite outcome
Death from CV causes or first
hospitalization for worsening of HF
914 (21.8) 1,117 (26.5) 0.80 (0.73–0.87) <0.001
Death from CV causes 558 (13.3) 693 (16.5) 0.80 (0.71–0.89) <0.001
First hospitalization for worsening
of HF
537 (12.8) 658 (15.6) 0.79 (0.71–0.89) <0.001
 The difference in favor of LCZ696 was seen early in the trial and at each interim analysis
 Over the duration of the trial, the numbers of patients who would need to have been treated
(NNT) to prevent:
• one primary event was 21 patients, and
• one death from CV causes was 32 patients

34. Prospectively defined safety events
• McMurray et al. N Engl J Med 2014;371:993–1004
• Fewer patients in the LCZ696 group than in the enalapril group stopped their study
medication because of an AE (10.7 vs 12.3%, p=0.03)
Event, n (%)
LCZ696
(n=4,187)
Enalapril
(n=4,212) p value
Hypotension
Symptomatic 588 (14.0) 388 (9.2) <0.001
Symptomatic with SBP <90 mmHg 112 (2.7) 59 (1.4) <0.001
Elevated serum creatinine
≥2.5 mg/dL 139 (3.3) 188 (4.5) 0.007
≥3.0 mg/dL 63 (1.5) 83 (2.0) 0.10
Elevated serum potassium
>5.5 mmol/L 674 (16.1) 727 (17.3) 0.15
>6.0 mmol/L 181 (4.3) 236 (5.6) 0.007
Cough 474 (11.3) 601 (14.3) <0.001
Angioedema (adjudicated by a blinded expert committee)
No treatment or use of antihistamines only 10 (0.2) 5 (0.1) 0.19
Catecholamines or glucocorticoids without hospitalization 6 (0.1) 4 (0.1) 0.52
Hospitalized without airway compromise 3 (0.1) 1 (<0.1) 0.31
Airway compromise 0 0 ---

36. Patients with HFpEF may require novel approaches
to treatment
1. McMurray et al. Eur Heart J 2012;33:1787–847
2. Blanche et al. Swiss Med Wkly 2010;140:66–72
HFrEF1
• Multiple, randomized controlled,
double-blinded, clinical trials
• Therapeutic strategies based on
outcomes
• General consensus on treatment
among the HF community
• Randomized controlled trials have
been supported by observational
data
• Evidence-based medicine
HFpEF1,2
• Mostly mechanistic studies and
small, non-definitive trials
• Therapeutic strategies based on
symptoms and co-morbidities
• Limited consensus on treatment
among the HF community
• Disconnect between randomized
controlled trials and
observational data
• Anecdote-based medicine

37. Thereis a needfor therapeuticadvances
in patientswith HFpEF
Pre-1980 1985 1990 1995 2000 2005 2010 2015
CCB‡§
(verapamil,
diltiazem)
Digoxin‡
Loop diuretics (e.g.
furosemide, bumetanide)
Beta-blocker‡
(bisoprolol)
There are few approved treatments recommended for the management of signs and symptoms of HFpEF6*
 While recent advances in the management of HFrEF have resulted in a significant
extension of life expectancy,1–5 this is not reflected in HFpEF6
 No proven therapies exist for the treatment of HFpEF6 and little progress has been
made towards identifying a suitable treatment in the last 30 years
1. Dickstein et al. Eur Heart J 2008;29:2388–442; 2. SOLVD Investigators. N Engl J Med
1991;325:293–302; 3. Granger et al. Lancet 2003;362:772–6; 4. Pitt et al. N Engl J Med
2003;348:1309–21; 5. Zannad et al. N Engl J Med 2011;364:11–21; 6. McMurray et al. Eur
Heart J 2012;33:1787–847

38. SGLT2 INHIBITORS:THE LATEST BREAKTHROUGH

39. Remaining glucose
is reabsorbed by
SGLT-1 (10%)
Glucose
filtration
SGLT-2
Glucose
SGLT-2 inhibitor
Sodium
ATPase, adenosine triphosphatase; HbA1c, glycated hemoglobin; MOA, mechanism of action; SBP, systolic blood pressure;
SGLT-1/2, sodium–glucose co-transporter-1/2
1. Marsenic O. Am J Kidney Dis 2009;53:875–85; 2. FORXIGA. Summary of Product Characteristics 2019. Available at: https://www.medicines.org.uk/emc/product/2865/smpc (accessed May 2019);
3. Mudaliar S et al. Diabetes Care 2016;39:1115–22
Decrease in intracellular
sodium concentration
Proximal tubule
Reduced glucose and
sodium reabsorption SGLT-2
Increased urinary
excretion of excess
glucose
SGLT-2 inhibitors block SGLT-2 and
reduce glucose and Na+ reabsorption1–3
Based on this MOA, the
following occur3:
• Diuresis
• Natriuresis
• HbA1c reduction
• Weight loss
• SBP reduction

40. SGLT2i as a class have benefits on various Modifiable
CV risk factors
1. Diab Vasc Dis Res. 2015 Mar; 12(2): 90–100
2. Diabetes Care 2016;39:1108–1114
3. Heerspink HJ, et al. Circulation. 2016 Sep 6;134(10):752-72.
4. Tang H, et al. Diabetologia. 2016 Sep 15. [Epub ahead of print]
Potential
& Novel
pathways of
CV effects of
SGLT2i1
BP1
Arterial
stiffness1
HDL-C1
Triglycerides1
Uric Acid1
Magnesium4
Oxidative
stress1
SNS activity
(?) 1
Albuminuria 1
Weight1
Visceral
adiposity1
Glucose1
Insulin1
Mild Ketonemia
(Thrifty
Substrate
Hypothesis)2
Natriuresis/
Blood
Volume1,3
SNS: Sympathetic Nervous System

41. SGLT2i reducing HF Outcomes
Apart from diuretic action, what is the impact
of SGLT2i on HF ?

42. Hallow KM et al. Diabetes Obes Metab. 2017 Oct 12. doi: 10.1111/dom.13126.
• SGLT2-i agent ↓ses IF volume by 2-fold greater than blood volume
• Loop diuretic ↓ses IF volume by only 78% of reduction in blood volume
SGLT2-i agent Effect Loop Diuretic Effect
Day
Day
Day
Day

43. DAPA-HF

50. SGLT-2i in Established HF
• An Outcome Trifecta
• Reduces CV death
• Reduces hospitalizations for HF
• Improves symptom burden
• All with a favorable safety profile

51. Impact of SGLT2i CVOTs:
New Algorithm for Diabetes Treatment based on
CVD status
Rodriguez V, et al. J Clin Lipidol. 2017 Jul 22. pii: S1933-2874(17)30389-6.

52. Ongoing Trials Will Look to Confirm CV Benefits in Patients With
HF
2018 2019 2020 2021 2022
1Q 2Q 3Q 4Q 1Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q
Select
SGLT2i
HF
Trials
CV/HF
Outcomes
and/or
Biomarkers
2Q 3Q
DAPA-HF1
PRESERVED-HF7
EMPERIAL-Reduced8
HFrEF
DETERMINE-Reduced9
Exercise
Capacity
EMPERIAL-Preserved10
HFpEF
DETERMINE-Preserved11
HFrEF
HFpEF
EMPEROR-Reduced2
DEFINE-HF3
DELIVER5
EMPEROR-Preserved6
SOLOIST-WHF4
HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction.
1. ClinicalTrials.gov. DAPA-HF. NCT03036124. https://clinicaltrials.gov/ct2/show/record/NCT03036124. Accessed June 11, 2019. 2. ClinicalTrials.gov. EMPEROR-Reduced. NCT03057977. https://clinicaltrials.gov/ct2/show/NCT03057977. Accessed June 11, 2019.
3. ClinicalTrials.gov. DEFINE-HF. NCT02653482. https://clinicaltrials.gov/ct2/show/NCT02653482. Accessed June 11, 2019.4. ClinicalTrials.gov. SOLOIST-WHF. NCT03521934. https://clinicaltrials.gov/ct2/show/NCT03521934. Accessed June 24, 2019.5. ClinicalTrials.gov.
DELIVER. NCT03619213. https://clinicaltrials.gov/ct2/show/record/NCT03619213. Accessed June 11, 2019.6. ClinicalTrials.gov. EMPEROR-Preserved. NCT03057951. https://clinicaltrials.gov/ct2/show/NCT03057951.Accessed June 11, 2019.7. ClinicalTrials.gov.
PRESERVED-HF. NCT03030235. https://clinicaltrials.gov/ct2/show/NCT03030235. Accessed June 19, 2019.8. ClinicalTrials.gov. EMPERIAL-Reduced. NCT03448419. https://clinicaltrials.gov/ct2/show/record/NCT03448419. Accessed June 11, 2019.9. ClinicalTrials.gov.
DETERMINE-Reduced. NCT03877237.https://clinicaltrials.gov/ct2/show/NCT03877237. Accessed June 11, 2019.10. ClinicalTrials.gov. EMPERIAL-Preserved. NCT03448406. https://clinicaltrials.gov/ct2/show/record/NCT03448406. Accessed June 11, 2019.
11. ClinicalTrials.gov. DETERMINE-Preserved. NCT03877224. https://clinicaltrials.gov/ct2/show/NCT03877224. Accessed June 11, 2019

53. • SGLT-2i prevent symptomatic HF in high-risk patients
• SGLT-2i (dapagliflozin) reduce death, HF hospitalizations and
symptom burden in patients with established HFrEF
• Opens new era in HFrEF management – with new class of
disease-modifying agents
• Important implications for clinical practice and HF guidelines
• Efficacy in treatment of HFpEF remains to be established
SALIENT FEATURES OF SGLT2 INHIBITORS

54. Device Therapy for HF
• Implantable cardioverter-defibrillator
• Cardiac resynchronization therapy
• Mechanical Circulatory Support
• Cardiac Transplantation

55. Digoxin: recommendation
• Digoxin can be beneficial in patients with HFrEF,
to decrease hospitalizations for HF
• treatment with digoxin for 1 to 3 months can improve
symptoms, HRQOL (Health Related Quality of Life),
and exercise tolerance in patients with mild to
moderate HF
• treatment with digoxin for 2 to 5 years had no effect
on mortality but modestly reduced the combined
risk of death and hospitalization
• Digoxin can be used only in patients who remain
symptomatic despite therapy with the
neurohormonal antagonists or in patients with AF

56. Pulmonary Artery Pressure-Guided Therapy for
Ambulatory Heart Failure Patients in Clinical Practice:
1-Year Outcomes from the CardioMEMS Post-Approval Study
David M. Shavelle MD1, Akshay S. Desai MD, William T. Abraham MD, Robert
C. Bourge MD, Nirav Raval MD, Lisa D. Rathman NP, J. Thomas J. Heywood
MD, Rita A. Jermyn MD, Jamie Pelzel MD, Orvar T. Jonsson MD, Maria Rosa
Costanzo MD, John D. Henderson, Sandra A. Carey PhD,
Philip B. Adamson MD and Lynne W. Stevenson MD
for the CardioMEMS PAS Investigators
1Division of Cardiology, University of Southern California, Los Angeles, CA
Registration: www.clinicaltrials.gov, NCT 02279888

57. BACKGROUND
1Abraham WT
, et al. Lancet 2011:377:658-666.
• The burden of HF hospitalization (HFH) remains high despite
increasingly effective medical therapy
• Most HFH occur because of ‘congestion’ or elevated cardiac filling
pressures
• Increases in pulmonary artery (PA) pressures occur weeks in
advance of the signs and symptoms that prompt HFH
• Therapy guided by PA pressures in the randomized CHAMPION
study1 resulted in a 37% reduction in HFH rates and all cause
hospitalization (ACH)

58. Sensor Home electronics unit
Systolic PAP
Mean PAP
Diastolic PAP
PA pressure trend data
Daily PA measurement
CardioMEMS-HF system: Ambulatory Hemodynamic
Monitoring with an Implantable PAP Sensor
Database

59. Hospitalizations for HF
at 1 year
1.24
0.52
0.4
0.2
0
1-Year Pre Implant
0.8
0.6
1.2
1
1.4
HFH
Rate
(events/pt-yr)
1 Year Post-Implant
0.42 (0.38, 0.47)
p<0.0001
0.56 (0.51, 0.62)
p<0.0001
1.24
44%
0.69
0
0.2
0.4
0.6
0.8
1
1.2
1.4
HFH/Death
Rate
(events/pt-yr)
1-Year Pre Implant 1 Year Post-Implant
Hospitalizations for HF/Death at
1 year
Hazard Ratio, 95% Confidence Interval and p-value estimated from the Anderson-Gill model.
All hospitalization events adjudicated by CEC.
58%

60. All Cause Hospitalizations at 1 year
0
1-Year Pre Implant
1 Year Post-Implant
2.25
0.72 (0.67, 0.77)
p<0.0001
28%
1.61
0.5
1
1.5
2
2.5
All
Cause
Hospitalization
(events/pt-yr)
Hazard Ratio, 95% Confidence Interval and p-value estimated from the Anderson-Gill model.
All hospitalization events adjudicated by CEC.

61. Survivor Analysis: Hospitalizations for HF
at 1 year, n=1009 (Survival 84%)
0.4
0.2
0.0
1-Year Pre Implant
1 Year Post-Implant
1.20
0.41
0.8
0.6
1.2
1.0
1.4
0.34 (0.30, 0.39)
p<0.0001
66%
HFH
Rate
(events/pt-yr)
Hazard Ratio, 95% Confidence Interval and p-value estimated from the Anderson-Gill model.
All hospitalization events adjudicated by CEC.

62. • In the commercial setting, PA pressure-guided therapy for HF:
• Decreased PA pressures
• Decreased HF Hospitalizations
• Across sex and race
• Across all EF ranges
• Amongst 1-year survivors
• Decreased All-Cause Hospitalization
• PA pressure-guided therapy was safe with few device/system related
complications and a low rate of pressure sensor failure
CONCLUSIONS OF CHAMPION TRIAL

63. Promising Drugs In HF

64. An overview of the presented novel therapeutic methods with
respect to their mechanism of action and latest stage of
clinical development
Machaj et al,. New therapies for the treatment of heart failure: a summary of recent accomplishments. Therapeutics and

65. Summary & Conclusions
• Prevalence of HF is fast assuming epidemic proportions
as evident by growing number of hospitalizations,
increased mortality & spiraling costs associated with it.
• Prognosis remains dismal as mortality is higher than
many malignancies.
• Diagnosis of HF is clinical but classification requires
ECHO assessment
• HFpEF comprises 50% of total HF cases
• Treatment of HFrEF is well established with
ACEi/ARB/ARNI, MRA, Beta blockers providing
substantial mortality benefit.
•

66. Contd..
• Specific therapy for HFpEF is still a distant dream & treating
co-morbid conditions remains only option.
• Device therapy like ICD, CRT & IHM are beneficial come at
expense of prohibitive cost.
• Newer drugs continue to evolve to combat the deadly
disease. Omecamtiv mecarbil, Vericiguat, Rolophylline,
Istaroxime are few examples.
• SGLT2 inhibitor is the new hope to millions of HF patients with
DM.
• A time may come when SGLT2 inhibitors will be routinely
used in HF patients irrespective of diabetic status.