Lo mejor del Congreso ESC 2014 de Barcelona Jueves, 04 de Septiembre de 2014 De 19h a 20:30h http://esc2014.secardiologia.es Lo mejor sobre Insuficiencia Cardiaca Dr. Esteban López de Sá Hospital Universitario La Paz, Madrid https://twitter.com/elopezdesa

1. Lo mejor sobre Insuficiencia
Cardiaca
Dr. Esteban López de Sá
Unidad de Cuidados Agudos Cardiológicos.
Hospital Universitario La Paz. Madrid

2. Aspectos a tratar
• Diagnóstico
• Tratamiento no farmacológico
• Tratamiento farmacológico

3. Aspectos a tratar
• Diagnóstico
• Tratamiento no farmacológico
• Tratamiento farmacológico

4. A new wearable textile vest for
pulmonary congestion tracking in
acutely decompensated heart failure
patients: A pilot study
Cuba-Gyllensten I, Gastelurrutia P, Riistama J,
Zamora E, Llibre C, Caballero A, de Antonio M,
Aarts R, Lupon J, and Bayes-Genis A

5. Bio-impedance spectroscopy
R0 R∞

6. Improvements during therapy
• Relative changes in BI tracked fluid loss from weight changes
(p<0.001) and CSS changes (p<0.001)
• Significant correlations between BI and LVEF (r=0.450, p=0.047)
and NT-proBNP levels (r=−0.41, p=0.038).

7. Aspectos a tratar
• Diagnóstico
• Tratamiento no farmacológico
• Tratamiento farmacológico

8. Study Of Dietary Intervention Under 100
MMOL in Heart Failure
SODIUM-HF: A pilot study
Eloisa Colin-Ramirez BSc PhD, Finlay McAlister MD MSc, Yinggan Zheng
MA MEd, Sangita Sharma PhD, Paul Armstrong MD, Justin A Ezekowitz
MBBCh MSc
University of Alberta
Division of Cardiology, Department of Medicine

9. Study hypothesis
• Patients with HF following a low-sodium diet will
have a reduction in BNP levels and improvement in
quality of life when compared to patients following a
moderate-sodium diet.

10. Results: 6 month results
Low-sodium diet (n=18) Moderate-sodium diet (n=17)
Baseline 6 months
Values are medians (25th-75th percentiles)
P
value
Baseline 6 months
P
value
BNP, pg/mL
216 (25-670) 71 (39-222) 0.006 171 (100-558) 188 (69-410) 0.67
KCCQ clinical
summary score 62.8 (41.2-
72.4)
75.3 (61.5-
87.5)
0.006
66.4 (55.2-
77.1)
72.9 (67.7-
85.4)
0.07
KCCQ overall
summary score 59.6 (39.1-
73.2)
64.6 (50.3-
86.1)
0.04
65.5 (47.7-
82.3)
72.4 (63.8-
86.3)
0.07

11. Post-hoc analysis: BNP
Δ-1(-51, 14)
Δ-50 (-272, -10)

12. Autonomic Modulation Therapy
Vagal
96 Eligible Patients, Implanted
63 ON therapy 32 OFF therapy
Lost Paired Data (n=4)
Deceased (n=1)
Safety FU Only (n=2)
Lost to FU (n=1)
Lost Paired Data (n=4)
Deceased (n=2)
Safety FU Only (n=1)
No Echo Data (n=1)
59 Therapy
Patients with
paired data sets
28 Control
Patients with
paired data sets
Modified intention to treat analysis
1 Death
95 Randomized
Stimulation

13. Primary Endpoint—LVESD
4,9 4,9 5,2 5,1
7
6
5
4
3
2
1
0
Baseline 6 Months Baseline 6 Months
Therapy Control
LVESD (cm)

14. 11
Screening, Enrollment and Follow-up
Screening
n=78
Randomization
n=60
Right-Sided
Implantation
n=29
Titration
n=29
Inc / Exc failure (n=12)
Withdrawal (n=4)
Brady arrest (n=1)
Sudden death (n=1)
Left-Sided
Implantation
n=31
Titration
n=30
3-month F/U
n=29
3-month F/U
n=28
Death 1
n=1
Death 2
n=2
6-month F/U
n=29
6-month F/U
n=28
ANTHEM-HF Study
ANTHEM-HF
1. Embolic stroke (implant-related)
2. HF death (unrelated) and sudden death (unrelated)

15. ANTHEM-HF Study 15
Primary Efficacy Endpoints
- 1 5 - 1 0 - 5 0 5 1 0
P o o l e d
L e f t
R i g h t
P o o l e d
L e f t
R i g h t
LVESV (mL) LVEF (%)
Mean
ANTHEM-HF
Pooled: n=57; Left: n=28; Right: n=29 95% Confidence Interval

16. Aspectos a tratar
• Diagnóstico
• Tratamiento no farmacológico
• Tratamiento farmacológico

17. Effect of ferric carboxymaltose on
functional capacity in patients
with heart failure and iron deficiency
(CONFIRM-HF)
Piotr Ponikowski, Dirk J. van Veldhuisen, Josep Comin-Colet
Georg Ertl, Michel Komajda, Viacheslav Mareev
Theresa McDonagh, Alexander Parkhomenko, Luigi Tavazzi
Victoria Levesque, Claudio Mori, Bernard Roubert Gerasimos
Filippatos, Frank Ruschitzka, Stefan D. Anker
for the CONFIRM-HF Investigators.
Sponsor: Vifor Pharma Ltd.

18. CONFIRM-HF
• Design: Multicentre, randomised (1:1), double-blind, placebo-controlled
• Main inclusion criteria:
 NYHA class II / III, LVEF ≤45%
 BNP > 100 pg/mL or NT-proBNP > 400 pg/mL
 Iron deficiency: serum ferritin <100 ng/mL or 100-300 ng/mL if TSAT <20%
 Hb < 15 g/dL
• Blinding:
 Clinical staff: unblinded and blinded personnel
 Patients: usage of curtains and black syringes for injections
Correction phase
FCM up to 2000mg
(2 x 500-1000mg i.v.)
Maintenance phase
FCM treatment continues
if ID is not corrected
(500mg i.v.)
W36
Ferric Carboxymaltose (FCM)
Placebo
Screening
D0
1° EP:
6MWT
W6 W12 W24
Ponikowski P et al. ESC Heart Fail J 2014, in press

19. FCM improved 6MWT at week 24
FCM vs placebo: 33 ± 11 m (least squares mean ± SE)
P=0.002
20
10
0
-10
-20
-30
Week 24
LSM change in 6MWT distance
from baseline (m)
FCM (N=150)
Placebo (N=151)
30
Primary endpoint:
change in 6-minutes walking test distance at Week 24
Eur Heart J first published online August 31, 2014

20. PARADIGM-HF
Natriuretic Peptide System Renin Angiotensin System
pro-BNP
Neprilysin
Vasodilation
blood pressure
sympathetic tone
aldosterone levels
Fibrosis
hypertrophy
Natriuresis/Diuresis
Inactive
fragments
NT-pro BNP
X
Angiotensinogen
(liver secretion)
Angiotensin II
AT1 receptor
X
Vasoconstriction
blood pressure
sympathetic tone
aldosterone
fibrosis
hypertrophy
Heart Failure
O
NH
N
N
N
N
LCZ696
O
OH
O
OH HN O
HO O
Valsartan
AHU377
↓
LBQ657
BNP
Angiotensin I
LCZ696 A First-in-Class
Angiotensin Receptor
Neprilysin Inhibitor

21. PARADIGM-HF: Entry Criteria
• NYHA class II-IV heart failure
• LV ejection fraction ≤ 40%  35%
• BNP ≥ 150 (or NT-proBNP ≥ 600), but one-third lower
if hospitalized for heart failure within 12 months
• Any use of ACE inhibitor or ARB, but able to tolerate
stable dose equivalent to at least enalapril 10 mg daily
for at least 4 weeks
• Guideline-recommended use of beta-blockers and
mineralocorticoid receptor antagonists
• Systolic BP ≥ 95 mm Hg, eGFR ≥ 30 ml/min/1.73 m2
and serum K ≤ 5.4 mEq/L at randomization

22. PARADIGM-HF: Study Design

23. PARADIGM-HF: Patient Disposition
10,521 patients screened at
1043 centers in 47 countries
Did not fulfill criteria
for randomization
(n=2079)
Randomized erroneously
or at sites closed due to
GCP violations (n=43)
8399 patients randomized for ITT analysis
LCZ696 (n=4187)
At last visit
375 mg daily
11 lost to follow-up
Enalapril (n=4212)
At last visit
18.9 mg daily
9 lost to follow-up
median 27 months
of follow-up

24. PARADIGM-HF: CV Death or HF
Hospitalization (Primary Endpoint)
40
32
24
16
8
0
Enalapril
(n=4212)
360 540 720 900 1080 1260
Days After Randomization
0 180
Patients at Risk
1117
Kaplan-Meier Estimate of
Cumulative Rates (%)
914
LCZ696
(n=4187)
HR = 0.80 (0.73-0.87)
P = 0.0000002
Number needed to treat = 21
LCZ696 4187 3922 3663 3018 2257 1544 896 249
Enalapril 4212 3883 3579 2922 2123 1488 853 236

25. PARADIGM-HF:
Effect of LCZ696 vs Enalapril on Primary
Endpoint and Its Components
LCZ696
(n=4187)
Enalapril
(n=4212)
HR
(95% CI)
P
Value
Primary
endpoint
914
(21.8%)
1117
(26.5%)
0.80
(0.73-0.87)
0.0000002
Cardiovascular
death
558
(13.3%)
693
(16.5%)
0.80
(0.71-0.89)
0.00004
Hospitalization
for heart failure
537
(12.8%)
658
(15.6%)
0.79
(0.71- 0.89)
0.00004

26. Angiotensin Neprilysin Inhibition With LCZ696
Doubles Effect on CV Death of Current
10%
Inhibitors of the RAS
20%
20%
30%
40%
ACE
inhibitor
Angiotensin
receptor
blocker
0%
% Decrease in Mortality
18%
Angiotensin
neprilysin
inhibition
15%