Presentación realizada por el Dr. José Manuel García Pinilla en el directo online ‘Lo mejor del Congreso ACC Orlando 2018’, celebrado en la SEC el 13 de marzo de 2018

1. Lo mejor del Congreso ACC Orlando 2018
LO MEJOR EN INSUFICIENCIA
CARDIACA
JOSÉ MANUEL GARCÍA PINILLA
UNIDAD DE INSUFICIENCIA CARDIACA Y CARDIOPATÍAS
FAMILIARES
A.G.C. DE CARDIOLOGÍA Y CIRUGÍA CARDIOVASCULAR
H. UNIVERSITARIO VIRGEN DE LA VICTORIA
MÁLAGA

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3. Lo mejor del Congreso ACC Orlando 2018
Study Design
.
Short Term (ST) Cohort1
N=294
6-month follow-up
Randomization
1:1
Patient meets MOMENTUM 3
eligibility criteria?
Long Term (LT) Cohort
N=366
2-year follow-up
Additional 72 patients
enrolled
HeartMate 3 Pump
N=190
HeartMate II Pump
N=176
Withdrawn before implant
N = 4
No LVAD implant: 1
Withdrawal of consent: 1
Transplant: 1
Implanted with non-study
LVAD: 1
Withdrawn before implant
N = 1
Death: 1
Implanted with
HeartMate 3
N=189
Implanted with
HeartMate II
N=172
Intent-to-Treat (ITT) Population
N=366
Per Protocol Population
N=361
Full Cohort
N=1028
2-year follow-up
1Mehra et al. A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure. N Engl J Med 2017;376(5):440-50.
7
• SUPERVIVENCIA A LOS DOS AÑOS LIBRE DE ICTUS O
REINTERVENCIÓN PARA REEMPLAZAR O RETIRAR UN
SISTEMA MALFUNCIONANTE

4. Lo mejor del Congreso ACC Orlando 2018
Primary Endpoint Component 1
Overall Survival
No. at Risk
HeartMate 3
HeartMate II
HeartMate 3
HeartMate II
HR denotes hazard ratio; CI, confidence interval
12
Primary Endpoint Component 2
Freedom from Disabling Stroke
No. at Risk
HeartMate 3
HeartMate II
HeartMate II
HeartMate 3
HR denotes hazard ratio; CI, confidence interval
13

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6. Lo mejor del Congreso ACC Orlando 2018

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Subgroup Analyses of the Primary Endpoint (ITT)
denotes bridge to transplant; BTC, bridge to candidacy; DT, destination therapy
Favors
HeartMate 3
Favors
HeartMate II

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CONCLUSIONES
• HM3 fue clínicamente superior a HM2 en el
seguimiento a largo plazo (2 años)
• El beneficio se debió a una menor tasa de
reintervención con HM3 (exceso de
malfuncionamiento por trombosis del dispositivo
HM2)
• La tasa de ictus fue inferior con HM3
• HM3 sería especialmente útil en pacientes que
deben esperar mucho tiempo en lista para TxC o
que reciben asistencia como terapia de destino

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Barry A. Borlaug
On behalf of the
NHLBI Heart Failure Clinical Research Network
A Randomized Clinical Trial
Inorganic Nitrite Delivery to Improve
Exercise Capacity in HFpEF
INDIE-HFpEF
Inorganic Nitrite: Novel NO providing therapy
Lundberg et al. Nat Rev Drug Disc 2008
Background

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Hypothesis
• As compared to placebo, 4 weeks treatment with
inhaled, nebulized inorganic nitrite will improve
peak exercise capacity in HFpEF patients as
assessed by cardiopulmonary exercise testing
(CPET).
Study population
•NYHA class II-IV H Fsymptoms +EF≥ 50%
•Objective evidence of HF (at least one)
HF hospitalization
Elevated NT-proBNP or BNP
Elevated rest or exercise PAWP at RHC
Echo Doppler DD + Loop diuretic
•Reduced exercise capacity (peak VO2≥75%)
•Identify HF symptoms as the primary factor
limiting ability to be active on questionnaire
Versus neurologic, orthopedic or life-style factors

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Study Design: Randomized, double-blind,
placebo-controlled crossover study
Nitrite – 4 weeks
4 weeks
No drug
2 weeks
Placebo – 4 weeks
4 weeks
No drug
2 weeks
80 mg if tolerated46mg
80 mg if tolerated46mg
Placebo – 4 weeks
4 weeks
No drug
2 weeks
Nitrite – 4 weeks
4 weeks
No drug
2 weeks
80 mg if tolerated46mg
80 mg if tolerated46mg
Visit 2:
CPET,
Secondary
Endpoints
Visit 3:
CPET
Secondary
Endpoints
Single-
Dose
Run In
Visit 1:
Baseline
evaluations +
Screening
CPET
Yes
No Run In Fail
Randomize
Patient
Tolerates
Run In?

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INDIE Primary End-point
• Peak oxygen consumption (Peak VO2) during
cardiopulmonary exercise testing
p=0.27
PeakVO2(ml/min/kg)
-5
0
5
10
15
20
Placebo Inorganic Nitrite Treatment Difference
Primary Endpoint
CONCLUSIÓN: Los nitritos inorgánicos inhalados no mejoraron
la capacidad funcional (medida por VO2 max), la calidad de vida
ni los niveles de Nt-proBNP

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Carvedilol for PrEvention of Chemotherapy-Induced CardiotoxicitY
Results of the Prospective, Randomized, Double Blind, Placebo-Controlled
CECCY Trial
Mônica Samuel Avila M.D., Silvia Moreira Ayub-Ferreira M.D. P.h.D., Edimar Alcides Bocchi M.D. P.h.D
On behalf of all CECCY trial Investigators
@monicaAGrinberg
ClinicalTrials.gov Identifier: NCT01724450
No disclosures to declare

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CECCY Trial
Anthracycline Infusion
3 weeks 3 weeks3 weeks3 weeks
Weekly Taxane Infusion
Carvedilol/Placebo Treatment (20 weeks)
Physical Exam
Biomarkers
Randomization
Clinical Status, Biomarkers and Image Evaluations
12 weeks6 weeks
Chemotherapy Treatment
24 weeks
Echocardiography
End of
Evaluation
Physical Exam
Biomarkers
Physical Exam
Biomarkers
Echocardiography
Physical Exam
Biomarkers
Physical Exam
Biomarkers
Echocardiography
Physical Exam
Biomarkers
Echocardiography
3 weeks 9 weeks
Study Design
• Chemotherapy Treatment: doxorubicin + cyclophosphamide and paclitaxel
• Cumulative ANT (doxorubicin) dose: 240 mg/m2

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n= 96 + 96

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CECCY Trial
14%
86%
Placebo
no.pts withdecreaseofLVEF≥ 10%
no. pts with decrease of LVEF < 10%
15%
85%
Carvedilol
no.pts withdecreaseofLVEF≥ 10%
no. pts with decrease of LVEF < 10%
Results - Primary Endpoint
p=ns

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Percentage of patients at the different dose
ranges of carvedilol or placebo.
Dose of drug (mg/day) Carvedilol (n=96) Placebo (n=96)
6.25 mg/day – no. of patients (%) 21 (21.8) 24 (25.0)
12.5 mg/day – no. of patients (%) 33 (34.3) 19 (19.7)
25 mg/day – no. of patients (%) 27 (28.1) 32 (33.3)
50 mg/day – no. of patients (%) 9 (9.3) 18 (18.7)
Secondary Endpoints - BNP

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Seguimiento corto (sólo 6 meses)
Estudio monocéntrico
La incidencia de cardiotoxicidad con dosis contemporáneas
de antraciclinas fue menor que la esperada con dosis
moderadas-altas
El tratamiento con carvedilol no tuvo impacto sobre la
función ventricular a 6 meses
Carvedilol
Redujo la elevación de TnI
Redujo el % de pacientes con disfunción diastólica
Obejtivó una tendencia a una menor elevación del
LVDD

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Lisinopril or Carvedilol for Prevention of
Trastuzumab Induced Cardiotoxicity

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Definition of Cardiotoxicity
• LVEFdecreasefrom thebaselineof≥10%
or
• LVEFdecreasefrom thebaselineof≥5% to<50%
• With or without symptoms of HF
• The measurement of LVEF was made locally at
each site at baseline, 3, 6, 9, and 12 months.• OBJETIVO PRIMARIO
– La administración de lisinopril o carvedilol reduce la cardiotoxicidad
en comparación con placebo
• OBJETIVOS SECUNDARIOS
– Establecer si el efecto es consistente en asociación o no a
antraciclinas
– Determinar si la administración de lisinopril o carvedilol da lugar a
menos interrupciones de tratamiento con Trastuzumab

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2 años de seguimiento (1 en tratamiento con trastuzumab)

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Cardiotoxicity-free survival for the cohort with
Trastuzumab + Anthracycline
Probability of
Cardiotoxicity
Carvedilol
HR 0.49
95% CI (0.27, 0.89)
P=0.009
Lisinopril
HR 0.53
95% CI (0.30, 0.94)
P=0.015
Cardiotoxicity-free survival for the cohort with
Trastuzumab only
Probability of
Cardiotoxicity
Carvedilol
HR 1.05
95% CI (0.57, 1.93)
P=0.56
Lisinopril
HR 1.17
95% CI (0.62, 2.20)
P=0.59

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Presenter: Ambarish Pandey
UT Southwestern Center Dallas, TX
Hospital Performance Based on 30-Day Risk
Standardized Mortality and Long-Term Survival after
Heart Failure : An Analysis of the GWTG-HF Registry
@ambarish4786
Co-authors: K Patel, L Liang, A DeVore, D Bhatt, C Yancy, A Hernandez, P Heidenreich,
J de Lemos, G Fonarow
Study Objective
Evaluate the association between hospital performance
based on 30-day risk standardized mortality rate & long-
term survival patients hospitalized with acute HF at GWTG-
HF participating centers

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Long-term Outcomes
Q1
High Performing
Q2 Q3
Q4
Low Performing
Overall Population
Median Survival, days
(95% CI)
717
(700 – 734)
685
(668 – 705)
654
(636 – 674)
579
(565 – 594)
5-year Mortality (%) 75.6 76.2 76.9 79.6
30-day Survivors
Median Survival, days
(95% CI)
832
(815 – 852)
825
(805 – 843)
814
(794 – 831)
759
(742 – 779)
5-year Mortality (%) 73.7 73.7 74.3 76.8
Hospital Performance by 30-day RSMR and
Long-term Survival
30-day SurvivorsOverall Population
Q2
Q3
Q1 (High Performing)
Q4 (Low Performing)
Hazard RatioLower risk Higher risk Hazard RatioLower risk Higher risk
Adjusted for patient- and hospital-level covariates
22%≥ Risk
Adjusted Association of Hospital Performance
by 30-day RSMR with 5-y Mortality

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Ferric Iron in Heart Failure (FERRIC-HF) II
Randomized Controlled Trial of the Effect of
Iron Isomaltoside on Skeletal Muscle
Energetics in Iron Deficient Patients
with Chronic Heart Failure
Darlington Obinnaya Okonko, BSc,MBBS,PhD
Ferric-HF II

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Lower MortalityandHeart FailureHospitalizationFollowing
Implant of anAmbulatoryHemodynamicSensor
JacobAbraham, MD, Orvar Jonsson, MD, Guilherme H. Oliveira, MD,
Andre Artis, MD, Ali Valika, MD, Robert Capodilupo, MD, Phillip B.
Adamson, MD, Gregory Roberts, BS, Nirav Dalal, MS MBA, Rupinder
Bharmi, MS, Akshay S. Desai, MD, MPH, Raymond L. Benza, MD
Providence Heart Institute
Patient Selection
N=1351patientswithsensor
N=1289
N=1181
N=1176
N = 62, Discontinuous enrollment
N = 108, HMO insurance
N = 5, Pre-index LVAD

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Lower MortalityandHeart FailureHospitalizationFollowing
Implant of anAmbulatoryHemodynamicSensor
JacobAbraham, MD, Orvar Jonsson, MD, Guilherme H. Oliveira, MD,
Andre Artis, MD, Ali Valika, MD, Robert Capodilupo, MD, Phillip B.
Adamson, MD, Gregory Roberts, BS, Nirav Dalal, MS MBA, Rupinder
Bharmi, MS, Akshay S. Desai, MD, MPH, Raymond L. Benza, MD
Providence Heart Institute
Methods
Objective: Evaluate the effectiveness of hemodynamic monitoring on reducing mortality and HFH in general
population
Studydesign: Retrospective cohort study based on administrative claims using 100% data from the CMS Standard
Analytic File
Population:
• Treatment cohort: All fee for service Medicare enrollees undergoing sensor implant (6/2014–3/2016)
• Control cohort: Matched 1:1 using demographic traits, co-morbidities and timing of HF hospitalization

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Temporal Matching
Implant
0 12mo-12mo
Clinical
match
Clinical Matching
N=1176
1. Gender, Race, ICD or CRT, ESRD, Age ± 5 yrs
2. Co-morbidities: Arrhythmia, HTN, Diabetes,
Pulmonary and Renal disease
3. Closest match on propensity score
4. Exact match on HF history: # of HFH and non HFH
5. Closest match on hospitalization timing
N=1.5MHospitalizedfor HF
≥
N=1087*
* N = 89, No matches found
Statistical Methods
Outcome Methodology
All-cause mortality at 12 months Kaplan-Meyer analysis
HF hospitalizations at 12 months Anderson-Gill model for recurrent events
(censoring for death, VAD or transplant)
HFHospitalization: Pre-implant Period
Treatment Cohort Control Cohort p-value
Number of HFEvents 2532 2532 1.00NS
Avg. LOS—days/HFH 5.5± 4.9 4.9± 4.1 P<0.01
Total timeinhosp. —days/pt. 12.7± 12.7 11.4± 11.4 P=0.01
Cohort hosp. time—days 13857 12442 0.16

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784
616
0
200
400
600
800
HFH
Control Cohort Treatment Cohort
HFHospitalization: Post-implant Period
0.65
HFH/pt-year
0.88
HFH/pt-year
325
241
0
100
200
300
400
Death
Control Cohort Treatment Cohort
MortalityAfter Sensor Implant
0.22
MortalityRate
0.30
MortalityRate
ProbabilityofSurvival

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HF hospitalization Mortality
El implante de un sensor de TA se asoció a una
reducción de riesgo de mortalidad del 30% y del 24% en
los reingresos.
Es preciso un ensayo clínico que dé robustez a estos
hallazgos (GUIDE-HF trial)

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Josep Rodés-Cabau, MD, FACC
Quebec Heart & Lung Institute, Laval University
on behalf of V-Wave’s FIM/SAP Investigators
Interatrial Shuntingfor Treating
Heart Failure: EarlyandLate
Resultsof theFirst-in-Human
ExperienceWiththeV-Wave
Interatrial Shunt System
The V-Wave Shunt
Porcine pericardial leaflets
– Minimizes R to L shunting
and risk of paradoxical
embolization
Hourglass shape
– secure and atraumatic septal retention
– minimal ID 5.1 mm
ePTFE encapsulation
– Channels flow
– Impedes luminal obstruction due
to tissue ingrowth
Right Atrium Left Atrium
Self-expanding
Nitinol frame
Interatrial septum
Objective
• First-in-human prospective multicenter open-label experience to assess
the feasibility, safety and exploratory efficacy of interatrial shunting with
the V-Wave system for patients with heart failure (reduced and preserved
left ventricular ejection fraction)
Outcomes
• Primary
– Safety: device/procedure-related major adverse cardiovascular and neurological events
(MACNE), defined as death, stroke, device embolization, pericardial effusion requiring
intervention, re-intervention or surgery at 3- and 12-month follow-up
– Procedural success: successful device implantation with no periprocedural death
• Secondary
– Safety: all-cause MACNE, all serious adverse events (SAEs) and serious adverse device
effects (SADEs)
– Exploratory efficacy: changes in NYHA Class, quality of life, and 6MWT distance at 3- and
12-month follow-up

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• Procedures/Follow-Up
– Transfemoral venous
approach, general anesthesia,
TEE guidance
– Anticoagulation for at least 3
months
– Study follow-up (1, 3, 6, 12m
and yearly to 5 y)
Special Access Program
22 patients enrolled at 1 center in Canada
First-In-Man Multicenter Feasibility Study
16 patients enrolled in 5 centers in Israel and Spain
SAP
FIM
38 patients implanted (30 HFrEF, 8 HFpEF)
28 month median follow-up (Range 18-48 months)llow-up
Population

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Outcomes
/38
NE at 3M
Patients (n=38)
PROCEDURAL/IN-HOSPITAL
Successful device implantation 38 (100)
Shunt patency at procedural TEE 38 (100)
Device embolization/dislocation 0
Need for a 2nd device 0
Procedural time, min 72 ± 24
Hospitalization days (median, IQR) 1, 1-2
Device/procedure-related MACNE
Cardiac tamponade 1 (2.6%)
SAFETY OUTCOMES (full 12-month follow-up)
Cumulative device/procedure-related MACNEs
Death 0
Stroke 0
Cardiac tamponade 1 (2.6)
Device embolization 0
Device infection 0
Reintervention or surgery 0
Overall device/procedure-related MACNE 1 (2.6)
Cumulative all-cause MACNEs
Death 2 (5.2)
Stroke 0
Systemic embolism 0
Ventricular tachycardia 1 (2.6)
Myocardial infarction 0

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Functional,EchoandHemodynamicParameters
Variable
Baseline
(n=38)
3 Months
(n=36)
12 months
(n=36)
*p-value
Functional Status/Quality-of-Life
NYHA III-IV 38 (100) 8 (22) 14 (39)
<0.001
NYHA I-II 0 (0) 28 (78) 22 (61)
KCCQ/MLHFQ(improve≥5points) - 27 (74) 26 (73) <0.001
6-MWT (m) 290±112 340±94 324±105 0.012
Laboratory parameters
Ln NT-pro BNP (pg/mL) 7.5 ± 0.9 7.4 ± 1.0 7.5 ± 0.9 0.83
eGFR (ml·min-1·1.73 m-2) 54± 20 55 ± 23 53 ± 22 0.92
Echocardiographicvariables
LVEF (HFrEF, %) 26 ± 7 27 ± 9 28 ± 8 0.54
LVEF (HFpEF, %) 50 ± 9 52 ± 10 54 ± 9 0.74
MR Grade 3.9 ± 1.5 3.5 ± 1.2 3.5 ± 1.3 0.51
LAVI (ml/m2) 42 ± 13 42 ± 13 41 ± 15 0.84
TAPSE (mm) 16 ± 4 17 ± 4 16 ± 4 0.94
Qp/Qs 0.99 ± 0.11 1.17 ± 0.12 1.10 ± 0.13 0.005
Hemodynamics
PCWP (mmHg) 21 ± 5 20 ± 7 19 ± 7 0.49
RAP (mmHg) 8 ± 4 9 ± 5 9 ± 4 0.51
PAP, mean (mmHg) 30 ± 7 29 ± 8 30 ± 10 0.97
CI (L/min/m2) 2.2 ± 0.4 2.4 ± 0.4 2.3 ± 0.5 0.27
PVR (Wood Units) 2.8 ± 1.6 2.6 ± 1.1 2.8 ± 1.9 0.73
KCQC/MLHFQ (improve >5 points)

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Shunt ValveFunctionat 1-3and12Months(TEE)
A. Widely Patent Shunt B. Stenotic Shunt; narrowed/skewed C. Occluded Shunt
• Shunt patency at 1-3 months: 36/36 (100%)
• 12-month shunt occlusion: 5/36 (14%)
• 12-month shunt stenosis (TEE Color Doppler vena contracta in valve region narrowed/skewed): 13/36 (36%)
• No thrombus, no shunt migration, no erosion of adjacent structures
Patent Stenotic p
Vena Contracta 3.3±0.6 mm 1.5±1.5 mm 0.001
Qp:Qs 1.17±0.12 mm 1.05±0.12 mm 0.023
Pathological Examination(StenoticShunt)
2.5 year explant specimen from
transplanted patient
A. LA view. Orifice widely patent.
B. RA view. Pannus thickening with
stenosis of bioprosthetic
leaflets.
C. Axial Section (H&E).
Fibrocellular neoendocardium
(pannus) infiltration of leaflets.
D. SEM. Full endothelialization of
lumen (CD31+)

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HemodynamicChangesGroupedbyShunt Patencyat 1-Year Follow-Up
Patent ≥ Stenotic/Occluded ≥
At baseline,
patients with
patent shunts were:
• Older
• AF
• eGFR
• 6MWT
• PCWP, CO
Long-termClinical OutcomesGroupedbyShunt Patency

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ComparisonwithCMEMsChampionStudy
Studies had similar:
• eligibility criteria
• baseline characteristics
including
hemodynamics
• use of medical and
device therapies
including dosing

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• El shunt interauricular con el dispositivo V-Wave es
seguro y parece relacionarse con mejoría funcional y
reducción de eventos cardiovasculares
•Existe una alta tasa de estenosis/oclusión del
dispositivo al año (pannus) y ésta se asoció a peor
perfil hemodinámico y más eventos