Insuffisance cardiaque avancée

prévalence, mortalité, coût,

facteurs de réticence au LVAD

Jean-Noël Trochu
Institut du Thorax
CHU de Nantes
France
Agenda

l Advanced heart failure patients

l Definition
l Epidemiology
l Cost
l Prognosis, indication, reluctances
l Organization of care
l Early / late referral
l Conclusion
The cascade of advanced heart failure

Ageing of the population ACEi, ARNi, BB, ARB, Spiro, glyfozines,

Improv. tt HBP, AMI vericiguat, ivabradine, CRT
¯ mortality
­ HF prevalence

­ pts with severe symptoms

Poor QOL, high mortality related to WHF
ADVANCED CHRONIC HEART FAILURE

­ indication / use of ICDs

¯¯ suden death
 Clinical course of HF Unable to carry on
any physical activity
Asymptomatic Symptomatic severe end stage
without symptoms
of HF, or symptoms
of HF at rest
NYHA III IV

ACC/AHA stage C D

Patients have current or prior symptoms of HF

Dyspnea, fatigue due to HF, on treatment for
previous HF

Advanced structural heart disease who require

specialized interventions
Severe impairment in functional capacity
Attempts to optimize medical tmt, frequent HF hospitalizations
awaiting cardiac transplant, IV inotropes or VAD

Death
 l ∼ 50% of patients with LVSD have no or only mild HF symptoms
l NYHA functional classification gauges the severity of symptoms in pts with structural heart disease, stages C and D
l subjective assessment by a clinician
l can change frequently over short periods of time
l reproducibility and validity may be problematic
l Independent predictor of mortality
l Used in clinical practice and research

Yancy. JACC 2013;62:e147–239/ McDonagh TA Lancet 1997;350:829–833 / Davies M Lancet 2001;358:439–444

 8 km/h

Goldman L. Circulation 64, No. 6, 1981.

Goldman L. Circulation 64, No. 6, 1981.
 Correlation of the New York Heart Association classification
and the cardiopulmonary exercise test: A systematic review.

23.8

17.6

13.3

12.5

Forman DE. J Am Coll Cardiol 2012;60:2653–61 Lim FY Int J Cardiol. 2018;263:88-93.

 Clinical course of HF

Confirm

Fluid removal, continuous inotropic infusions

Palliative care?

Desai AS, Stevenson LW. Circulation. 2012;126:501-506

Which treatments?

Heart transplantation Assistance device Total artificial heart

LVAD
 ESC definition of AHF

l 1. Symptoms and signs of HF

a- Dyspnea or fatigue at rest with minimal exertion (NYHA III or IV)
b- Episodes of fluid retention and/or reduced cardiac output at rest (peripheral hypoperfusion)

l 2. Objective evidence of severe cardiac dysfunction

a- low EF < 30%
b- severe abnormality of cardiac function on Doppler-echo with a pseudonormal or restrictive
mitral inflow pattern
c- high left ventricular filling pressure (mPCWP > 16 mm Hg and/or mRAP > 12 mm Hg)
d- High BNP or NT-ProBNP plasma levels, in the absence of non-cardiac causes

Metra et al. European J Heart Fail. 2007;9:684

 ESC definition of AHF

l 3. Severe impairment of functional capacity:

a- Inability to exercise,
b- 6-MWT distance < 300 m or less in females and/or patients aged ≥ 75 years
c- peak VO2 < 12 to 14 ml/kg/min

l 4. History of ≥ 1 HF hospitalization during past 6 months

l 5. Presence of all the previous features despite “attempts

to optimise” therapy including diuretics, ACE inhibitors /AMR and beta-
blockers, unless these are poorly tolerated or contraindicated, and CRT, when indicated

Metra et al. European J Heart Fail. 2007;9:684

Crespo-Leiro MG. European Journal of Heart Failure (2018)
l Advanced HF, end-stage HF, refractory HF
l In the 2009 ACCF/AHA HF guideline,
stage D:
l “pts with truly refractory HF who might be eligible
for specialized, advanced treatment strategies,
such as MCS, procedures to facilitate fluid
removal, continuous inotropic infusions, or
cardiac transplantation or other innovative or
experimental surgical procedures, or for end-of-
life care, such as hospice”
Yancy CW. JACC Vol. 62, No. 16, 2013
Hunt SA, JACC 2009;53:e1–90
l Acute decompensated HF is not
always AHF
l Pts with NYHA class IV symptoms at their
index HF presentation yet are not considered
to have advanced disease
l => response to treatment of etiologic factors
and optimization of tt and to NYHA classes
I or II
ACC/AHA Definition
(Clinical events and findings useful for identiying pts with advanced HF)

Hunt. J Am Coll Cardiol 2009;53:e1–e90

Yancy. Circulation 2013;128:1810–1852
Fang JC. J Cardiac Fail 2015;21:519e534
 Definition HF Society of America
• Need for intravenous inotropic therapy for
symptomatic relief or to maintain end-organ function
• Peak VO2 <14 mL/kg/min or <50% of predicted
• 6MWT distance <300m
• ≥2 HF admissions in the last 12 months
• >2 unscheduled visits (e.g. ED or clinic) in the last 12
months
• Worsening right HF and secondary pulmonary
hypertension
• Diuretic refractoriness associated with worsening
renal function
• Circulatory–renal limitation to RAAS inhibition or beta-
blocker therapy
Fang JC. J Card Fail. 2015 Jun;21(6):519-34.
• Progressive/persistent NYHA class III–IV
symptoms
• Increased 1-year mortality (e.g. 20–25%)
predicted by HF survival models (e.g. SHFS, HFSS,
etc.)
• Progressive renal or hepatic end-organ
dysfunction
• Persistent hyponatraemia (serum Na <134 mEq/L)
• Recurrent refractory ventricular tachyarrhythmias;
frequent ICD shocks
• Cardiac cachexia
• Inability to perform ADL
 INTERMACS classification
Clinical assessment of severity of AHF

Lietz. Curr Opin Cardiol 24:246–251

Intermacs classification
Epidemiology
 Nombre de patients en insuffisance cardiaque
avancée aux USA en 2010
~240 millions Population
≥ age 20 ans

~50 % IC FEVG préservée IC =2,6 % population* ou 80-85% Stade A-

3,12 M 6,24 million Total B

15-20% Stade C
(3-4% stade C
~50 % altération avancé)
contraction 3,12 million
0.5-5 % Stade D

Stade C avancé / NYHA class IIIB Stade D / NYHA functional class IV

93.600-124.800 15.600-156.000

Stades C avancé et D ≥ age 20 ans 75% contre-indications

109.200 – 280.800 70 000 Tx/LVAD
Adapted from Starling, Gorodeski in press
Cost
Circ Heart Fail. 2014;7:470-478
Tadmouri A. ESC Heart Failure 2018; 5: 75–86
Prognosis, indication, reluctances
 Survival in advanced heart failure

UNOS Status 1

UNOS Status 2

• Heterogeneous group
- 30% to 40% of ambulatory HTx candidates require upgrade to
high urgency status or emergency MCS implantation
- Risk stratification
• Very poor QOL
Lietz JACC 2007;50:1282
2009 focused update recommendations
Patients with refractory end stage HF (D)

• Thorough evaluation
• remediable etiologies / alternative
explanations for advanced symptoms
• Non-adherence to tt, Na restriction,
daily weight monitoring
• all evidence-based therapies likely to
improve clinical status have been
considered
Hunt et al. 2005
Recommendations for Cardiopulmonary
Stress Testing to Guide Transplant Listing

l Class I:
l 1. A maximal cardiopulmonary exercise (CPX) test is defined as one
with a respiratory exchange ratio (RER) 1.05 and achievement of an
anaerobic threshold on optimal pharmacologic therapy (Level of
Evidence: B).
l 2. In patients intolerant of a beta-blocker, a cutoff for peak VO2 of
14 ml/kg/min should be used to guide listing (Level of Evidence: B).
l 3. In the presence of a beta-blocker, a cutoff for peak VO2 of 12
ml/kg/min should be used to guide listing (Level of Evidence: B).
l Class IIa:
l 1. In young patients (50 years) and women, it is reasonable to
consider using alternate standards in conjunction with peak VO2 to
guide listing, including percent of predicted (50%) peak VO2
(Level of Evidence: B).

Listing criteria for HTx, ISHLT guidelines 2006,

Mehra J Heart Lung Transplant 2006;25:1024
 Cardiopulmonary Exercise Testing and
Prognosis in Chronic Heart Failure.
A Prognosticating Algorithm for the Individual
Patient
VO2 max (anaerobic threshold achieved)

VO2 max VO2 max VO2 max

< 10 ml/kg/min 10-18 ml/kg/min > 18 ml/kg/min

VE/VCO2 > 35 VE/VCO2 < 35

High Medium Low

risk risk risk

Corra U. CHEST 2004;126:942–950.

 In the course of standard evaluation, clinicians should routinely assess the
patient’s potential for adverse outcome, because accurate risk stratification
may help guide therapeutic decision making, including a more rapid transition
to advanced HF therapies

Yancy CW. JACC Vol. 62, No. 16, 2013

Mehra MR. JHLT 2016
65 years old man, NYHA IIIB
1 0,6931
80 1,728
20 -0,928
70 -1,785
1 0,6083
12 -0,6552
132 -6,204 ∑= 6.543

Criteria for HTx listing or DT-LVAD

VO2 peak VO2 hi risk med risk lo risk
Tolerate Bbl:
no: ≤ 14 ml/min/kg, yes: ≤ 12 ml/kg/min ml/kg/min ≤ 10 10.1-14 > 14
1-yr surv. 65% 77% 87%

HFSS HFSS hi risk med risk lo risk

score ≤ 7.19 7.20-8.09 ≥ 8.10

1-yr surv. 60% 72% 89%

Courtesy of L. Lund
 MAGGIC meta analysis : Reduced and preserved HF, 30 cohort studies (6 clinical trials) 40% died median FU 2.5 years
www.heartfailurerisk.org

Pocock SJ. European Heart Journal doi:10.1093/eurheartj/ehs337

www.heartfailurerisk.org
 Clinical assessment
No
t of severity of HF
br
oa
dly
ac Intermacs classification
ce
pte
Gde
ne
ra
lly
ac
ce
pt
ed

Lietz K, Miller WM. Curr Opin Cardiol 2009;24:246

Kirklin JK. J HeartLungTransplant2015;34:1495–1504
Mehra MR . N Engl J Med 2017;376:440-50.
Composite primary end point: survival at 2 years free of disabling stroke or survival free of reoperation to replace or remove a malfunctioning device

Mehra MR. N Engl J Med 2018;378:1386-95. Mehra MR. N Engl J Med 2019;380:1618-27.
Mehra MR. N Engl J Med 2019;380:1618-27.
Kirklin JK. J HeartLungTransplant 2016;35:407–412
Kirklin JK. J HeartLungTransplant 2015;34:1495–1504
 mortality and morbidity, 33 073 HTx candidates registered on the UNOS
waiting list between 1999 and 2011

Wever-Pinzon O. Circulation. 2013;127:452-462

 CF LVAD bridging is no longer associated
with increased mortality after HTx

2005 – 06/2012

Lund L. JHLT 2013;951

 1 year mortality btw HTX and LVAD BTT

Thoechari CA.Ann Cardiothorac Surg 2018;7(1):3-11

 1 year mortality btw HTX and LVAD DT

Thoechari CA.Ann Cardiothorac Surg 2018;7(1):3-11

Kirklin JK. J HeartLungTransplant2015;34:1495–1504
 Clinical assessment
No
t of severity of HF
br
oa
dly
ac Intermacs classification
ce
pte
d

Lietz K, Miller WM. Curr Opin Cardiol 2009;24:246

Estep JD. J Am Coll Cardiol 2015;66:1747–61
Estep JD. J Am Coll Cardiol 2015;66:1747–61
Estep JD. J Am Coll Cardiol 2015;66:1747–61
Thompson JS. J Am Coll Cardiol HF 2015;3:965–76
What might my life look
with each option?
 Underutilization of heart transplantation and left
ventricular assist device - main results from the
ScrEEning for advanced Heart Failure treatment
(SEE-HF) study
ClinicalTrials.gov: NCT01626404
Steering Committee:
Lars H. Lund, Stockholm; Finn Gustafsson, Copenhagen;
Jean-Noël Trochu, Nantes; Laura Damme, Thoratec
Investigators:
J Schmitto, Hannover; D Schibilsky, Tuebingen; K Caliskan, Rotterdam; B Meyns, Leuven; S
Shaw, South Manchester
Data management and Biostatistics: J Heatley, Thoratec
Research funding: Thoratec, Inc.
 Aims

Primary objective:

To determine the proportion 8 centers

of out-patients with 7 countries
6/8 with transplant program
• NYHA III-IV heart failure 5/8 DT approval
• EF ≤ 40% CRT/ICD program size ~100-500 devices per
• and CRT and/or ICD in year
place

Who are candidates for heart

transplantation or LVAD

Hypothesis:

The prevalence is 10% ± 3%

Results
Inclusion criteria:
• CRT and/or ICD in place
• NYHA III-IV heart failure
• EF ≤ 40% ever
• OMM

Exclusion criteria:
• Age < 18 or > 80 y
• CRT < 3 months
• Only ICD
but CRT indicated
• CABG / PCI < 3 months
• Previous HTx or LVAD
• Hospitalized, dementia,
dialysis, O2-dependent,
life expectancy
due (other than HF)
< 2 years

Variable Screened Enrolled

n = 1722 n = 99
Age, mean 56 years 61 years
Gender, female % 26 % 19 %

Enrolled / eligible range 2–15%

 Results

Primary endpoint:
27% of out-patients with CRT and/or ICD, NYHA III-IV heart failure, and EF ≤ 40% are
eligible for HTx or LVAD
* Indications and contraindications not mutually exclusive
Results
When to refer and organization of care
 Organization fo care and referral
ESC

Crespo-Leiro MG. EJHF (2018)

Hub and Spoke organization

Crespo-Leiro MG. European Journal of Heart Failure (2018)

Late referrral of pts for consideration
of advanced HF therapies
l increases the risks of:
l right HF
l renal
l liver dysfunction
l pulmonary hypertension
l cardiac cachexia
l factors associated with:
l poorer outcomes after advanced HF therapies,
l patients being considered too unwell to undergo these treatment
 I NEED HELP
Timing to refer
l When pts progress from stable
HF to advanced HF
l “I Need Help” acronym
l encompasses many of the core
components for defining
advanced HF (US/ESC)
l timely referral / discussions with
advanced HF units
l if pt has ANY of the risk factors
l Extent of renal/liver dysfunction,
degree of NP/diuretics not well
defined
Adapted from Baumwol J. www.jhltonline.org
Crespo-Leiro MG. European Journal of Heart Failure (2018)
 l 1) Is transplantation or LVAD placement indicated?
l 2) Are there any contraindications?
l 3) If the patient is deemed « a transplantation candidate »,
l when should an implantable LVAD be considered as a bridge to
transplantation?
l If the patient is deemed « not a transplantation candidate »,
l can he or she still benefit from and qualify for a long-term LVAD?

Guglin, M. et al. J Am Coll Cardiol. 2020;75(12):1471–87.

Guglin, M. et al. J Am Coll Cardiol. 2020;75(12):1471–87.
Conclusion
l Epidemiology of advanced heart failure in Europe is still not well known, patient
identification, care and follow up are not optimised

l Patients are always referred to late to specialized heart failure clinics, with biventricular
dysfunction making LVAD and heart transplantation very difficult

l In order to better identify the patients simple clinical parameters and risk scores should
be used: Heart Failure Survival Score/Seattle Heart Failure Model) but are underused
although they are clinically pertinent / I NEED HELP

l Patient have to be closely followed by highly specialised heart failure clinics and general
cardiologists, RV function and pulmonary pressure must be closely monitored

l Heart transplantation, LVAD (and total artificial) heart are very efficient treatments but
misjudged