Transcript Diapositive 1 - Gastaldi Congressi

LUNCHEON PANEL II:
PROGRESSI IN CRT
(ADVANCES IN CRT)
Come predire eventi acuti HF
nei pz CRT: risultati e prospettive
How to Predict Acute HF Events
in CRT pts: Results & Perspectives
Maurizio LUNATI, MD
Cardiology Dptm – Electrophysiology
Ospedale Ca’ Granda Niguarda, MILANO, Italy
Devices for HF …
“Preventive CRT” & CRT devices
WHY to “monitor HF” in CRT pts ?
Symptoms = Tip of Congestion Iceberg in HF
S
Y
M
P
T
O
M
S
Systemic congestion
(JVD, edema)
 Hydrostatic pressure
 Oncotic pressure
 Permeability
Lymphatic drainage
capacity
Alveolar-capillary
membrane integrity
Abnormal lung function
Respiratory muscle dysfunction
Other factors
 RV + RA pressure
Increase PA pressure
Increased PCWP (congestion )
Dyspnea
Alveolar edema
Redistribution in
pulmonary vascular bed
+ Interstitial edema
 LA and LV diastolic pressure
LVDP + Impaired volume regulation
Abnormal LV function (Syst. &/or Dias.)
Mitral
Regurgitation
WHY predict acute HF events is important …
Functional
Capacity
With each event, myocardial injury (as shown by Tn release)
might occur, contributing to the progressive ventricular
dysfunction and dilatation
Acute event
Jain P, Massie BM & al.
Am Heart J 2003; 145: S3-S17
Time
To-date tools to “Monitor HF”
Gavazzi A. Lo scompenso cardiaco (p. 139). Editors “Scripta Manent” (2002)
•
•
•
•
•
Signs & symptoms
Body weight
Natriuretic peptides (BNP, NT-proBNP)
Hemodynamic sensors
Data from implantable devices
(ICD, CRT, CCM, …)
Are clinical & instrumental variables
USEFUL to accurately track HF ?
Several NON-INVASIVE variables have been commonly
used to assess the clinical & functional status in HF pts,
but generally they are NOT a lot useful to predict the
clinical evolution, because:
 influenced by psychological or subjective factors
(NYHA class, dyspnea, QoL)
 useful to describe the status @ FU time only
(echocardio, 6’ WT, ergometric test)
 predict worsening with a very short predictive delay
(body weight, edema)
The way towards an acute HF event …
100%
Dyspnea under effort
80%
Dyspnea at rest
Ortopnea
60%
40%
20%
35
30
25
20
15
10
5
0
Days
0%
(before HFH)
Schiff & al. Am J Med 2003; 114: 625
% cumulative of pts who experienced
Edema
Weight increase
Data today monitored
(implemented in therapeutic
implantable devices)
•
•
•
•
•
Heart Rate Variability
Physical activity
Fluid accumulation (impedance measurement)
Minute ventilation
…?
HRV: SDAAM, nocturnal HR & physical activity
[ 3 months before HFH ]
SDAAM
standard deviation of 5 min
median atrial-atrial intervals
sensed by the device
n = 34 pts
Adamson P. & al. Circulation 2004; 110: 2389-94
Fluid accumulation monitoring with OptiVol
“Dry” lungs 
High impedance
Better
“Wet” lungs 
Low impedance
Worse
OptiVol: MAIN findings
Yu CM & al. Circulation 2005; 112: 841-8




33 pts, NYHA class III / IV, FU: 20 ± 8.4 M
Predictive delay: 15.3 ± 10.6 days
Sensitivity = 76.9 %
False Positives = 1.5 unnecessary visits / year / pt
Vollmann D & al. Eur Heart J 2007




373 CRT-D pts, median FU 4.2 M, Alert = ON in all pts
Reported all clinical data (HF) vs telemetry of CRT-Ds
Sensitivity & PPV: 60% (33/53, adjusted by multiple events/pt)
20 alerts not given upon “true HF events”
Ypenburg C & al. Am J Cardiol 2007
 115 CRT-D pts; FU time 9±5 M; Alert = ON (empiric threshold 60 omega)
 HF clinical data retrieved in case of ALERT heard by pt
 ROC curve  optimal alert threshold = 120 omega
- sensitivity 60%
- specificity 73%
Usefulness of the alert in clinical practice
Monitoring Intrathoracic Impedance with an
Implantable Defibrillator Reduces Hospitalizations
in Patients with Heart Failure
Catanzariti D, Lunati M, Landolina M, Zanotto G, Lonardi G, Iacopino S, Oliva F, Perego GB, Varbaro A,
Denaro A, Valsecchi S, Vergara G; Italian Clinical Service Optivol-CRT Group
Pacing Clin Electrophysiol. 2009 Mar;32(3):363-70
Events of reduced Impedance and associated
clinical events.
67 % of True Detection of
Relevant Clinical Events
Time to cardiac death, heart transplantation
and heart failure hospitalization
unexplained or
untreated
Alerts: 0.25 per
patient-year
(N=430)
The ICD reliably detected Clinical
Events and yielded low rates of
unexplained and undetected
events.
(N=102)
The alert reduces the number of
HF hospitalizations by allowing
timely detection and therapeutic
intervention
Risk stratification by device diagnostic trends
Implantable CRT device diagnostics identify patients with
increased risk for heart failure hospitalization
Perego GB, Landolina M, Vergara G, Lunati M, Zanotto G, Pappone A, Lonardi G, Speca G,
Iacopino S, Varbaro A, Sarkar S, Hettrick DA, Denaro A; Optivol-CRT Clinical Service
Observational Group.
J Interv Card Electrophysiol. 2008 Dec;23(3):235-42
558 HF patients
Decreased intra-thoracic impedance is associated to a 36% increased risk
for HF hospitalization in a population of HF patients treated with CRT.
Other device parameters including patient activity, VT episodes, NHR
and HRV are prognostic predictors of Acute HF events and can be
associated to intra-thoracic impedance to better evaluate the risk of Acute
HF events.
Efficacy of the remote follow-ups
"Remote Monitoring of Patients with Biventricular Defibrillators
Through the CareLink System Improves Clinical Management of
Arrhythmias and Heart Failure Episodes”,
M. Santini, R.P. Ricci, M. Lunati, M. Landolina, G.B. Perego, M. Marzegalli, M. Schirru, C.
Belvito, R. Brambilla, G. Guenzati, S. Gilardi, S. Valsecchi
J Interv Card Electrophysiol 2009 Jan;24(1):53-61
The remote
monitoring systems
(CareLink network)
may increase the
efficacy of the
OptiVol algorithm
by allowing the
early detection and
remote review of
clinical events
An expert system with the aim to:
Continuously monitor the pt’s functional status with
multi-sensor capability
Predict acute HF events to prevent the (probable)
related hospitalizations
Daily & weekly analysis of variables
PhD = software (Rules & Meta-rules) to interpretate
the trend of variables (daily & weekly basis)
MV under EFFORT
phases
PhD alert
( rule of MV rest  )
MV in RESTING
phases
Physical Activity (Workload)
Stable Workload,
MV rest progressive 
At the end of this FU, the pt was hospitalized for HF
System Tuning & “reaction” times
MV exer
AUTOMATIC
“TUNING” of
PhD function
(about 1M)
SUB-CLINICAL
phase of
ACUTE episode
CLINICAL
phase
MV rest
Workload
Page E, Cazeau S & al. Europace 2007; 9: 687-93
Clinical case #1 (impl ►M3):
step-by-step worsening
X:
O:
+:
rule W
rule MVA
rule MVR
--------: ALERT on meta-rule MVR
--------: ALERT on meta-rule W
MV exer
3
W
8
5
20 days
7
4
2
1
6
MV rest
Last 90 days
9
9
9
10
1.
2.
3.
4.
5.
6.
7.
8.
9.
Post-implant: pt OK
Pt starts moderate W
MV-exer increases (physiolog.)
Pt increases level of W
MV-exer increases
MV-rest increases (compensation)
Pt worsens, reduces W
MV-exer decreases, not a lot …
MV-rest not back to prev. values;
slow drifting increase …
10. HFH …
Next step: prospective evaluation
• Trial under submission (2H-2009 / 2010)
• Size: 430 CRT-D pts in 50 Centers among Europe, US & Canada
• 1-ary endpoint: % sensitivity of PhD (MV & workload)
• Monthly Phone Call: to appropriately track ALL clinical events
INCLUSION /
IMPLANT
FU M4
FU M1
- fu ICD
- BNP
- QoL
Every 3M …
FU M7
- fu ICD
- BNP
- QoL
- fu ICD
- BNP
- QoL
- fu ICD
- BNP
- QoL
PhD = ON
(ALL pts)
M2
M3
M5
M6
M8
M9
Tools for HEMODYNAMIC monitoring
RVDP
RVSP
Wadas
TM. Critical Care Nurse 2005; Vol. 25 n. 5: Cover Article
HR
CHRONICLE (Medtronic) investig. device; (IHM = implantable hemodynamic monitor)
Adamson P & al. Clin Cardiol. 2007; 30: 567-75
Mechanical vibrations
& sonR
The mechanical vibrations generated by
the system “myocardium + blood”
might be detected by a sensor (sonR),
a micro- accelerometer realized in the
tip of a standard permanent pacing lead
sonR & FU:
trend of contractility
Pt included in the CLEAR trial
M, 78 y old; idiopathic dilated CMP, NYHA III
implant of CRT-P (NewLiving CHF) in Nov. 2005
sonR values: 24h post-implant (green), vs
last 24h before M1 FU visit (red)
M1 FU visit:
Peripheral edema
Reduction 0,8►0,4 sonR ampl.
Hospitalization (8 days)
0.4g @ M1
0.8g @ Implant
sonR (g)
sonR & FU:
0,7g
trend of contractility
Last month
1
0,5g
0,65g
Last
week
2
0,4g
Last
24h
0,63g
3
HFH (8 d)
Diuretics
Peripheral edema
sonR (0,7g►0,4g)
Discharge
sonR (0,4g►0,65g)
Follow-up M3
Stable situation
sonR (0,65g)
Time
Trend amplitude sonR signal
Post-implant sonR value restored …
… and maintained at 3M FU visit
0.63 g M3
0.65 g
M1+1wk
The key for future: multi-sensor systems
Physical activity
(G): workload
sonR sensor:
contractility
( LVdP/dt)
Minute Ventilation (MV):
respiratory dynamics
HRV:
ANS activity
(pNN-50; SDAAM; etc.)
The evolution of PhD function
( « Advanced PhD » )
MV exercise
&
Info on functional
status
MV rest
Workload (G)
Tomorrow:
(contractility  endocardial acceleration)
Tomorrow:
automatic ALERTS