Post on 13-Apr-2017
Come predire eventi acuti HFCome predire eventi acuti HFnei pz CRT: risultati e prospettivenei pz CRT: risultati e prospettive
How to Predict Acute HF EventsHow to Predict Acute HF Eventsin CRT pts: Results & Perspectivesin CRT pts: Results & Perspectives
Maurizio LUNATI, MDMaurizio LUNATI, MD
Cardiology Dptm – ElectrophysiologyCardiology Dptm – ElectrophysiologyOspedale Ca’ Granda Niguarda, Ospedale Ca’ Granda Niguarda, MILANOMILANO, Italy, Italy
LUNCHEON PANEL II: LUNCHEON PANEL II:
PROGRESSI IN CRTPROGRESSI IN CRT(ADVANCES IN CRT)(ADVANCES IN CRT)
Devices for HF …Devices for HF …
““Preventive CRT” & CRT devicesPreventive CRT” & CRT devices
Increase PA pressure
Systemic congestion
(JVD, edema)
RV + RA pressure
SYMPTOMS
WHY to “monitor HF” in CRT pts ?
Symptoms = Tip of Congestion Iceberg in HF
Abnormal LV function (Syst. &/or Dias.)
LA and LV diastolic pressure
LVDP + Impaired volume regulation
Dyspnea
Increased PCWP (congestion ) Redistribution in pulmonary vascular
bed+ Interstitial edema
Alveolar edema
Hydrostatic pressure Oncotic pressure Permeability Lymphatic drainage capacityAlveolar-capillary membrane integrity
MitralRegurgitatio
n
Abnormal lung functionRespiratory muscle dysfunctionOther factors
WHY predict acute HF events is important …WHY predict acute HF events is important …
Acute Acute eventevent
TimeTime
Func
tiona
l Fu
nctio
nal
Cap
acity
Cap
acity
With each event, myocardial injury (as shown by Tn With each event, myocardial injury (as shown by Tn release) might occur, contributing to the progressive release) might occur, contributing to the progressive
ventricular dysfunction and dilatationventricular dysfunction and dilatation
Jain P, Massie BM & al.Am Heart J 2003; 145: S3-S17
To-date tools to “Monitor To-date tools to “Monitor HF”HF”
• Signs & symptomsSigns & symptoms• Body weightBody weight• Natriuretic peptides (BNP, NT-Natriuretic peptides (BNP, NT-
proBNP)proBNP)• Hemodynamic sensorsHemodynamic sensors• Data from implantable devicesData from implantable devices
(ICD, CRT, CCM, …)(ICD, CRT, CCM, …)
Gavazzi A. Lo scompenso cardiaco (p. 139). Editors “Scripta Manent” (2002)
Are clinical & instrumental variablesAre clinical & instrumental variables USEFUL to accurately track HFUSEFUL to accurately track HF? ?
Several NON-INVASIVE variables have been Several NON-INVASIVE variables have been commonly used to assess the clinical & functional commonly used to assess the clinical & functional status in HF pts, but generally they are status in HF pts, but generally they are NOT a lot NOT a lot usefuluseful to predict the clinical evolution, because:to predict the clinical evolution, because:
influenced by influenced by psychological or subjective psychological or subjective factorsfactors (NYHA class, dyspnea, QoL)(NYHA class, dyspnea, QoL)
useful to describe the useful to describe the status @ FU time onlystatus @ FU time only(echocardio, 6’ WT, ergometric test)(echocardio, 6’ WT, ergometric test)
predict worsening with a predict worsening with a very short predictive very short predictive delaydelay (body weight, edema)(body weight, edema)
The way towards an acute HF event The way towards an acute HF event ……
Schiff & al. Am J Med 2003; 114: 625Schiff & al. Am J Med 2003; 114: 625
DaysDays(before HFH)(before HFH)
100%
80%
60%
40%
20%
0%
% cum
ulative of pts who experienced%
cumulative of pts who experienced
35 30 20 10 051525
EdemaEdemaWeight increaseWeight increaseDyspnea under effortDyspnea under effortDyspnea at restDyspnea at restOrtopneaOrtopnea
Data today monitoredData today monitored(implemented in therapeutic (implemented in therapeutic
implantable devices)implantable devices)
• Heart Rate Variability Heart Rate Variability • Physical activityPhysical activity• Fluid accumulation Fluid accumulation (impedance (impedance
measurement)measurement)
• Minute ventilationMinute ventilation• … … ??
HRV: SDAAM, nocturnal HR & physical HRV: SDAAM, nocturnal HR & physical activityactivity
[ 3 months before HFH ][ 3 months before HFH ]
n = 34 n = 34 ptspts
Adamson P. & al. Circulation 2004; 110: 2389-94Adamson P. & al. Circulation 2004; 110: 2389-94
SDAAMstandard deviation of 5 minmedian atrial-atrial intervals
sensed by the device
““Dry” lungs Dry” lungs High impedanceHigh impedance
BetterBetter
““Wet” lungs Wet” lungs Low impedanceLow impedance
WorseWorse
Fluid accumulation monitoring with Fluid accumulation monitoring with OptiVolOptiVol
OptiVol: MAIN findingsOptiVol: MAIN findingsYu CM & al. Circulation 2005;Yu CM & al. Circulation 2005; 112: 841-8112: 841-8
33 pts33 pts, NYHA class III / IV, FU: 20 , NYHA class III / IV, FU: 20 ±± 8.4 M 8.4 M Predictive delay:Predictive delay: 15.3 15.3 ± ± 10.6 days10.6 days Sensitivity = Sensitivity = 76.9 %76.9 % False Positives = 1.5 unnecessary visits / year / ptFalse Positives = 1.5 unnecessary visits / year / pt
Vollmann D & al. Eur Heart J 2007Vollmann 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 2007Ypenburg 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%
Monitoring Intrathoracic Impedance with anImplantable Defibrillator Reduces Hospitalizationsin Patients with Heart FailureCatanzariti 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
The alert reduces the number of HF hospitalizations by allowing timely detection and therapeutic intervention
Usefulness of the alert in clinical practiceUsefulness of the alert in clinical practice
The ICD reliably detected Clinical Events and yielded low rates of unexplained and undetected events.
Time to cardiac death, heart transplantation and heart failure hospitalization
67 % of True Detection of 67 % of True Detection of Relevant Clinical EventsRelevant Clinical Events
unexplained or unexplained or untreated untreated Alerts: 0.25 per Alerts: 0.25 per patient-year patient-year
Events of reduced Impedance and associated clinical events.
(N=430) (N=102)
Implantable CRT device diagnostics identify patients with increased risk for heart failure hospitalizationPerego 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
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.
Risk stratification by device diagnostic trendsRisk stratification by device diagnostic trends
558 HF patients
"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
Efficacy of the remote follow-ups Efficacy of the remote follow-ups
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
At the end of this FU, the pt was hospitalized for HF
Stable Workload, MV rest progressive
PhD alert( rule of MV rest )
MV under EFFORT phases
MV in RESTING phasesPhysical Activity
(Workload)
PhD = software (Rules & Meta-rules) to interpretate the trend of variables (daily & weekly basis)
Daily & weekly analysis of variablesDaily & weekly analysis of variables
SUB-CLINICALphase of
ACUTE episode
CLINICALphase
AUTOMATICAUTOMATIC““TUNING” ofTUNING” ofPhD functionPhD function
(about 1M)(about 1M)
Page E, Cazeau S & al. Europace 2007; 9: 687-93
MV exer
MV rest
Workload
System Tuning & “reaction” timesSystem Tuning & “reaction” times
Clinical case #1 (impl ►M3): Clinical case #1 (impl ►M3): step-by-step worseningstep-by-step worsening
MV exer
W
MV restLast 90 days
X: rule WOO: rule MVA+: rule MVR
--------: ALERT on meta-rule MVR--------: ALERT on meta-rule W
1. Post-implant: pt OK2. Pt starts moderate W3. MV-exer increases (physiolog.)4. Pt increases level of W5. MV-exer increases6. MV-rest increases (compensation)7. Pt worsens, reduces W8. MV-exer decreases, not a lot …9. MV-rest not back to prev. values;
slow drifting increase …10. HFH …
20 days
12
34
5
67
8 9
99
10
• 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 M1 FU M4 FU M7 Every 3M …
- fu ICD- BNP- QoL
- fu ICD- BNP- QoL
- fu ICD- BNP- QoL
- fu ICD- BNP- QoL
PhD = ON(ALL pts)
M2 M3 M5 M6 M8 M9
Next step: prospective evaluationNext step: prospective evaluation
Tools for HEMODYNAMIC monitoringTools for HEMODYNAMIC monitoring
Wadas TM. Critical Care Nurse 2005; Vol. 25 n. 5: Cover ArticleCHRONICLE (Medtronic) investig. device; (IHM = implantable hemodynamic monitor)
RVDPRVDP
RVSPRVSP
HRHR
Adamson P & al. Clin Cardiol. 2007; 30: 567-75
Mechanical vibrations Mechanical vibrations & sonR& 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
Pt included in the CLEAR trialM, 78 y old; idiopathic dilated CMP, NYHA IIIimplant of CRT-P (NewLiving CHF) in Nov. 2005
M1 FU visit: Peripheral edema Reduction 0,8►0,4 sonR ampl. Hospitalization (8 days)
0.4g @ M1
0.8g @ Implant
sonR values: 24h post-implant (green), vs last 24h before M1 FU visit (red)
sonR & FU:sonR & FU: trend of contractilitytrend of contractility
Trend amplitude sonR signal Post-implant sonR value restored … … and maintained at 3M FU visit
Time
sonR
(g)
Last month
Last week
Last24h
1
0,7g
0,5g
0,4g
0.65 g M1+1wk
0.63 g M3
3
Peripheral edemasonR (0,7g►0,4g)
HFH (8 d)Diuretics
DischargesonR (0,4g►0,65g)
Follow-up M3Stable situationsonR (0,65g)
2
0,65g 0,63g
sonR & FU:sonR & FU: trend of contractilitytrend of contractility
Physical activity (G): workload
Minute Ventilation (MV):
respiratory dynamics
sonR sensor:contractility ( LVdP/dt)
The key for future: multi-sensor systemsThe key for future: multi-sensor systems
HRV:ANS activity (pNN-50; SDAAM; etc.)
MV exerciseMV exercise
MV restMV rest
Workload (G)Workload (G)
Info on functionalInfo on functionalstatusstatus
Tomorrow:Tomorrow:automatic ALERTSautomatic ALERTS
Tomorrow:Tomorrow:(contractility (contractility endocardial acceleration) endocardial acceleration)
&The evolution of PhD functionThe evolution of PhD function( « Advanced PhD » )( « Advanced PhD » )