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 » )