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Innovazione nel settore dei dispositivi medici GF Gensini Roma, 20 dicembre 2016

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Page 1: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Innovazione nel settore dei dispositivi medici

GF Gensini

Roma 20 dicembre 2016

INNOVAZIONE

The ISDB is a forum for over 80 therapeutic journals

which are all independent of the pharmaceutical industry

the distinction between

bull genuine therapeutic advance and

bull mere innovation

were the driving force behind this ISDB Declaration

The term lsquoinnovationrsquo covers three concepts

bullThe commercial concept any newly marketed me-

too product new substances new indications

new formulations and new treatment methods

bullThe technology concept any industrial innovation

such as use of biotechnology or the introduction of

a new substance delivery system (patch spray

etc) selection of an isomer or a metabolite

bullThe concept of therapeutic advance a new

treatment that benefits the patient when compared to

previously existing options

ISDB Declaration on therapeutic advance - November 2001

Disponibile per iOS e Android

APP ndash Dispositivo medico certificato

wwwlaborsadelmedicoit

reg

La app laquoLa borsa del medicoraquo permette il

calcolo di score relativi a vari aspetti clinici

Il calcolo degli score egrave in alcuni casi legato ad

informazioni sulle possibili prescrizioni

terapeutiche secondo linee guida ufficiali

Impiego delle app come strumento di

supporto alle attivitagrave cliniche dei

sanitari

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 2: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

INNOVAZIONE

The ISDB is a forum for over 80 therapeutic journals

which are all independent of the pharmaceutical industry

the distinction between

bull genuine therapeutic advance and

bull mere innovation

were the driving force behind this ISDB Declaration

The term lsquoinnovationrsquo covers three concepts

bullThe commercial concept any newly marketed me-

too product new substances new indications

new formulations and new treatment methods

bullThe technology concept any industrial innovation

such as use of biotechnology or the introduction of

a new substance delivery system (patch spray

etc) selection of an isomer or a metabolite

bullThe concept of therapeutic advance a new

treatment that benefits the patient when compared to

previously existing options

ISDB Declaration on therapeutic advance - November 2001

Disponibile per iOS e Android

APP ndash Dispositivo medico certificato

wwwlaborsadelmedicoit

reg

La app laquoLa borsa del medicoraquo permette il

calcolo di score relativi a vari aspetti clinici

Il calcolo degli score egrave in alcuni casi legato ad

informazioni sulle possibili prescrizioni

terapeutiche secondo linee guida ufficiali

Impiego delle app come strumento di

supporto alle attivitagrave cliniche dei

sanitari

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 3: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

The term lsquoinnovationrsquo covers three concepts

bullThe commercial concept any newly marketed me-

too product new substances new indications

new formulations and new treatment methods

bullThe technology concept any industrial innovation

such as use of biotechnology or the introduction of

a new substance delivery system (patch spray

etc) selection of an isomer or a metabolite

bullThe concept of therapeutic advance a new

treatment that benefits the patient when compared to

previously existing options

ISDB Declaration on therapeutic advance - November 2001

Disponibile per iOS e Android

APP ndash Dispositivo medico certificato

wwwlaborsadelmedicoit

reg

La app laquoLa borsa del medicoraquo permette il

calcolo di score relativi a vari aspetti clinici

Il calcolo degli score egrave in alcuni casi legato ad

informazioni sulle possibili prescrizioni

terapeutiche secondo linee guida ufficiali

Impiego delle app come strumento di

supporto alle attivitagrave cliniche dei

sanitari

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 4: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Disponibile per iOS e Android

APP ndash Dispositivo medico certificato

wwwlaborsadelmedicoit

reg

La app laquoLa borsa del medicoraquo permette il

calcolo di score relativi a vari aspetti clinici

Il calcolo degli score egrave in alcuni casi legato ad

informazioni sulle possibili prescrizioni

terapeutiche secondo linee guida ufficiali

Impiego delle app come strumento di

supporto alle attivitagrave cliniche dei

sanitari

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 5: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

La app laquoLa borsa del medicoraquo permette il

calcolo di score relativi a vari aspetti clinici

Il calcolo degli score egrave in alcuni casi legato ad

informazioni sulle possibili prescrizioni

terapeutiche secondo linee guida ufficiali

Impiego delle app come strumento di

supporto alle attivitagrave cliniche dei

sanitari

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 6: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Vantaggi

Abbiamo chiesto a 6 medici volontari di effettuare un test di confronto tra il metodo

classico manuale e quello della APP laquoLa borsa del medicoraquo

Questi i risultati ottenuti

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 7: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

How to manage

Errors in blood transfusion

bullHydratation

bullEarly Ultrafiltration

bullEculizumab ()

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 8: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

1995

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 9: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 10: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Lrsquoinnovazione dirompentedistruttiva

hellip angioplasty was disruptive to open heart surgery just as drugs that lower cholesterol are

disruptive to angioplasty telemedicine to usual medicinehellip

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 11: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

This person does not exist

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 12: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

This person does not exist

This person does not exist HeShe is the average person of

EBM Evidence

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 13: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

EBM Groups and Individuals

bull Evidence comes from groups of patients Decisions are made by for individuals

bull Whatrsquos best on average must be best for each individual

D Kent Institute for Clinical Research and Health Policy Studies Tufts Medical Center

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 14: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

KaplanndashMeier Curves for Total Revascularizations

De Bruyne B et al N Engl J Med 20143711208-1217

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 15: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Conclusions

bull In patients with stable coronary artery disease FFR-guided PCI as compared with medical therapy alone improved the outcome

bull Patients without ischemia had a favorable outcome with medical therapy alone

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 16: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Public Health Regional Resolution

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 17: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Personalized Medicine

Stratified medicine

Systems Medicine

P4 Medicine

Narrative Medicine

Knowledge Based Medicine Translational Medicine

Patient Centered Care

Precision medicine

Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

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Heart Failure Facts bull The primary economical and social burden of HF syndrome is

hospitalization rate whose costs represent the highest ones ($40B per year in USA) within the entire health care management [1]

bull Approximately 80 of HF hospital admissions are driven by pulmonary congestion symptoms [23]

bull Almost 90 of acute decompensated HF patients after the admittance to the emergency department receive iv loop diuretic as the treatment of choice [4]

bull Despite therapy more than 50 of hospitalized patients for acute decompensated HF have little or no dyspnea improvement and weight loss after hospital discharge [235]

1 2014 American Heart Association Heart and Stroke Statistics 2 OConnor CM J Cardiac Fail 2005 11 200-205 3 Tavazzi L et al Eur Heart J 2006271207-1215 4 Wong YW he (ADHERE-EM) Am Heart J 2013 Aug166(2)349-56 doi 101016 5 Fonarow GC Rev Cardiovasc Med 20034 Suppl 7S21-30

Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

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come in

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Physiological Premise of IHM Guided Care

-21 -14 - 7 Days

Reactive Proactive

0

Symptoms

Pressure Changes

Heart Failure Event

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 20: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

CHAMPION Trial By Targeting Pressure Ranges and Titrating Medications Overall PAPs Can Be Reduced

Compared to the control group patients managed with PAP had persistently lower mean PA pressures over the treatment period

CHAMPION Trial PAP Mean Change from Baseline

Abraham WT et al Lancet 2011

PA

Me

an

Pre

as

ure

AU

C (

mm

Hg

-Da

ys

)

-220

-200

-180

-160

-140

-120

-100

-80

-60

-40

-20

0

20

40

60

80

100

Days from Implant

0 30 60 90 120 150 180

p = 00077

Treatment (-1557 mmHg-Days)Control (331 mmHg-Days)

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 21: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

cardioMEMS-CHAMPION trial

In 68 of cases Loop diuretic dose change

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 22: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

The Evolution of Pressure-Guided Therapy

Congestion is the limiting symptom

Symptoms and weights do not provide a reliable early warning system

Seeing is relieving

Events are associated with increased pulmonary pressures

HF preserved EF is more the same than different

Treating the peaks is not enough to prevent events

Reduce not just peaks but also the plateau

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 23: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Does CHAMPION duplicate what can be seen by measuring electrical Intra-thoracic Impedance (ITI)

bull Remote of assessment of ITI is now currently provided by innovative technology embedded in implantable defibrillators (ICD and CRT D devices)

bull The OPTIVOL ITI detection system has been developed by MEDTRONIC and has been widely tested to prove efficacy of intra-thoracic impedance decline to manage pending acute decompensated HF

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 24: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Intrathoracic impedance measurement by implantable system

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 25: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Algorithm performance on validation data set

Cheuk-Man Yu et al Circulation 2005112841-848

Copyright copy American Heart Association Inc All rights reserved

For validation data set nominal threshold of 60 Ωd resulted in

sensitivity of 769 and false-positive rate of 15 false-

positives per patient-year of monitoring as highlighted by

circle

15

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 26: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

The OPTIVOL fluid index pivotal trials van Veldhuisen D et al Circulation 2011 DOT HF

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 27: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

The OPTIVOL fluid index pivotal trials Bohm M et al et al EHJ 2015 OPTILINK

Patients with potentially higher risk of cardiac decompensationdeterioration presenting at least 1 out of 4 criteria

bull HF-related Hospitalization within the last 12 months bull IV-Oral Diuretic Treatment within last 30 days bull Increased BNP within last 30 daysgt 400pgml bull Increased NT-pro-BNP within last 30 days [gt 400 pgml (lt 50 yrs) gt 900 pgml (50-75 yrs) gt 1800 pgml (gt 75 yrs)]

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 28: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

Intra-thoracic Impedance Limitations

bull The OptiVol find can be insensitive in chronically volume overloaded patients or when volume accumulation occurs very slowly

bull In the case the reference impedance also changes it prevent separation to occur between reference and measured impedance and than it prevent the calculated cumulative sum to rise

Zile M et al Circulation Heart Failure 2016

1924hellipTelemedicine (radiomedicine)

come in

Page 29: Innovazione nel settore dei dispositivi medici€¦ · INNOVAZIONE ? The ISDB is a forum for over 80 therapeutic journals which are all independent of the pharmaceutical industry

1924hellipTelemedicine (radiomedicine)

come in