THE FUTURE ICD IS NOW Advances in Science and Learning

Transcription

1 THE FUTURE ICD IS NOW Advances in Science and Learning Martin C. Burke DO Chief Scientific Officer CorVita Science Foundation CORVITA SCIENCE FOUNDATION 1, ACADEMIC MEDICAL CENTER; UNIVERSITY OF AMSTERDAM; NETHERLANDS 2 San Antonio, TX 2017

2 COI DISCLOSURES I have received lecture and proctoring honoraria from Spectranetics. I have been funded by and NIH/SBIR grant to AJ Medical Devices, Inc. (AJMD) and research grants from Boston Scientific, Medtronic, St. Jude Medical, Guidant, Inc. and Cameron Health, Inc. I am or have been a consultant to AJMD, Boston Scientific and Cameron Health. I have an equity stake in AtaCor Medical, Inc. and am Chief Medical Officer.

3 ICD therapy is well established and successful, but still associated with complications Cumulative incidence complications in Danish registry Re-operations in NCDR ICD Registry Single Chamber ICD 15.5% re-operation at 6 yrs Dual Chamber ICD CRT-D N = 5918 N = % primary prevention R.E. Kirkfeldt et al. Eur Heart J 2014 Ranasinghe. AHA 2014 Abstract 20158

4 Transvenous lead related complications associated with significant morbidity and mortality Mortality after TV lead infection / extraction 10% 1-yr mortality 32% 1-yr mortality Tarakji KG et al Europace 2014

5 An Entirely Subcutaneous ICD SIMULTANEOUS 3-LEAD ECG LEAD I RA LA 14 cm 14 cm LEAD II LEAD III LL Peak Zones 1. RECORD: Supine+Standing 25 mm/s, 5-20 mm/mv 2. SELECT t QRS pea

6 S-ICD System Components: Q-TRAK Electrode 4 connections to coil (2 distal / 2 proximal) Cable core design (distal sense connection) Proximal Sense Ring

7 COMPARE TRIAL Position 1A Position 2 Position 3 Position 4 Position 5 Position 6 Position 1B Burke et al. HRJ 2009 (abstr)

8 COMPARE TRIAL Surface ECG with BPC COMPARE (All Data, n = 247) QRS & T-wave Amplitude (mv) QRS:T-wave Ratio (QRS/T) A 1B A 1B A 1B AC Postures BC Postures AB Postures 0 Burke et al. HRJ 2009 (abstr)

9 TWOS Algorithm -Essentially treats repetitive TWOS as bigeminy -The Algorithm is functional in all zones not just the conditional zone. -It has a significant benefit in decreasing TWOS in ambulatory human event library -The algorithm does not inhibit TTT or affect sensitivity for ventricular arrhythmias Brisben, Burke et al. JCE 2015

10 SMART Pass algorithm Enables a high-pass filter (9 Hz) for sensing and heart rate estimate. ECG for rhythm discrimination remains unchanged and continues to use the wide-band filtered ECG similar to previous generations. Enabled with manual/automatic setup during a session. Automatically disabled for low amplitudes and slower rates. Theuns, Burke et al. HRJ 2016 Abstr.

11 9 Hz Filter OFF/ON

12 Patients Oversensing, Cardiac Gen 1 Gen 2 Gen 2.5 Oversensing, Noncardiac (e.g., EMI) Inappropriate for AF/SVT Results EFFORTLESS VT/VF Appropriate Episodes Patients (Pct Reduction) 0 Oversensing, Cardiac Gen 1 Gen 2 Gen 2.5 Oversensing, Noncardiac Inappropriate for AF/SVT Episodes (Pct Reduction) VT/VF Appropriate Gen 2 vs Gen 1 Gen 2.5 vs Gen 1 Gen 2 vs Gen 1 Gen 2.5 vs Gen 1 Oversensing, Cardiac 29.3% 70.7% 36.1% 83.1% Oversensing, Non-cardiac (e.g., EMI) 45.0% 70.0% 50.0% 72.2% Inappropriate AF/SVT 7.7% 0.0% 10.5% 5.3% Total Inappropriate 28.6% 57.1% 36.0% 69.8% VT/VF Appropriate 6.7% 6.7% 2.3% 5.8% Theuns, Burke et al. HRJ 2016 Abstr.

13 S-ICD Pooled Results Mortality Compared to TV-ICD Studies S-ICD had a 2 year mortality rate that compared favorably with mortality rates in studies with TV-ICDs Study Mortality (At 2 years) Average Age 1 0 Prevention Ischemic NYHA LVEF S-ICD Pooled* 3.2% 50 70% 38% 37.5% class II-IV 39% MADIT RIT 1 5-7% High rate and Delayed Therapy Arms % 53% 98% class II or III 26% SIMPLE 2 11% 64 70% 63% class II or III 32% The 1.6% annual mortality rate with the S-ICD was deemed provocative by the authors as it is lower than observed in TV-ICD studies. *This analysis was not designed or powered to assess mortality and care should be taken as the population in this analysis may differ from the patient population in TV-ICD studies. 1 Burke MC et al. Pooled Analysis of the EFFORTLESS and IDE Registry. JACC April 20 th Moss AJ et al. MADIT RIT Study NEJM 2012;367; Healy JS et al. SIMPLE Study Heart Rhythm 2014;LBCT01;LB01-01.

14 Boersma, Burke et al. 2015, Heart Rhythm Journal Mortality following Extraction and Re-implant with S-ICD

15 Percentage of CRT Qualifiers Heart Failure Society Database

16 Majority of 1 st time ICD recipients were candidates for an S-ICD based on lack of bradycardia of CRT indications Close to 55% of 1 st time ICD recipients were eligible for an S-ICD based on their lack of bradycardia or CRT indications (n=123,763) 1 Friedman, D.J., et al., Trends and In-Hospital Outcomes Associated With Adoption of the Subcutaneous Implantable Cardioverter Defibrillator in the United States. JAMA Cardiol, Published online September 07, doi: /jamacardio

17 Why did the authors conclude that S-ICD should be considered in all eligible patients? Low complication rate and high rates of successful DFT with S-ICD despite use in high risk patients 1 A propensity matched analysis showed that in hospital complication rates were similar among patients with S-ICD and TV-ICD 1 1 Friedman, D.J., et al., Trends and In-Hospital Outcomes Associated With Adoption of the Subcutaneous Implantable Cardioverter Defibrillator in the United States. JAMA Cardiol, Published online September 07, doi: /jamacardio

18 Performance of the subcutaneous implantable cardioverter defibrillator in primary prevention patients Lucas V. A. Boersma, MD, PhD, Craig S. Barr, MD, Martin Burke, DO, Angel R. Leon, MD, Dominic A. Theuns, PhD, John M. Herre, MD, Raul Weiss, MD, Mayer Rashtian, MD, FACS, Mark S. Kremers, MD, Petr Neuzil, MD, PhD, Michael P. Husby, MS, Nathan Carter, MS, Tim Stivland and Michael R. Gold, MD, PhD. St. Antonius Ziekenhuis, Nieuwegein, Netherlands, Russells Hall Hospital, Dudley, United Kingdom, University of Chicago Hospitals, Chicago, IL, Emory University, Atlanta, GA, Erasmus MC, Rotterdam, Netherlands, Cardiology Consultants, Ltd., Norfolk, VA, Ohio State University Medical Center - Div. of Cardiovascular Medicine, Columbus, OH, Foothill Cardiology, Pasadena, CA, Novant Heart and Vascular Institute, Charlotte, NC, Na Homolce Hospital, Prague 5, Czech Republic, Boston Scientific, St Paul, MN, Medical University of South Carolina, Charleston, SC Heart Rhythm Journal

19 Group Breakdown and Follow-up Follow-up of Implanted Patients Secondary Prevention n=247 PP- no EF PPpEF n=147 PPrEF n=377 Primary Prevention N=599 Secondary Prevention Primary Prevention n Implant Duration (Days) Mean Range [2-1542] [3-1527] PPrEF [ ] PPpEF [3-1514] Heart Rhythm Journal

20 SP and PP by Etiology Heart Rhythm Journal SP 12% 15% 33% 2% 38% Hypertrophic Infiltrative Arrhythmic Ischemic 6% Non-Ischemic Other 37% PPpEF 16% 0.7% 40% PP 28% 1% 12% 19% 1% PPrEF 34% 0.3% 2% 41% 62% PPrEF predominantly (non-)ischemic CMP

21 PP vs SP Complications PPrEF vs PPpEF Primary # at Risk (%) Secondary # at Risk (%) PPrEF # at Risk (%) PPpEF # at Risk (%) Complications occur early, during and after implant Rates are low and consistent across groups Heart Rhythm Journal

22 PP vs SP Inappropriate Shocks PPrEF vs PPpEF PP Dual Zone # at Risk (%) PP Single Zone # at Risk (%) SP Dual Zone # at Risk (%) SP- Single Zone # at Risk (%) PPrEF Dual # at Risk (%) PPrEF Single # at Risk (%) PPpEF Dual # at Risk (%) PPpEF Single # at Risk (%) Independent of PP or SP indication or etiology Heart Rhythm Journal Inappropriate shock lower by dual zone programming

23 Appropriate Therapy for VT/VF PP vs SP PPrEF vs PPpEF Primary Prevention Secondary Prevention Primary # at Risk (%) Secondary # at Risk (%) PPrEF # at Risk (%) PPpEF # at Risk (%) SP pts more need for appropriate therapy than PP pts PPrEF more need for appropriate therapy than PPpEF Heart Rhythm Journal

24 PP vs SP Mortality PPrEF vs PPpEF PPpEF PPrEF PPpEF PPrEF Primary # at Risk (%) Secondary # at Risk (%) PPrEF # at Risk (%) PPpEF # at Risk (%) Heart Rhythm Journal Mortality was low for all indications and etiologies Mortality was highest in the PPrEF group (3.0%/year)

25 Real World Experience with the Subcutaneous ICD in the United States: The S-ICD Post-Market Approval Study Michael R Gold MD, PhD, Johan D. Aasbo, DO, FHRS, Mikhael F. El-Chami, MD, FHRS, Mark Niebauer, MD, PhD, FHRS, John Herre, MD, Jordan M. Prutkin, MD, FHRS, Bradley P. Knight, MD, FHRS, Steven Kutalek, MD, FHRS, Kevin Hsu, MD, FHRS, Raul Weiss, MD, FHRS, Eric Bass, Michael Husby, MS, MPH, Timothy M. Stivland, MBA, Martin C. Burke, DO and all PAS investigators Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

26 % of Respondents Reasons for S-ICD Device Choice (N=1637, multiple reasons could be chosen) S-ICD or TV-ICD was suitable 91.2% S-ICD was only option 8.8% Patient preference Age Activity Prior TV-ICD Infect/Mal CKD / Dialysis Infection Risk Adverse anatomy 1.3 Infection risk Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

27 Alternate Screening Results Available Sensing Vectors ECG Screening Success*: One vector 100.0% Two vectors 93.8% Three vectors 51.4% Vector Suitability: Primary vector 82.6% Secondary vector 86.7% Alternate vector 61.7% * Success requires passing in the supine and standing positions. For inclusion in the registry at least one of three vectors was required to pass the screening test. Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

28 Percent Patient Demographics Characteristic Mean or % Age 53.2 ± 15.0 Gender (Male) 68.6% African American 28.2% BMI (kg/m 2 ) 29.8 ± AGE DISTRIBUTION Age Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

29 Patient Baseline Disease Characteristics Cardiac Disease and Procedure History Percent Cardiac History Myocardial Infarction 33.2% Cardiac Arrest 15.4% Left Ventricular EF, mean 32±15% Primary Prevention 76.7% Primary Prevention with EF % Inherited Disorders 5.0% Procedure History CABG or Valve Surgery 20.6% Pacemaker 2.7% Previous ICD 12.9% Co-Morbidities Percent Heart Failure 74.0% Hypertension 61.6% Atrial Fibrillation 16.2% Diabetes 33.6% Kidney Disease 25.6% Hemodialysis 13.4% Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

30 Baseline Disease Characteristics S-ICD Study Comparison S-ICD PAS EFFORTLESS Region US Primarily EU Patients Age 53.2 ± ± 18 Male 68.6% 72% EF 32.0 ± 14.6% 42 ±19% Primary Prevention 76.7% 63% Heart Failure 74.0% 29% Hypertension 61.6% 24% Diabetes 33.6% 12% Kidney Disease 25.6% 9% Previous ICD 12.9% 15% S-ICD PAS study cohort represents a sicker population with more comorbidities. Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

31 Programming Characteristics Programming Characteristic Percent Dual zone programming 97.2% Shock zone 200 bpm 99.9% Conditional zone 200 bpm 76.9% Chosen sensing vectors Primary 53.6% Secondary 35.9% Alternate 10.5% Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

32 Implant Procedure Characteristics Implant Procedure Mean or % Two incision technique 52.2% Anesthesia General anesthesia 64.1% Conscious sedation 35.8% Use of Imaging 65.1% Procedure Time (Incision to closure; minutes) 77.3 ± 36.2 Repositioning during implant 2.8% Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

33 30-Day Complications Complication-Free Rate = 96.2% VARIABLE Odds Ratio ± 95% CI Odds Ratio (95% CI) P-value Age (years) 0.98 ( ) Female African American Height (in) BMI kg/m 2 Ejection Fraction Myocardial Infarction NYHA II/III/IV Diabetes Dialysis at baseline 1.79 ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) Predictors of Complications by Multivariate Modeling: Younger Age Higher BMI Diabetes Prior TV Extraction 1.91 ( ) Antiplatelet/Anticoagulation 1.86 ( ) Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

34 Cause of Complications 30-day Complication Type All Patients (%) S-ICD System Infection 1.2 Hematoma 0.4 Sub-optimal Electrode Position 0.4 Unable to Convert During Procedure 0.4 Inappropriate Shock: Oversensing 0.2 Inadequate Healing of Incision Site 0.1 Incisional/Superficial Infection 0.1 Pulse Generator Movement / Revision 0.1 Pulse Generator Related Discomfort 0.1 Other (events that occurred 1 patient) 0.7 Complications Total 3.7% Heart Rhythm May 11. pii: S (17) doi: /j.hrthm

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36 EMBLEM MRI S-ICD System is ImageReady EMBLEM MRI S-ICD System provides full-body MRconditional scan capabilities for a 1.5T environment *21,22 * When conditions of use are met 1.5T MR-Conditional Automatic MRI Timeout Mode No exclusions zone No time limitations during MRI scan 21,22 No patient restrictions Simple programmer interface Dedicated MRI report for clinic documentation MRI mode viewable on LATITUDE Updated MR-conditional label for EMBLEM S-ICD System with any S-ICD electrode

37 Moore s Law in healthcare

38 Application of S-ICD is limited due to lack of pacing capability Bradypacing: Limited evidence of S-ICD with LCP & TV-Pacers Anti-tachy pacing: No solution Substantial ICD subgroup benefits from ATP therapy Prospective registry data from single center in Germany N =1398 Tjong et al. Europace 2016 Kleemann et al. Europace 2015

39 mcrm TM System Components Prototypes of EMBLEM* and EMPOWER* mcrm Systems* Implantable Device Prototypes Programmer Prototypes BSC 3300 LATITUDE Programming System EMPOWER Delivery and Retrieval Prototypes Preloaded delivery catheter with extendable inner catheter EMPOWER Modular Pacing System EMBLEM Family of S-ICDs EMPOWER Prototype Details 31.9 mm x 6 mm 0.9 cc Active fixation talons Tether / Snare port Dedicated delivery and retrieval catheters *mcrm Systems, EMBLEM S-ICD mcrm functionality, and EMPOWER Modular Pacing Systems are in development and not approved for sale in any geography.

40 Modular CRM Systems (mcrm TM) mcrm Systems designed to deliver pacing and ATP in coordination TV-ICD S-ICD mcrm TM System* EMBLEM TM S-ICD* EMPOWER TM Modular Pacing System* Documented need for Pacing or ATP Potential need for Pacing or ATP No need for Pacing or ATP 2016 Boston Scientific Corporation or its affiliates. All rights reserved. *mcrm Systems, EMBLEM S-ICD mcrm functionality, and EMPOWER Modular Pacing Systems are in development and not approved for sale in any geography. CRM AA MAY2016

41 Modular Devices/Medical Body Network Tjong, Burke et al. JACC 2016

42 Tissue Encapsulation Images 90-Day Canine Example 90-Day Ovine Example

43 Extracting Leadless Pacing Devices Is Desired Preload Cardiac Output = Heart Rate X Stroke Volume Afterload Contractility Braunwald 5 th edition, adapted Factors Affecting Cardiac Output

44 Retrieval Overview

45 IEEE, 2008 Need More Power: Battery Technology

46 How does an MBAN system operate? A typical MBAN consists of: a master programmer/control transmitter ( hub device ), one or more client transmitters ( body sensors ), which are worn on the body and only transmit while maintaining communication with the hub that controls the transmissions. The hub conveys data messages to the body-worn sensors to specify, for example, the transmit frequency that should be used. The hub and sensor devices will transmit in the MHz band. IEEE, 2008

47 Individual Intelligence Courtesy of St Jude Medical Personalized Physiology Analytics T H E F I R S T O F I T S K I N D I N H E A LT H C A R E. Gary Conkright, Cofounder/CEO, physiq October 2, 2015

48 Some Modules Need A Mother Ship

49 Individual Patterns: Normal and Abnormal

50 Individual Patterns: Normal and Abnormal

51 Multisensor Algorithm Diagnostics in ICDs and CRT-Ds with associated remote monitoring systems may provide an opportunity to better identify worsening status, but technology to date has used single sensors with high false-detection rates or required manual review of multiple measures, limiting utility and adoption. 1 New approach seeks to use new device sensors to emulate what physicians do in their clinical assessment - evaluate multiple signs and symptoms 2 and utilize multiple diagnostics in ambulatory evaluation. New + existing biometric sensors in ICD and CRT-D Automatically evaluate signs & symptoms of Heart Failure Elevated filling pressure Tachypnea Dyspnea on exertion Dyspnea at rest Fluid accumulation and Pulmonary edema Orthopnea or Paroxysmal Nocturnal Dyspnea Atrial fibrillation Tachycardia Automated, ambulatory heart failure status indicator available remotely or inclinic 1 Conraads VM et al., Eur Heart J, 2011:32(18), Heart Failure Practice Guideline, Journal of Cardiac Failure, 2010:16(6),e137

52 MultiSENSE Trial: Design International, multi-center, non-randomized, clinical study designed to develop and prospectively evaluate a multi-sensor index and alert for the early detection of worsening heart failure Key inclusion criteria Age 18 or above Currently implanted with a COGNIS CRT-D system NYHA Class II, III or IV within the last 6 months Key exclusion criteria Documented as pacemaker dependent A history of appropriate tachycardia therapy within 1 week prior to enrollment Likely to undergo lead or PG revision Subjects that have received a heart or lung transplant Receiving mechanical circulatory transplant A life expectancy of less than 12 months 1 Boehmer JP et al. JACC:Heart Failure 2017(5):3;

53 MultiSENSE Trial: Design Endpoint 1: Sensitivity for detecting usable heart failure events >40%. An exact two-sided 95% confidence interval (CI) for the sensitivity calculated based on the binomial distribution and the lower bound tested against a performance goal of 40%. Endpoint 2: Unexplained alert rate (UAR) per patient year <2.0 A two-sided 95% CI for the unexplained alert rate calculated based on the negative binomial distribution and the upper bound tested against the performance goal of Boehmer JP et al. JACC:Heart Failure 2017(5):3;

54 MultiSENSE Trial: Results Primary Endpoints Met Sensitivity = 70% [ %] Unexplained Alert Rate = 1.47 [ ] Median Time to HFEs 34 days FPR = 1.56 [ ] 1 Boehmer JP et al. JACC:Heart Failure 2017(5):3;216-25

55 HeartLogic* Index Trends Median Time from Alert Onset to HFEs was 34 days Index Leading to Heart Failure Event, Mean ± SEM Non-Event Patient Index, Mean ± SEM Event day or last available index date * p<0.05; rank sum test; days -180 to Boehmer JP et al. JACC:Heart Failure 2017(5):3;216-25