Non-invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic - PowerPoint PPT Presentation

Non-invasive Lung IMPEDANCE-Guided Preemptive Treatment in Chronic Heart Failure Patients: a Randomized Controlled Trial (IMPEDANCE-HF trial) Michael Kleiner Shochat, MD, BSc, PhD a , Avraham Shotan, MD a , David S Blondheim, MD a , Mark Kazatsker, MD a , Iris Dahan, MSIT a , Aya Asif, MD a , Yoseph Rozenman, MD b , Ilia Kleiner, MD c , Jean Marc Weinstein, MBBS, FRCP c , Aaron Frimerman, MD a , Lubov Vasilenko, MD a , Simcha R Meisel, MD, MSc a a Heart Institute, Hillel Yaffe Medical Center, Hadera, Rappaport School of Medicine, Technion, Haifa, Israel; b Cardiovascular Institute, Wolfson Medical Center, Holon, Sackler Faculty of Medicine, Tel-Aviv University, Israel, c Cardiology Department, Soroka University Medical Center, Beer Sheva. American College of Cardiology. Chicago. Late Braking Clinical Trial Session. Apr.04. 2016 Presenter - Michael Kleiner Shochat Conflict of interest: Michael Kleiner Shochat is a co-founder and member of the board of directors of the RSMM Company that manufactured and supplied the devices for the study.

A i m : Our trial was performed to evaluate the hypothesis that- Lung impedance-guided treatment reduces hospitaliza5ons for Acute Heart Failure. Inclusion criteria - Chronic Heart Failure patients Left Ventricle Ejection Fraction ≤ 35% New York Heart Association class II-IV

P r o c e s s O f L u n g F l u i d A c c u m u l a t i o n Stable stage - There is no fluid accumulation in lung 3 STAGES OF Lung fluid accumulation - without clinical signs HEART FAILURE: Dramatic deterioration in patient’s condition & urgent hospitalization Current point where treatment starts Ideal point to start preemptive treatment

Tr a ditiona l Te c hnologie s VS R SMM Te c hnology EGM Traditional Impedance Technique TTI TTI

The Objective: Accurately Identifying the Lung Impedance (LI) Value Chest Wall Impedance 1 + Lung Impedance + Chest Wall Impedance 2 Transthoracic Impedance A-B ( TTI AB ) = Chest Wall Impedance ( CWI ) is NOISE Impedance A CWI 1 Ω X500~ The Challenge : Identifying small changes in the Lung Impedance as 1-3 Ω from the total TTI as 1050 Ω Impossible Target Organ LI Ω X50~ The Solution : Elimination NOISE Chest Wall Impedance (500 Ω +500 Ω ) from Transthoracic Impedance (1050 Ω ) makes identification small changes in the Lung Impedance CWI 2 Ω X500~ Possible . B

Study design: Randomized, single blinded, two centers. Study population. Mean age in both groups 67 y. Men – 80%. Efficacy endpoints. Both groups were well adjusted by baseline pa/ent characteris/cs, baseline medica/ons One year before randomiza/on and parameters of physical examina/on. Randomiza/on Monitoring Group (N=128). Mean = 48 m. FU Future Monitoring Group HF hospitaliza/ons = 1.2/ pa/ents year 1 y 2 y 3 y 4 y 5 y 6 y 7 y 8 y Run in period (3m) for adjustment Future Control Group maximally possible guidelines Control Group (N=128). Mean = 39 m. FU HF hospitaliza/ons = 1.1/ recommended drug doses for CHF treatment. pa/ents year Primary efficacy endpoints: 1. Acute heart failure hospitaliza/ons up to 12 months. 2 . Acute heart failure hospitaliza/ons during en/re follow up Secondary efficacy endpoints: 1. All –cause, Cardiac hospitaliza/ons during en/re follow up . 2 . All-cause, Cardiac and Heart Failure mortality during en/re follow up.

S t r a t e g y o f d r u g a d j u s t m e n t ∆LIR Baseline (dry) lung impedance (BLI). As if pa/ent is 0% healthy. Pa5ent ’ s status is very stable. -5% No or very small inters55al conges5on. -10% NYHA class I – II. No need in addi5onal -15% treatment. -18% -20% Target zone for adjustment treatment Pa5ents became more congested but s5ll no more complains -24% Beginning Heart Failure hospitaliza/ons -25% -30% -35% -40% Increasing in conges5ons Hospitaliza5ons for Heart Failure Increased risk of Heart Failure hospitaliza5ons -45% -50% -55% (ΔLIR) = [current LI/BLI)-1]

Results R a t e o f H e a r t F a i l u r e h o s p i t a l i z a t i o n s ( p e r p a t i e n t * y e a r ) P < 0.001 1 year 2 year 3 year 4 year 5 year 6 year 7 year 8 year Lung Impedance-guided treatment group Follow up period Control group treated by clinical assessment

R e s u l t s H o s p i t a l i z a t i o n s Number of hospitaliza5ons Number of hospitaliza5ons Number of hospitaliza5ons P < 0.0001 P < 0.0001 P < 0.0001 52% reduc5on in cardiac 39% reduc5on in all-cause 56% reduc5on in cardiac hospitaliza5ons during hospitaliza5ons during en5re hospitaliza5ons during en5re period of follow up period of follow up en5re period of follow up Follow Up period Follow Up period Follow Up period Cardiac Hospitaliza=ons Heart Failure Hospitaliza=ons All-cause Hospitaliza=ons Method of sta=s=cs: Cox regression analyses

R e s u l t s Mortality 43% reduc5on in all-cause 62% reduc5on in Heart 55% reduc5on in cardiac deaths during en5re period Failure deaths during deaths during en5re P < 0.001 P < 0.001 P < 0.001 of follow up en5re period of follow up period of follow up Follow Up period Follow Up period Follow Up period Heart Failure death All-cause Death Cardiac Death Method of sta=s=cs: Kaplan Meyer analyses

R e s u l t s ∆LIR Linear mixed effects regression model was used to evaluate P < 0.001 differences between ∆ LIR into and between groups. Monitored Group Follow Up period Difference in pulmonary conges=on Control Group between groups during follow up period

T A B L E Drug modifications during entire follow up Medications Monitored Group Control Group p Monitoring /Control group. Ratio of drug adjustment Rate of changes in medical therapy Total 3166 (6.2)† 1244 (3.0)† <0.05 2.1 times Diuretics 1530 (48%)‡ 515 (42%)‡ <0.05 Diuretics 1530 (3.0)† 515 (1.3)† <0.05 2.3 times Beta Blockers 792 (25%)‡ 303 (24%)‡ <0.05 Beta Blockers 792 (1.6)† 303 (0.7)† <0.05 2.3 times ACE inh /ARB 410 (13%)‡ 142 (11%)‡ <0.05 ACE inh /ARB 410 (0.8)† 142 (0.3)† <0.05 2.7 times Nitrates 166 (5%)‡ 78 (6%)‡ <0.05 Nitrates 166 (0.3)† 78 (0.2)† <0.05 1.5 times MRA 154 (5%)‡ 144 (12%)‡ NS MRA 154 (0.3)† 144 (0.4)† NS 0.9 times Digoxin 114 (4%)‡ 62 (5%)‡ <0.05 Digoxin 114 (0.2)† 62 (0.15)† <0.05 1.5 times

C o n c l u s i o n s Data of “IMPEDANCE-HF” trial shows that Lung Impedance guided treatment in compare with treatment based on clinical assessment of HFrEF patients: Hospitaliza5ons (Primary endpoint) 1. Reduces rate of HF hospitaliza=ons during first year by 58%. 2. Reduces rate of HF hospitaliza=ons during 4 years by 56%. Hospitaliza5ons (Secondary endpoint) 3. Reduces rate of all-cause hospitalizations during 4 years by 39%. 4. Reduces rate of cardiac hospitalization during 4 years by 52%. 5. Reduces rate of Non-cardiac hospitalization during 4 years by 9%, (p=0.6). Deaths (Secondary endpoint) 7. Reduces rate of All-cause mortality during 4 years by 43%. 8. Reduces rate of Cardiac mortality during 4 years by 55%. 9. Reduces rate of Heart Failure mortality during 4 years by 62%. 10. No changes in Non-cardiac mortality during 4 years .

These results support Non-invasive Lung Impedance technology is enough sensi5ve to detect a very early stage of evolving pulmonary conges5on and Lung Impedance-guided treatment is reliable for improving hospitaliza5on and survival of Heart Failure pa5ents. Thank you very much for aYen/on!