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Newer and Future (Device) Therapies for Heart Failure

Newer and Future (Device) Therapies for Heart Failure. William T. Abraham, MD, FACP, FACC, FAHA, FESC Professor of Medicine, Physiology, and Cell Biology Chair of Excellence in Cardiovascular Medicine Chief, Division of Cardiovascular Medicine

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Newer and Future (Device) Therapies for Heart Failure

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  1. Newer and Future (Device) Therapies for Heart Failure William T. Abraham, MD, FACP, FACC, FAHA, FESC Professor of Medicine, Physiology, and Cell Biology Chair of Excellence in Cardiovascular Medicine Chief, Division of Cardiovascular Medicine Deputy Director, Davis Heart & Lung Research Institute The Ohio State University Columbus, Ohio Dr. Abraham has received consulting fees and/or research grants from Abbott Vascular, Cardiokinetix Inc., CardioMEMS, CVRx, Impulse Dynamics, Medtronic, and St. Jude Medical, and Sunshine Heart.

  2. Current Evidence-Based Treatment of Chronic Systolic Heart Failure Control Volume Reduce Mortality Aldosterone Antagonist or ARB ACEI or ARB Diuretics -Blocker CRT  an ICD* Hyd/ISDN* Treat Residual Symptoms Digoxin *For all indicated patients. Abraham WT, 2005.

  3. Current Evidence-Based Treatment of Chronic Diastolic Heart Failure

  4. Guideline Recommendations* for the Management of Diastolic Heart Failure • Recommended Therapies for Routine Use: • Treating known risk factors (e.g., hypertension) with therapy consistent with contemporary guidelines • Ventricular rate control for all patients with AF • Drugs for all patients • Diuretics • Drugs for appropriate patients • ACEI • ARBs • Beta-Blockers • Digitalis • Coronary revascularization in selected patients • Restoration/maintenance of sinus rhythm in appropriate patients *From ACC/AHA and HFSA heart failure guidelines; All of these recommendations based on consensus

  5. Despite Current Therapies, Heart Failure Morbidity and Mortality Remain High • 30% to 40% of patients are in NYHA class III or IV • Re-hospitalization rates • 2% at 2 days • 25% at 1 month • 50% at 6 months • 5-year mortality ranges from 15% to more than 50% • Asymptomatic LVD  15% • Mild-moderate HF  35% • Advanced HF >50%

  6. Devices Under Investigation for the Treatment of Heart Failure • Cardiac Contractility Modulation • Cardiac Support Devices • Ventricular Partitioning Devices • Percutaneous Valve Repair • Continuous Positive Airway Pressure Breathing (including ASV) • Transthoracic Phrenic Nerve Pacing • Ultrafiltration Devices

  7. Devices Under Investigation for the Treatment of Heart Failure • Newer Counter-pulsation Technologies • Second and Third Generation LVADs • Percutaneously-applied Ventricular Assistance • Totally Implantable Artificial Hearts • Fluid Monitors • Implantable Hemodynamic Monitors • Many others

  8. Cardiac Contractility Modulation (CCM) CCM Duration Delay Muscle Force Amplitude Apply electric signal during absolute refractory period Detect local activation

  9. Optimizer II System

  10. Early Studies of CCM • Preclinical and early clinical studies showed that CCM: • Increases cardiac contractility • Reduces myocardial work • Produces LV reverse remodeling • Induces molecular changes (in genes, proteins and phosphorylation) indicative of improved calcium handling and contractile function • These observations led to pivotal trials in Europe (FIX-HF-4) and the U.S. (Fix-HF-5)

  11. Results of the FIX-HF-4 and FIX-HF-5 Studies • In NYHA class III-IV heart failure patients, CCM improves • Exercise capacity • Quality of Life (MLWHFQ score) • NYHA • A subgroup of patients (EF ≥ 25, NYHA III) appears to benefit most from CCM* • A prospective randomized controlled trial to confirm these observations (FIX-HF-5b) is ongoing in the U.S. *Abraham WT, et al. J Cardiac Failure 2011

  12. Baroreflex Activation Lead Implantable Pulse Generator Baroreflex Activation Therapy (BAT) Carotid Baroreceptor Stimulation Brain Autonomic Nervous System Inhibited Sympathetic Activity Enhanced Parasympathetic Activity Heart Vessels Kidneys ↓ HR ↑ Vasodilation↓ Stiffness ↑ Diuresis ↓ Renin secretion Reduced blood pressureReduced afterload, wave reflections and augmentation Reduced myocardial work and oxygen consumptionReduced neurohormonal stimulus Increased venous capacitance

  13. Response to BAT is Prompt andDose-Related ~ 4 min

  14. BAT for Heart Failure Heart failure shares similar underlying mechanisms and drug treatments with hypertension BAT technology will be applied in the same way to treat heart failure patients Initial studies targeting heart failure with preserved LVEF • Drugs + Devices  Drugs • No Approved Therapies Low EF Preserved EF 5.8 Million Heart Failure Patients in U.S.

  15. HOPE-4-HF Study Overview Implant/Activate Rheos + Medical Management Randomize 2:1 Medical Management Only First Phase Second Phase ≤ 100 patients at 15 sites FDA review on 30 Rheos patients followed for 3 mo 540 patients at 70 U.S. sites and20 OUS sites Primary endpoint: CV death / HF event Follow-up until 270 primary endpointevents reached Enrollment uninterrupted Data counts toward endpoint

  16. Spinal Cord Stimulation forHeart Failure • SCS is approved for the treatment of chronic pain syndromes and has been used to treat intractable angina pectoris • Current evidence suggests that thoracic SCS decreases sympathetic tone • In a canine model, SCS caused vagal-like responses by slowing sinus rate and prolonging AV nodal conduction time and ventricular refractory period • These effects may be beneficial in chronic heart failure

  17. Clinical Response to SCS in a Canine Model of Heart Failure Lopshire JC, et al. Circulation 2009

  18. Echocardiographic Response to SCS in a Canine Model of Heart Failure Lopshire JC, et al. Circulation 2009

  19. Transvenous Phrenic Nerve Stimulation • Respiratory Rhythm Management • Unilateral phrenic nerve stimulation of the diaphragm • Implantable stimulator with proprietary algorithm • Implantable proprietary transvenous leads • Stimulation algorithm restores natural breathing pattern, stabilizes gas exchange and decreases hypoxic episodes • Inserted by cardiologist or EP using techniques similar to existing cardiac devices • Currently stand-alone device, but can be combined with other cardiac therapies With Therapy

  20. Acute Respiratory Rhythm Management Improves Sleep Indices Central Apnea Index Apnea Hypopnea Index % change = -91.0 p<0.0001* % change = -49.0 p=0.0006* *t-test *t-test Oxygen Desaturation Index 4% ODI 4 (%) Arousal Index % change = - 55.0 p=0.001* % change = -51.0 p=0.0005* *t-test *t-test Ponikowski P, ….. Abraham WT. Eur Heart J 2011

  21. Implantable Hemodynamic Monitors LV Pressure Sensor RV Pressure Sensors PA Pressure Sensors LA Pressure Sensor

  22. MEMS-based pressure sensor Home electronics PA Measurement database The Pulmonary Artery Pressure Measurement System Catheter-based delivery system

  23. CHAMPION Trial: Cumulative HF Hospitalizations Over Entire Randomized Follow-Up Period p < 0.001, based on Negative Binomial Regression Cumulative Number of HF Hospitalizations Days from Implant Abraham et al., Lancet 2011

  24. Secondary Efficacy Results

  25. CHAMPION: Putting It Altogether Pulmonary Artery Pressure Medication Changes On Basis of Pulmonary Artery Pressure P<0.0001 Pulmonary Artery Pressure Reduction P=0.008 Heart Failure Related Hospitalization Reduction P<0.0001 Quality of Life Improvement P=0.024 P values for Treatment Vs Control Group

  26. Implantable Sensor Lead (ISL) Lead Sensor Module Distal Anchor Proximal Anchor Sensor Diaphragm ~ 3 mm Implantable Communications Module (ICM) • Measures • LAP • IEGM • Core Temp Implantable LA Pressure Monitor

  27. HandheldPatient Advisor Module (s) carvedilol(25mg),1 tab(s) lisinopril(20mg), 1 tab*(d) furosemide(40mg),1 tab PAM • Powers implant by RF • Atmospheric reference • Stores telemetry • Alerts patient to monitor • DynamicRX™ • Meds, activity, MD contact

  28. Physician-Directed, Patient-Self Management LAP ≥28 …Very High… furosemide 80mg, call MDLAP 19-27 …High………. 40mg LAP 10-18 …Optimal…… 20mg LAP 6-9 … Low…………10mg LAP ≤ 5 …Very Low…. hold, increase fluid intake Optimal LAP makes it easier to up-titrate β-Blockers and ACE-I/ARBs Direct USB (in-clinic) RF Telemetry Remote(patient’s home) PAM Application SoftwareTrends, Waveforms, PrescriptionsPC or Web Based

  29. HOMEOSTASIS Trial ResultsReduction in Heart Failure Hospitalizations LAPTOP-HF, an adequately powered randomized controlled trial to assess clinical safety and effectiveness of this approach, is underway

  30. New Approach to the Non-Invasive Assessment of Lung Water • Proprietary RF monitoring and imaging technology • As fluid replaces air, there is an increase in the dielectric coefficient • Measurement is localized (lung-specific) as opposed to other modalities (e.g., bio-impedance) • Enables non-invasive and continuous monitoring of lung fluid concentration

  31. Superior Lobes ReDS Correlation with CT and Pressure(Pre-Clinical Data) Inferior (Dependent) Lobes Interclass Correlation = 0.95 Start of volume loading Diuretics CT + ReDS LVEDP, PAP Fluid concentration and pressures correlate during volume overload; a lag is observed during diuresis

  32. Left Ventricular Partitioning: Rationale Decrease LVEDV Decrease LVESV Reshape ventricle Decrease LV radius Reduce LV wall stress Increase contractility Prevent further remodeling/ reverse remodeling

  33. Percutaneous Ventricular Partitioning Device:System Components 75mm & 85mm diameter Deliver via 14/16 French Catheter Nitinol struts ePTFE membrane Radiopaque Pebax polymer foot Cardiokinetix, Inc., Menlo Park, California, USA

  34. Efficacy Results:LVESV, Paired data, mean ± SEM PARACHUTE All 1yr, n=28 p<0.001 200 p<0.001 196.1 160.9 150 155.3 LVESV (ml) 100 50 0 Baseline 12 months 6 months Abraham et al., HFSA 2010 LBCT Presentation

  35. Cardiac Support Devices • Primary goal is to reduces LV radius and transmural pressure, so that diastolic wall stress will fall • Other properties (e.g., elasticity) of such devices may provide ancillary mechanisms of benefit • First generation devices (e.g. CorCap™) required a major surgical procedure (i.e., sternotomy) • Newer devices (e.g., HeartNet™)can be placed via a minimally invasive approach and has unique elastic properties

  36. Minimally Invasive Approach to Ventricular Elastic Support Therapy • Super elastic compliant nitinol structure • Defibrillation, pacing compatible • Delivered with special delivery system through minithoracotomy • Self anchoring, self tensioning • Pre sized based on echo measurements

  37. Paracor HeartNet™ Compliance The elastic compliance allows the device to stretch and return to its original position

  38. PEERLESS-HF CRT Subset Data P=0.036 HR=2.2

  39. PEERLESS-HF CRT Subset Data P=0.06 HR=2.0

  40. reduce workload Extra-Aortic Counterpulsation Heart Fills - Cuff Inflates Heart Ejects - Cuff Deflates to body to heart Increased Blood Flow: + 60% coronary flow; + 30% cardiac output; Reduced Heart Workload: - 30% pulmon. Pressure; -33% LV wall stress

  41. C-Pulse for Moderate Heart Failure Patients Extra-aortic Cuff ECG Sense Lead Interface Lead Battery Pack Driver

  42. Ventricular Assist Devices • AHA estimates that 250,000 patients could benefit from long-term circulatory support • Potential Opportunities • Bridge to Transplant • est. 7,000 patients annually • Permanent Support or “Destination Therapy” • est. 40,000 patients annually • Bridge to Recovery • est. > 200,000 patients annually

  43. LVADs as Destination Therapy in End-Stage Heart Failure 100 80 60 40 20 0 Survival (%) LV Assist Device Medical Therapy 0 6 12 18 24 30 Months No. at Risk LV Assist Device 68 38 22 11 5 1 Medical Therapy 61 27 11 4 3 0 Rose et al., NEJM 2001

  44. LVADs as Destination Therapy in End-Stage Heart Failure 100 80 60 40 20 0 Survival (%) LV Assist Device Medical Therapy 0 6 12 18 24 30 Months No. at Risk LV Assist Device 68 38 22 11 5 1 Medical Therapy 61 27 11 4 3 0 Rose et al., NEJM 2001

  45. Ventricular Assist Devices • Generation II Devices (axial flow pumps) Characteristics: • small, simple designs • high rpm • easy insertion/removal (minimally invasive techniques) • durability risk/bearing Use (targeted): • temporary support • bridge to transplant • bridge to recovery • limited “permanent” use

  46. Heartmate II Axial Flow LVAD

  47. Ventricular Assist Devices • Generation III Devices (magnetic bearings) Characteristics: • high reliability • fewer mechanical parts • complex engineering • closed loop systems (?) Use (targeted): • temporary support • bridge to transplant • bridge to recovery • “permanent” use

  48. HeartWare Ventricular Assist System • Small implantable centrifugal pump • Designed to be implanted in the pericardial space • ?High rate of thrombotic complications

  49. Micro-pumps: Short-Term Use Impela 2.5 Percutaneous Heart Pump Delivers 2.5 L/min of flow Unloads the ventricle Designed for Ease of Use (Cath Lab) 9 Fr Catheter 12 Fr micro-axial pump

  50. Micro-pumps: Short-Term Use Impela 5.0 Requires arterial cutdown Delivers 5.0 L/min of flow Unloads the ventricle Surgical insertion 9 Fr Catheter 21 Fr micro-axial pump

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