I have nothing to disclose wish I did but I don t

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1 Disclosure I have nothing to disclose wish I did but I don t Minor Disclosure Emerging Research in Heart Failure Jan Shanahan ANP-BC Heart Failure Clinic GRAPEVINE-HF Investigators GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection Fraction Heart Failure Principle Investigator Scott Hummel MD, University of Michigan Co-Investigators Marlo Leonen MD, Michigan Heart Jan Shanahan NP, Michigan Heart Research Coordinator Nora Marchelletta RN, Michigan Heart

2 Background Study Purpose Over half of patients hospitalized for HF have diastolic dysfunction (HF-PSF) Many people with HF-PSF have longstanding HTN but little is known about the specific factors that precipitate HF Animal models suggest salt sensitive HTN and oxidative stress play a role Human and animal studies suggest that grape seed has potential cardio protective effects by increasing plasma antioxidant capacity The focus of this research is to understand how dietary supplements with grape seed extract changes levels of hormones and chemicals that damage the heart and blood vessels in patients with a history of high blood pressure and diastolic heart failure Inclusion Criteria Exclusion Criteria Age > 50 S&S of HF Diastolic dysfunction on echo Hx of HTN (even if well controlled) Willing to take study drug/placebo BID for 12 weeks On daily high dose antioxidants NYHA Class IV HF hospitalization in last month SBP >180 and/or DBP >100 HGB A1c >9% GFR <30, severe hepatic disease Hgb <9 Severe pulmonary disease Severe mitral or aortic stenosis or insufficiency Restrictive cardiomyopathy as etiology of HF-PSF Mi or USA within 3 months Uncontrolled arrhythmia Psychiatric disorder On both anti-platelet and anti-coagulation therapy

3 Study Design LAPTOP-HF Randomized, placebo controlled, doubleblinded, crossover design 6 weeks of GSE, 2 week wash-out period, and 6 weeks of placebo Baseline and end of study assessment of neurohormonal markers, collagen turnover, arterial stiffness, endothelial function, systolic and diastolic function, maximal exercise capacity, oxygen consumption and HF related QOL will be done 17 patients enrolled at UM with 3 from St. Joes Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy Study Investigators Background Study Sponsor St. Jude Medical Principle Investigator Tim Shinn MD, Michigan Heart Co-Investigator Marlo Leonen MD, Michigan Heart Jan Shanahan NP, Michigan Heart Research Coordinator Cheryl Marentette RN, Michigan Heart Elevated pulmonary capillary wedge pressures (PCWP) is considered a surrogate for left-sided pressures PCWP predicts increased HF morbidity & mortality The SJM LAP System was developed as an implantable device to provide direct LAP measurements along with a feedback loop for medication adjustments

4 Implantable Sensor Lead (ISL) Implantable Communications Module (ICM) Stand-Alone ICM Distal Anchor Telemetry Coil Proximal Anchor Sensor Diaphragm Auricle/Promote LAP has an extra lead port for ISL (standard IS-1). The coil is incorporated in header and is electronically and mechanically isolated. Final Superior Placement Patient Advisor Module (PAM) All patients will receive a PAM that will: Store medications, symptoms, BP, and weight Provide a reminder to take medications a minimum of twice daily In the treatment group, the PAM communicates with the ICM and will: Measure and store LAP, core temperature, and IEGMs Deliver the clinician s prescription based on LAP result In the control group, the PAM will: Remind the patient to take medications as prescribed

5 Patient Management System Study Purpose Patient obtains LAP readings with PAM handheld prior to meds Patient uses DynamicRX guided therapy to self-titrate HF meds OBJECTIVE -Control LAP Excursions -Titrate HF Meds to Recommended Doses LAP data uploaded to Clinician s PC Software Clinician formulates DynamicRX guided therapy based on LAP data trends To demonstrate that long-term direct LA pressure monitoring combined with a system of provider-directed daily patient selfmanagement will improve hemodynamics and limit hospitalizations for acute decompensated heart failure in patients with advanced heart failure Inclusion Criteria Inclusion Criteria Ischemic or non-ischemic cardiomyopathy with either a history of reduced or preserved ejection fraction and heart failure for at least 6 months. NYHA Class III Receiving appropriate medical therapy for heart failure as per ACC/AHA guidelines for at least 3 months prior to randomization. On stable medications* maximized to the subject s tolerance of ACE or ARB and beta-blockers as determined by the study investigator for at least 30 days prior to randomization. *Stable is defined as no more than a 100% increase or 50% decrease in dose. These criteria may be waived if a subject is intolerant of ACE, ARB or betablockers, or these agents are not indicated under the Guidelines. Such intolerance or lack of indications must be documented. Have a minimum of 1 prior hospital admission within the last 12 months for acute exacerbation of HF requiring intravenous or invasive HF therapy. If CRT device previously implanted, the heart failure hospitalization must be 30 days after CRT implantation. Alternatively, if patients have not had a heart failure hospitalization within the prior 12 months, they must have an elevated BNP of 400pg/ml or an N-terminal pro-bnp (NT-pro BNP) level of at least 1,500pg/ml. Provide informed consent for study participation. Are able to schedule Therapy Initiation Visit, which includes device implantation if indicated within two weeks.

6 Exclusion Criteria Exclusion Criteria Intractable HF with resting symptoms despite maximal medical therapy (persistent NYHA Class IV or ACC/AHA HF Stage D). Resting systolic blood pressure < 80 or > 180 mmhg. Acute MI, ACS, PCI, new CRM device, revision, extraction or other major surgery within 40 days. Coexisting, untreated, hemodynamically severe stenotic valve lesions, vegetations, hypertrophic cardiomyopathy with significant resting or provoked sub aortic gradient, acute myocarditis, tamponade, or large pericardial effusion. ASD, PFO (with more than trace shunting on color Doppler or IV bubble study) or surgical correction of significant congenital heart disease involving atrial septum such as PFO or ASD closure device. Inadequate vascular access for device implantation. Stroke or Transient Ischemic Attack within 6 months. Unresolved LA or LV thrombus. Recent or persistent DVT, pulmonary or systemic thromboembolism. Coagulopathy or uninterruptible anticoagulation therapy or contraindication for all forms of antiplatelet/anticoagulant treatment anticipated in the protocol Estimated GFR that remains < 30 ml/min Liver Function Test > 3 times upper limit of normal Severe pulmonary disease producing frequent hospitalizations for respiratory distress and requiring continuous home oxygen Pulmonary hypertension with a pulmonary artery systolic pressure > 80 mmhg on screening echo Active infection requiring systemic antibiotics History of active drug addiction, active alcohol abuse, or psychiatric hospital admission for psychosis within the prior 2 yrs Currently in a clinical trial with an active treatment arm Life expectancy < 1 year, < 18 yrs old, pregnant Unable to demonstrate capability of using PAM No access to telephone line or power outlet for remote follow-up and charging of PAM Study Design EchoCRT Prospective, Multi-center Randomization 1:1 Treatment/Control Treatment group will have LAP sensor implanted, ongoing LAP readings utilizing the PAM, and LAP based medication dosing Control group will have no LAP sensor implant, but will receive the PAM for medication reminders Crossover will not be allowed during the trial Patients will be further stratified based on EF and indication for CRM device 730 patients / 75 US sites 6 patients enrolled at St. Joes

7 Investigators Background Study Sponsor - Biotronik Principle Investigator Steve Girard MD, Michigan Heart Co-Investigator Jan Shanahan NP, Michigan Heart Research Coordinator Nora Marchelletta RN, Michigan Heart CRT is a recognized beneficial therapy for patients with persistent NYHA Class III symptoms despite being on maximal medical therapy who have a QRS width >120 ms It is known that mechanical dyssynchrony can be demonstrated on echocardiogram in some individuals despite a narrow QRS on EKG Elements of Cardiac Dyssynchrony Study Purpose Atrio- ventricular Intra- ventricular Inter- ventricular To evaluate the effects of cardiac resynchronization therapy (CRT) on the mortality and morbidity of patients with heart failure due to left ventricular systolic dysfunction, already receiving current standard HF medication, with a narrow QRS width (<130 ms) and echocardiographic evidence of ventricular dyssyhnchrony Cazeau, et al. PACE 2003; 26[Pt. II]:

8 Inclusion Criteria Exclusion Criteria 18 years of age or older Give informed consent, understands the procedure and willing to complete all testing Indication for an ICD NYHA Class III-IV within last 3 months Resting QRS < 130 ms Stable and optimal HF medications for 1 month LVEF < or equal to 35% LVEDD > than or equal to 55 mm Evidence of ventricular dyssynchrony on echo Contraindication to ICD Pt. with PM or ICD with >10% ventricular pacing Women who are pregnant or lactating Bradycardia pacing indication Surgically corrected valvular disease CABG or PCI within the last 3 months Enzyme positive MI in last 3 months Planned CABG or PCI in next 3 months Irreversible brain damage Reversible NICM such as acute viral Permanent 2 or 3 degree heart block Chagas disease Exclusion Criteria Study Design Persistent or permanent AF within 1 month Currently on inotropic therapy Acute decompensated HF Contrast dye allergy, unable to undergo pre-treatment Expected heart transplant or LVAD in 6 months Life expectancy < 6 months Creatinine > 2.5 within last 4 weeks Liver failure (3X ULN) Participating in another clinical trial Will not be a resident in the area for the duration of the trial Randomized, prospective, parallel, doubleblinded, multi-center international trial Patients and the HF investigators are blinded 1258 patients randomized at 125 sites 1:1 randomization to CRT=On or CRT=OFF Endpoints include hospitalizations for worsening HF, change in NYHA Class, MLHF QOL, composite score of death & hospitalization, and change in QOL, all cause mortality, Six Minute Walk, BNP, and AF burden 47 patients enrolled at St. Joes

9 ROADMAP ROADMAP Risk Assessment and Comparative Effectiveness Of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients Famous LVAD Patients Even More Famous Patients with LVAD

10 Investigators Background Study Sponsor Thoratec Corporation Principle Investigator Marlo Leonen MD, Michigan Heart Co-Investigator Jan Shanahan NP, Michigan Heart Research Coordinator Nora Marchelletta RN, Michigan Heart Mechanical circulatory support (MCS) with the LVAD is an important therapeutic option for the patient with advanced heart failure Studies show that ambulatory HF patients with LVAD have better survival and reduced LOS compared to inotrope dependent patients The device is approved for both bridge to transplant (BTT) and destination therapy (DT) LVADs are typically implanted in inotropic dependent patients with only 20% in noninotropic dependent patients with NYHA Class IIIb-IV Study Purpose Inclusion Criteria The goal of this study is to assess differences in survival, quality of life, and functional status between LVAD supported patients and those who continue to receive optimal medical therapy and to use preoperative risk stratification to assess differences in severity of illness Age years NYHA Class IIIb-IV LVEF < or equal to 25% Not currently listed for heart transplant On optimal medical therapy 6MWT < 300 meters One hospitalization in last 12 months or at least 2 unscheduled ED or infusion clinic visits for HF in last 12 months

11 Exclusion Criteria Study Design Mechanical aortic or mitral valve Platelet ct < 100,000 Any inotrope within 30 days Inability to perform 6MWT Any other condition that would limit survival to < 2 years History of any organ transplant Presence of any systemic infection Unresolved stroke within 90 days Contraindication to anticoagulation/antiplatelet tx GFR < 25 or need for CRRT in last 3 months CRT or CRT-D within last 3 months Pregnancy Prospective, multi-center, nonrandomized controlled observational study 50 sites and 200 ambulatory NYHA Class IIIb/IV patients not dependent on inotropes who meet FDA criteria for MCS for DT Primary endpoint is composite of survival and functional improvement 1 year follow-up for primary endpoint with all patients followed for 2 years 1 patient in process of enrollment at St. Joes PARACHUTE IV Investigators Study Sponsor - Cardiokinetix Study of first-of-a-kind percutaneous catheter based structural heart solution to improve the lives of patients with ischemic heart failure Principle Investigator Art Szyniszewski MD, Michigan Heart Co-Investigator Marlo Leonen MD, Michigan Heart Jan Shanahan NP, Michigan Heart Research Coordinator Kristy Wippler RN, Michigan Heart

12 Background Background Parachute Device Echocardiographic Results

13 Study Purpose Inclusion Criteria The goal of this study is to demonstrate the safety and effectiveness of the Parachute implant in the treatment of patients with NYHA Class III or IV heart failure due to ischemic heart disease Age years BMI < or equal to 40 Symptomatic IHD (NYHA III or ambulatory IV) post MI in the LAD territory 60 days prior to enrollment Not hospitalized Appropriate medical therapy LVEF 15-35% Post LV MI structural heart dysfunction with LV wall motion abnormality by echo LV must have appropriate anatomy for implant Exclusion Criteria Study Design Untreated significant CAD requiring revascularization Cardiogenic shock within 72 hours PPM, ICD or CRT within 60 days Excessive WMA outside of the anterior-apical region CVA or TIA within 6 months ESRD on dialysis or creatinine > 2.5 OSA unless compliant with CPAP Hgb < 10 for female & <12 for male Contraindication to ASA, heparin, warfarin, or sensitivity to contrast which cannot be pre-medicated Prosthetic heart valve in mitral or aortic position Moderate valvular stenosis or regurgitation > 2+ Multi-center, 1:1 randomized, unblinded, prospective trial Will enroll in 2 phases, Phase I will be 50 patients with Phase II with patients clinical centers 6mon and annual 1-5 year follow-up Assessments include echo, NYHA Class, ECG, QOL survey and 6MHW test Endpoint is event driven (208 deaths or rehospitalizations) and all patients have had at least 12 months of follow-up 1 patient in process of enrollment at St. Joes

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