CORolla™ TAA for Heart Failure and Preserved Ejection Fraction and Diastolic Dysfunction

Study Overview
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Brief Summary
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The study purpose is to evaluate the safety and feasibility of the CORolla™ TAA in two treatment groups, CORolla™ Stand-alone group and  AVR & CORolla™ Add on group.

Conditions
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Diastolic Heart Failure NYHA Class III-IV, Diastolic Dysfunction Secondary to Aortic Stenosis

Intervention / Treatment
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* Device: CORolla™ TAA device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical criteria Adult (age > 18 years) Diagnosis of heart failure with preserved systolic function according with ESC 2008 Guidelines (ejection fraction ≥ 50%) NYHA F. Class III or IV symptoms with history of previous heart failure hospitalization in the last year Able to sign informed consent and return for follow-up visits. No contraindication for anticoagualation and antiplatelet treatment. Cardiac medications unchanged for greater than 4 weeks (not including diuretics) Pulmonary Wedge pressure > 15 mmHg documented by right heart catheterization at enrollment. Echocardiographic criteria Preserved regional wall motion (no wall motion abnormalities). Left ventricular ejection fraction ≥ 50% LV end-diastolic volume index (LVEDVI) <97 ml/m2. Left Atrial Volume Index: (LAVi >29 ml/m2). E/E' ratio ( mean of septal and lateral ) ≥12 (applicable only to patients with sinus rhythm) No intra-cardiac thrombus. Minimal endocardial height from Apex to Mitral Annulus ≥ 70mm. Exclusion Criteria: Cardiovascular disease Uncontrolled HTN defined as > 140/90 mmHg, or >160/90 mmHg for patients on 3-drug therapy Current or anticipated need for ICD, currently implanted with a cardiac resynchronization device (CRT), left ventricular assist device (LVAD). Within the past 3 months - Acute myocardial infarction (AMI), cerebral vascular accident (CVA), Transient Ischemic Attack (TIA) , Percutaneous coronary intervention (PCI or transmyocardial laser revascularization (TMR or PMR) Valvular disease (unless add - on to aortic valve replacement due to aortic stenosis) Hypertrophic cardiomiopathy Pericardial disease Cor pulmonale or other cause of isolated right heart failure. Non reversible pulmonary hypertension. Right ventricle failure or right ventricular myocardial infarction. Infiltrative heart disease Non-cardiovascular disease Non-cardiovascular condition limiting ability to assess the 6-minute hall walk test Prior surgery, radiation, or thoracic surgery limiting the ability to place the device Body mass index of greater than 40 Uncontrolled hyperglycemic status as addressed by HbA1c >8.5% Asthma COPD (e.g. FEV1 <1.5 liter), or severe restrictive lung disease Severe chronic renal failure indicated by MDRD GFR <30 mL/min/1.73 m2 Liver impairment addressed by bilirubin > 2 mg/dl and or pseudo- colinesterasis plasma concentration < 1500 IU and/or abnormal coagulative profile Severe anemia addressed by Hb concentration <10 gr/l. Solid organ or hematologic transplant. Previous Trans Apical procedures/implantation Miscellaneous conditions Unwilling to fulfill the protocol medication compliance, testing, and follow-up requirements Co-morbid condition that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements Pregnancy at the time of enrollment. (Women of child bearing potential must have a negative serum pregnancy test within two weeks prior to enrollment, or be using hormonal contraceptives or intrauterine devices) Enrolled in another investigational study A history of alcohol abuse, drug addiction, or other psychosocial condition that would preclude successful participation, or clear judgment and informed consent in the opinion of the Principal Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CORolla™ TAA Stand Alone<br>Single arm study design including with patients with isolated HFpEF, in NYHA f. Cl. III-IV. These patients will receive the CORolla™ TAA device. For assessments of results, intra-patient comparisons of pre-procedure and follow-up data will be performed; | Device: CORolla™ TAA device<br> <br> |
| Experimental: AVR and CORolla™ TAA Add On group<br>patients who require aortic valve replacement (AVR) due to aortic stenosis and have diastolic dysfunction will receive the CORolla™ TAA device. | Device: CORolla™ TAA device<br> <br> |
| No Intervention: AVR and CORolla ADD On - Control<br>patients who require only the aortic valve replacement (AVR) due to aortic stenosis and have diastolic dysfunction. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovasculare related SAEs | Investigational device safety with the intended study population with respect to 12 months follow up will be demonstrated using the following: Cardiovascular mortality and morbidity reports at 30 days post surgery. Serious adverse events: death, arrhythmia, CVA, AMI, bleeding and valve injury at 12 months post-surgery. | 12 month post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility | Change in Quality of Life (QoL): Minnesota Living with Heart Failure. | up to 36 month post surgery | 
| Feasibility | Change in NYHA f. class | up to 36 month post surgery | 
| Feasibility | Change in exercise capacity as measured by the Six-Minute Walk test | up to 36 month post surgery | 
| Feasibility | Composite rate of HF death and re-hospitalization at 6 months and 1 year. | Up to 36 month post surgery | 
| Feasibility | Impact of CORolla™ TAA therapy on markers of diastolic dysfunction assessed by conventional echocardiography imaging (e.g LAVI index etc)and novel approach including Tissue Doppler Imaging (TDI) | up to 36 month post surgery | 
| Feasibility | Change of Wedge pressure - for safety assessment and impact of CORolla™ TAA therapy on this marker of diastolic dysfunction | up to 36 month post surgery | 
| Feasibility | Changes in cardiac medical therapy including daily diuretic dose | up to 36 month post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure with Preserved Ejection Fraction (HFpEF), Diastolic Heart Failure (DHF), Diastolic Dysfunction (DD)