|Principal Investigator: John Ryan|
|Keywords: IASD® System II , Randomization , Reduce , Heart Failure , LVEF >40% , HFpEF||Department: Cardiovascular Medicine|
|IRB Number: 00103567|
|Specialty: Cardiology, Cardiology, Cardiology, Cardiology|
|Sub Specialties: Interventional Cardiology, General Cardiology, Heart Failure|
|Recruitment Status: Completed|
The primary objective of this randomized controlled clinical trial is to evaluate the clinical efficacy and safety of the IASD System II in symptomatic heart failure patients with an LV ejection fraction ≥40%, and elevated left sided filling pressures despite standard Guideline Directed Medical Therapy (GDMT)
5.1.1 Inclusion Criteria
Candidates for this study must meet all of the following inclusion criteria:
1. Chronic symptomatic heart failure (HF) documented by the following:
a. Symptoms of HF requiring current treatment with diuretics for ≥ 30 days AND
b. New York Heart Association (NYHA) class II if a prior history of > OR NYHA class II; NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening visit; or signs (any rales post cough, chest x-ray demonstrating pulmonary congestion,) within past 12 months; AND
c. ≥ 1 HF hospital admission (with HF as the primary, or secondary diagnosis); or treatment with intravenous (IV), or the need for intensification of oral diuresis for HF in a healthcare facility (emergency department/acute care facility), within the 12 months prior to study entry; OR an NT-pro BNP value > 150 pg./ml in normal sinus rhythm, > 450 pg./ml in atrial fibrillation, or a BNP value > 50 pg./ml in normal sinus rhythm, > 150 pg./ml in atrial fibrillation within the past 6 months
2. Ongoing stable GDMT HF management and management of potential comorbidities according to the 2017 ACCF/AHA Guidelines for the management of Heart Failure with no significant changes (>100% increase or 50% decrease), excluding diuretic dose changes for a minimum of 4 weeks prior to enrollment which is expected to be maintained for 6 months. Stable management includes a minimum period of 4 weeks post hospitalization for any cause, including treatment with IV diuretics.
3. Age ≥ 40 years old
4. Site determined echocardiographic LV ejection fraction ≥ 40% within the past 6 months, without documented ejection fraction <30% in the 5 years prior to study entry
5. Site determined elevated PCWP with a gradient compared to right atrial pressure (RAP) documented by
a. End-expiratory PCWP during supine ergometer exercise ≥ 25mm Hg, and greater than RAP by ≥ 5 mm Hg.
6. Site determined echocardiographic evidence of diastolic dysfunction documented by one or more of the following:
a. LA diameter > 4 cm; or
b. Diastolic LA volume > 50, LA volume index > 28 ml/m2 or
c. Lateral e’ < 10 cm/s; or
d. Septal e’ < 8 cm/s; or
e. Lateral E/e’ > 10; or
f. Septal E/e’ > 15
7. Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the IRB or EC
8. Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
9. Trans-septal catheterization and femoral vein access is determined to be feasible by site interventional cardiology investigator.
5.1.2 Exclusion Criteria
Candidates for this study will be excluded if any of the following conditions are present:
1. MI and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization; AVR (surgical AVR or TAVR) within the past 12 months
2. Cardiac resynchronization therapy initiated within the past 6 months
3. Advanced heart failure defined as one or more of the below:
a. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF;
b. Cardiac Index < 2.0 L/min/m2
c. Inotropic infusion (continuous or intermittent) for EF < 40% within the past 6 months
d. Patient is on the cardiac transplant waiting list
4. Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk test > 600m
5. The patient has verified that the ability to walk 6 minutes is limited primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or lifestyle and not by shortness of breath and/or fatigue and/or chest pain.
6. Unwilling or unable (per PhysIQ protocol) to wear tele-monitoring patch.
7. Known clinically significant un-revascularized coronary artery disease, defined as: epicardial coronary artery stenosis associated with angina or other evidence of coronary ischemia.
8. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
9. Known clinically significant untreated carotid artery stenosis likely to require intervention
10. Presence of hemodynamically significant valve disease assessed by the site cardiologist and defined as:
a. Mitral valve disease defined as grade ≥ 3+ MR or > mild MS; OR
b. Tricuspid valve regurgitation defined as grade ≥ 2+ TR; OR
c. Aortic valve disease defined as ≥ 2+ AR or > moderate AS
11. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis or other infiltrative cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
12. Subject is contraindicated to receive either dual antiplatelet therapy, or an oral anticoagulant; or has a documented coagulopathy
13. Atrial fibrillation with resting HR > 100 BPM
14. Resting arterial oxygen saturation < 95% on room air
15. Significant hepatic impairment defined as 3X upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
16. Right ventricular dysfunction, assessed by the site cardiologist and defined as
a. More than mild RV dysfunction as estimated by TTE; OR
b. TAPSE < 1.4 cm; OR
c. RV size ≥ LV size as estimated by TTE; OR
d. Ultrasound or clinical evidence of congestive hepatopathy; OR
e. Evidence of RV dysfunction defined by TTE as an RV fractional area change < 35%;
17. Resting RAP > 14 mmHg
18. Evidence of significant pulmonary hypertension defined as PVR > 3.5 Woods units at rest or at peak exercise.
19. Chronic pulmonary disease requiring continuous home oxygen, OR significant chronic pulmonary disease defined as FEV1 < 1L
20. Hemoglobin <10 g/dl
21. Currently participating in an investigational drug or device study that would interfere with the conduct or results of this study. Note: trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational
22. Life expectancy less than 12 months for non-cardiovascular reasons
23. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.
24. Known or suspected allergy to nickel
25. Women of child bearing potential
26. Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by CKD-Epi equation
27. Systolic blood pressure >170 mm Hg at screening
28. Subjects with existing or surgically closed (with a patch) atrial septal defects. Subjects with a patent foramen ovale (PFO), who meet PCWP criteria despite the PFO, are not excluded.
29. Subjects on significant immunosuppressive treatment or on systemic steroid treatment (>10 mg prednisone/day).
30. Severe obstructive sleep apnea not treated with CPAP or other measures
31. Severe depression and/or anxiety
32. In the opinion of the investigator, the subject is not an appropriate candidate for the study
33. BMI >45. BMI 40-45 is also excluded unless in the opinion of the investigator, vascular access can be obtained safely.