| Eligibility |
Inclusion Criteria:
- 1. Ischemic or non-ischemic cardiomyopathy and documented heart failure for at least 6
months (diagnosis of HF = 6 months), regardless of ejection fraction.
2. NYHA Class II heart failure (HF) subjects, documented at Baseline Visit regardless of
ejection fraction, meeting both inclusion criteria in subsections (2a) and (2b) or NYHA
Class III heart failure (HF) subjects, documented at Baseline Visit regardless of ejection
fraction, meeting at least one inclusion criteria in subsections (2a) and (2b).
1. Have a minimum of one (1) HF hospitalization or equivalent (HF Emergency Department
Visit or HF Urgent Clinic Visit) within the last 12 months associated with
signs/symptoms of congestion requiring treatment with intravenous (IV) diuretic. If
Cardiac Resynchronization Therapy (CRT) device previously implanted, the HF
hospitalization or equivalent must be = 30 days after CRT implantation.
2. Have a corrected* elevated outpatient Brain Natriuretic Peptide (BNP) level of at
least 300 pg/ml or an N-terminal pro-BNP (NT-proBNP) level of at least 1,500 pg/ml,
according to local measurement, within 90-days of the Baseline Visit.
*Thresholds for NT-proBNP will be corrected for body mass index (BMI) using a 4%
reduction per BMI unit over 20 kg/m2. If subject is on ARNI, NT-proBNP should be used
exclusively.
3. Receiving maximally-tolerated medical therapy for heart failure as indicated per
ACC/AHA or ESC Heart Failure Guidelines (guideline-directed medical therapy or GDMT),
in the absence of contraindications and lack of availability. GDMT refers to those
guideline-directed medical therapies having a Class I indication for use.
- For patient with heart failure and a reduced ejection fraction (HFrEF), GDMT
includes a diuretic as needed for volume control, angiotensin-converting enzyme
(ACE) inhibitor or angiotensin receptor blocker (ARB) or angiotensin receptor
neprilysin inhibitor (ARNI), beta-blocker (BB), mineralocorticoid receptor
antagonist (MRA), and SGLT2 inhibitor for at least 3 months prior to the Baseline
visit. Drug doses, with the exception of diuretics, should be stable for at least
1 month, where stability is defined as no more than a 100% increase or 50%
decrease in dose.
- For patient with heart failure and a preserved ejection fraction (HFpEF), GDMT
includes a diuretic as needed for volume control and treatment of associated
conditions (e.g., hypertension, atrial fibrillation) for at least 3 months prior
to the Baseline visit. Drug doses, with the exception of diuretics, should be
stable for at least 1 month, where stability is defined as no more than a 100%
increase or 50% decrease in dose.
- Patients should also receive Class I recommended cardiac rhythm management device
therapy. Specifically: if indicated by class I guidelines, cardiac
resynchronization therapy (CRT), implanted cardioverter-defibrillator (ICD), or a
pacemaker should be implanted at least 3 months prior to Baseline Visit. These
criteria may be waived if a patient is clinically contraindicated for these
therapies or refuses them and must be attested to by the investigator.
- GDMT may change over time; the most current versions of the ACC/AHA or ESC Heart
Failure Guidelines will supersede the above guidelines.
4. Provide informed consent for study participation and be willing and able to
comply with the required tests, treatment instructions, and follow-up visits.
Exclusion Criteria:
- 1. Age less than 22 (<22) or greater than 88 (>88) years old. 2. Subjects who are
NYHA class IV and ACC/AHA stage D. 3. Subjects with evidence/history of a major
cardiovascular or neurovascular event, such as an intra-cardiac thrombus or
history of stroke, transient ischemic attack, systemic or pulmonary
thromboembolism, deep vein thrombosis (DVT), within the last 6 months of Baseline
Visit.
4. Subjects with a resting systolic blood pressure <90 or >180 mmHg. 5. Left
ventricular end-diastolic diameter (LVEDD) > 8cm. 6. Have an atrial septal defect
or patent foramen ovale with more than trace shunting on color Doppler or
intravenous bubble study or surgical or interventional correction of congenital
heart disease involving atrial septum, including placement of a PFO or ASD
closure device, and have a hypermobile septum or a septal aneurysm.
7. Subjects with untreated severe valve lesions, which are indicated for surgical
or percutaneous intervention, active valvular vegetations, atrial myxoma,
hypertrophic cardiomyopathy with significant resting or provoked subaortic
gradient, acute myocarditis, tamponade, or large pericardial effusion,
constrictive pericarditis, infiltrative cardiomyopathy (including cardiac
sarcoidosis, amyloidosis, and hemochromatosis), or congenital heart disease, as a
cause of HF.
8. Uncontrolled tachyarrhythmia or bradycardia (heart rate <45). 9. Intractable
HF with resting symptoms despite maximal medical therapy (ACC/AHA HF Stage D),
including subjects receiving continuous or intermittent outpatient IV vasoactive
medications (e.g., IV inotropes, IV vasodilators), subjects treated with a
ventricular assist device (VAD).
10. Intolerant to ACE-I, ARB, or ARNI and beta-blocker medical therapy for
subjects classified as HFrEF (EF =40%).
11. The presence of an acute coronary syndrome (ACS), percutaneous coronary
intervention (PCI), rhythm management system revision, lead extraction, or
cardiac or other major surgery within the preceding 90 days.
12. Subjects not eligible for emergency open-heart, thoracic or vascular surgery.
13. Women of childbearing age. 14. Subjects with a life expectancy that is
shorter than 12 months, or those who have received a cardiac transplant or are
listed for cardiac transplantation and likely to be transplanted within 12 months
of Baseline Visit.
15. Have coagulopathy or uninterruptible anticoagulation therapy or
contraindication for all the forms of antiplatelet/anticoagulant treatments
anticipated in the protocol.
16. Known history of life-threatening allergy to contrast dye that cannot be
properly pre-medicated.
17. Have an estimated Glomerular Filtration Rate (GFR) <20 ml/min/1.73 m2 by the
MDRD method or on chronic renal dialysis.
18. Hepatic impairment with at least one liver Function Test (transaminases,
total bilirubin, or alkaline phosphatase) = 3 times upper limit of normal.
19. Gastrointestinal bleeding in the last 6 months. 20. Have severe chronic
pulmonary disease requiring continuous home oxygen, chronic oral steroid therapy,
hospitalization for exacerbation during prior 6 months, or has severe obstructive
physiology on PFTs (FEV1/FVC <0.70 and FEV1 < 50% normal), if done.
21. Subjects who have an active infection requiring systemic antibiotics or an
elevated white blood count (above the local laboratory reference ranges).
22. Have a history of active drug addiction, active alcohol abuse, or psychiatric
hospital admission for psychosis within the prior 2 years.
23. Are currently participating in a clinical study or investigation. 24. Subject
otherwise not appropriate for study as determined by the investigator and
subjects who are unwilling to comply with the study protocol, or subjects with a
history of non-compliance. The reasons must be documented.
25. Subjects contraindicated for trans-septal puncture, TEE or ICE.
Intra Procedural Exclusion Criteria:
(Intra Procedural Exclusion Criteria will be determined immediately after intracardiac
echocardiography or transesophageal echocardiography determination of left atrial
anatomy and just before transseptal puncture) 26. Anatomical anomaly on TEE or ICE
that precludes implantation of the V-LAPIM across the interatrial septum (Fossa
Ovalis) including: Septal thickness at fossa > 5 mm, FO Dimension <16mm, ASD or PFO
with more than a trace amount of shunting, intra-cardiac thrombus felt to be acute and
not present on prior exams and abnormal septum, e.g., a hypermobile septum or a septal
aneurysm.
27. Inadequate vascular access for implantation of V-LAPIM or are unable to tolerate a
right heart catheterization (RHC).
28. Severe pulmonary hypertension at index procedure above 70 mmHg or PVR at index
procedure above 4.0 Woods Units (mmHg L-1 min-1), while these cannot be lowered with
vasodilators.
29. Resting systolic Blood Pressure <90 or >180 mmHg, not corrected with IV fluid
administration or vasodilators.
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