Clinical Trials

Primary Inclusion Criteria:

• Subject has severe (Grade III or greater per the ASE criteria, which includes severitygrades of 3+ and 4+) primary MR (mixed etiology is acceptable provided theprincipal mechanism of action is a degenerative mitral valve) as assessed bythe ECL.

• Subject is at least 75 years of age

• Completion of a Cytokinetics study investigating CK-3773274. If unable to complete due to circumstances not related to compliance or safety, Medical Monitor may review and determine eligibility.
• LVEF ≥ 55%

• Ejection Fraction >=45%
• In the hospital setting >24 hours for the management of acute decompensated heart failure (ADHF), or diagnosed with ADHF after being hospitalized for another reason

• Failing aortic bioprosthetic valve demonstrating ≥ moderate stenosis and/or ≥ moderate insufficiency
• Bioprosthetic valve size suitable for SAPIEN X4 THV based on computed tomography angiography (CTA) analysis
• NYHA functional class ≥ II

• Chronic symptomatic heart failure (HF)
• Ongoing stable GDMT HF management and management of comorbidities according to the 2022 ACC/AHA Guidelines for the Management of Heart Failure.

• A LVEF ≤ 50% within 6 months prior to enrollment
• Resting QRS duration ≥ 130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR
• Anticipated right ventricular pacing > 40% OR
• Device in place with right ventricular pacing > 40%; AND

• Documented history of symptomatic or asymptomatic paroxysmal or persistent AF
• CHA2DS2-VASC score of 1-4 without prior stroke or TIA
• Participant is on a DOAC at time of screening

Patient will undergo treatment with a Thoraflex Hybrid device

• PE symptom(s) duration ≤ 14 days from index procedure
• PE diagnosis ≤ 48 hours prior to index procedure
• CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery based on Investigator determination)
• CTA evidence of dilated RV with an RV/LV ratio of ≥ 0.9 at baseline based on Investigator determination
• Systolic blood pressure ≥ 90 mmHg without need for vasopressors (initial SBP may be ≥ 80 mmHg if the pressure recovers to ≥ 90 mmHg with intravenous fluids prior to index procedure)
• Stable heart rate < 130 BPM prior to index procedure

• Ascending Aortic pathologies warranting surgical repair
• Anatomic compatibility with the ASG device based on Gore Imaging Sciences review
• Must be considered high-risk for open surgical repair

Atrial fibrillation or flutter, paroxysmal or sustained not due to a reversible cause, and eligible to receive anticoagulation therapy

Listed for heart transplantation

• Chronic symptomatic heart failure (HF) due to non-valvular and noncongenital left heart disease (LHD)
• on stable medically optimized guideline-directed medical therapy (GDMT) for HFpEF/HFmrEF, for >30 days

Ambulatory with an age of 22-85 years at time of enrollment

Heart Failure with EF ≥ 40% (by TTE within last 3 months)

NYHA Class II or III

• NYHA Functional Classification II or III,
• Elevated NT-proBNP OR BNP with adjusted clinical thresholds (only ONE needed)
• Presence of structural or functional cardiac disease confirmed by echocardiographic evidence of at least one of the following
• (1) Increased LV filling pressures OR
• (2) Left atrial enlargement OR
• (3) LV hypertrophy
• LVEF ≥ 55%
• Established diagnosis of HFpEF consistent with local heart failure guidelines

• Patient with HF who signed the informed consent forms accepting his/her data collection and tele transmission
• Patient Presenting “acute heart failure event"
• Patient with blood test data ([B-type natriuretic peptide (BNP) or N-Terminal pro B type natriuretic peptide (NT-proBNP) at the acute HF event
• Patient with HF class III and IV according to the New York Heart Association functional classification

• NYHA Class II or III or ambulatory NYHA class IV symptoms
• A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics verified by right heart catheterization
• A qualifying Baseline RHC performed within 120 days of Day 1

Diagnosis of ATTR-CM

Medical history of HF

Treatment for HF/ATTR-CM is optimized and symptoms are clinically stable

• Persistent or permanent AF - OR- Paroxysmal AF in participants with a history of ischemic stroke or systemic embolism
• Increased risk of stroke, defined as a CHA2DS2-VASc score of ≥ 4
• Treatment with OAC for at least 90 days prior to enrollment, AND no documented plan to permanently discontinue treatment with OAC for the expected duration of the trial

• A screening LVEF between 40% and 65% in the absence of hemodynamically significant and/or severe valvular disease on 2D-TTE, with at least one other documented LVEF measurement between 40% and 65% and within 52 weeks prior to screening as confirmed by echocardiography, radionuclide ventriculogram, cardiac CT, or CMR, AND
• Elevated level of NT-proBNP (≥ 600 pg/mL)
• Documented evidence of paroxysmal (on ≥ 2 occasions ≥ 1 week apart), persistent or permanent atrial fibrillation/flutter by electrocardiogram, Holter, implantable device, or telemetry based event monitoring within the last 5 years

• NYHA functional class II or III
• A diagnosis of HCM
• For oHCM, LVOT peak gradient ≥ 30 mm Hg at rest OR during a Valsalva maneuver at Screening visit
• For nHCM, LVOT peak gradient < 30 mm Hg at rest AND during a Valsalva maneuver at Screening visit
• Screening LVEF ≥ 50%. For patients on a cardiac myosin inhibitor, the Screening LVEF must be ≥ 55%

• Stable New York Heart Association (NYHA) Class II or III HF diagnosis, evident at least 6 months prior to enrolment as confirmed by medical history
• Documented prior objective evidence of heart failure
• Meets 1 or more of the following criteria at the initial Screening measurement:
• A high sensitivity cardiac troponin I > 34 pg/mL
• For participants with body mass index (BMI) <30 kg/m2, a Screening NT-proBNP >300 pg/mL
• For participants with BMI≥30.0 kg/m2, a Screening NT-proBNP >240 pg/mL
• Body mass index (BMI) ≥18 kg/m2 and ≤45 kg/m2
• Screening ejection fraction ≥50%

• Multivessel or left main CAD is present for which revascularization is intended and for which there is equipoise between CABG and PCI according to local Heart Team assessment

• Symptomatic coronary artery disease (CAD)
• Must have attempted treatment with the maximally tolerated dose of at least three of the four (preferably all four) approved classes of anti-anginal agents: long-acting nitrates, calcium channel blockers (either a dihydropyridine or a non-dihydropyridine), beta blockers, and ranolazine
• Subject has either no treatment options for revascularization by coronary artery bypass grafting or by percutaneous coronary intervention, or is otherwise unsuitable or high risk for revascularization as determined by the local heart team, and confirmed by a Central Screening Eligibility Committee

• A history of recurrent pericarditis* with stable disease and currently being treated with an IL-1 blocker, scheduled to be discontinued
• Pericarditis pain ≤ 2 on the 11-point Numerical Rating Scale (NRS) for at least the prior 7 days
• C-Reactive Protein (CRP**) < 1.0 mg/dL within the 7 days of screening prior to Day 1 (Visit 1)

• Previously had an index (first) episode of pericarditis which, in the judgement of the Investigator based on the available data, met the criteria for an acute pericarditis event
• In the judgement of the Investigator, based upon the available diagnostic information, has an ongoing symptomatic episode of pericarditis, or may have an episode of recurrent pericarditis within the screening period
• CRP assessment by local laboratory assessment prior to first dose of study treatment on Day 1, either:
• a. CRP > 10 mg/L, or b. CRP ≤ 10 mg/L
• Pericarditis pain score ≥ 4 based on the 11-point NRS on Day 1

• Patient has a history of heart failure
• Patient has a left ventricular ejection fraction measured within 6 months of study enrollment recorded in the medical record
• Patient is scheduled to undergo a right heart catheterization (RHC) procedure per standard of care, which will include direct PCWP and PAP measurement
• Patient is willing to wear the CardioTag device during their RHC procedure

• Is suspected of having cardiac amyloidosis and is undergoing or will undergo a diagnostic evaluation for cardiac amyloidosis (e.g., echocardiography, CMR, bone avid tracer cardiac SPECT, extracardiac or endomyocardial biopsy, etc.). Participants can be enrolled before or during their diagnostic evaluation for cardiac amyloidosis.
• Able to undergo PET/CT imaging as part of the study, including ability to lie supine for approximately 1 hour.