Clinical Trials

• No kidney disease (eGFR is greater than 45)
• Does not have severe claustrophobia

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

Primary Inclusion Criteria:

• Patients ≥ 18 years old
• Patients with paroxysmal or persistent AF undergoing routine pulmonary vein isolation (PVI)
• Patients undergoing a cardiac MRI prior to AF ablation

Primary Exclusion Criteria:

• Contraindication to MRI
• Abnormal renal function (eGFR < 60 mL/min/1.73 m2)

• 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%

• 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

• 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

• Presence of severe or greater tricuspid regurgitation as determined by the Echo Core Lab
• Patient is symptomatic despite medical therapy
• The local Site Heart Team determines the Patient is appropriate for transcatheter valve intervention

• 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

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

Diagnosis of ATTR-CM

Medical history of HF

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

• Recent use of an FDA-approved immune checkpoint inhibitor
• A diagnosis of myocarditis
• Hospitalized at the time of randomization
• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug

• Part 1: Cases will include subjects with severe AS according to ASE guidelines. Controls will include subjects with no significant AV disease, defined as a peak AV velocity <2 m/sec and no more than mild aortic regurgitation
• Part 2: Subjects with severe AS according to ASE guidelines who are scheduled for a transcatheter aortic valve replacement (TAVR) procedure
• Part 3: Subjects with mild, moderate, and severe AS according to ASE guidelines
• Part 4: Subjects with AS of any severity according to ASE guidelines, who are referred for exercise echocardiography

• 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%

• 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

• 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

• Subject with symptomatic severe or greater tricuspid regurgitation
• Subject is evaluated by Institutional Heart Team9 as being at increased operative risk
  • TR severity of at least 3 (severe) on a scale of 0 (none) to 5 (torrential), assessed by independent core lab and
  • Symptoms requiring use of diuretics

• Symptomatic according to New York Heart Association (NYHA) functional class (FC) II or highera
• Severe AR, as assessed by Imaging Core Laboratory
• High risk for surgery as judged by a multi-disciplinary heart team

• Patient is clinically indicated for a saline contrast TTE study with a suspected right-to-left shunt

• Has moderate CAVS (confirmed by the Imaging Core Laboratory)
• Has a left ventricular ejection fraction of 45% at the time of Screening as determined by the Imaging Core Laboratory
• Has an estimated glomerular filtration rate (eGFR) 30 mL/min/1.73 m2 as measured by the Chronic Kidney Disease Epidemiology Collaboration 2021 formula at the time of Screening

• Has a body mass index (BMI) ≤35 kg/m2
• Has adequate acoustic windows for echocardiography
• Has a clinical diagnosis of HCM consistent with current American College of Cardiology/American Heart Association and European Society of Cardiology Guideline definition with unexplained LVH in the absence of other cardiac or systemic disease which can produce the magnitude of hypertrophy observed
• Has had confirmation of nHCM by central review process based on screening rest and
• exercise stress echocardiography that meets criteria

• Moderate-severe or severe MR (grade 3+ to 4+); either degenerative MR (DMR) or functional (FMR)
• Symptomatic MR (i.e., NYHA Class ≥ II) despite optimal or maximally tolerated guideline-directed medical therapy (GDMT)
• Deemed to be at elevated risk for conventional mitral valve surgery by the heart team

• Clinical diagnosis of chronic heart failure for at least 3 months prior to screening visit (V1), with each of the following criteria:
  • New York Heart Association (NYHA) Class II-IV at V1
  • Left ventricular ejection fraction (LVEF) > 40% based on most recent assessment available in medical records
• Evidence of the following on screening echocardiogram performed during V2, based on analysis by central reader:
  • LVEF >40%
  • If LVEF ≥50%, with one or more structural heart abnormalities
• Evidence for elevated cardiac filling pressures within 12 months of screening (V1)

• Type 2 diabetes mellitus requiring pharmacologic therapy or with their most recent A1c > 6.5%, prediabetes
• Have a device (e.g., smartphone, tablet, computer) for communication with the central cardiologist-led team managing drug treatment for the CAD stage-based care group

• Have an established diagnosis of ATTR-CM (ATTRwt or ATTRv), with cardiac amyloid infiltration, increased LV wall thickness, and HF
• Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness ≥12 mm
• Chronic HF (NYHA I-IV)
• NT-proBNP concentration ≥1000 pg/mL at screening. Note: Participants with NT-proBNP levels between 1000 and 2000 pg/mL may be enrolled until a cap of 35% of the total study population is reached.
• Completed >50 meters on the 6MWT at screening

• The subject is a candidate for TAVR using the DurAVR® THV System, and a SAPIEN series THV system or an Evolut series THV System.
• The local Heart Team* agrees that the subject has an appropriate indication for, and will benefit from, TAVR due to native calcific valve severe aortic stenosis

• Has a body weight of at least 40 kg at Screening
• Has a history of pericarditis that in the opinion of the Investigator was consistent with the 2015 ESC Guidelines for the Diagnosis and Management of Pericardial Diseases
• Currently, has RP which is well controlled, i.e., including having CRP < 0.5 mg/dL within 14 days of Baseline and a pericarditis pain NRS score ≤ 3 at Baseline
• Has a documented history of CRP elevation (> 1 mg/dL) associated with at least one prior acute pericarditis episode, whether the incident event or any pericarditis recurrence

• Has a diagnosis of DCM due to probable disease-causing variants of MYH7, TTN, or other identified genetic DCM variants, or with familial DCM
• Has New York Heart Association (NYHA) Class II-IV at Screening with stable symptoms for ≥1 month
• Has chronic DCM, defined as not due to acute or possibly reversible conditions (e.g., hyper/hypothyroidism, infectious cause, tachyarrhythmia, iron overload), according to the Investigator

• Subject is eligible for percutaneous coronary intervention (PCI)
• Target lesion is a de novo lesion located in a native coronary artery and meets at least 1 of the 3 criteria

• Despite Optimal Medical Therapy (OMT) per the local Heart Team, patient has signs of TR, symptoms from TR, or prior HF hospitalization from TR. Patient must be on OMT per the local Heart Team at the time of TR assessment (TTE) for trial eligibility. OMT includes stable oral diuretic medications, unless patient has a documented history of intolerance
• Functional and/or degenerative TR graded as at least severe on a TTE (assessed by the Echo Core Lab (ECL) using a 5-grade classification proposed by Hahn et al. 2023
• The local Heart Team determines that the patient is appropriate for TTVR