US Benchmarking Clinical Study

Inclusion criteria

• Inclusion Criteria Common to all three Study Arms:
• Male or female age ≥ 60 years
• Signed informed consent and able to comply with protocol
• Inclusion Criteria Common to the Heart Failure with non-reduced left ventricular ejection fraction (LVEF) with or without transthyretin amyloid cardiomyopathy (ATTR-CM) Arms:
• Patients meeting the Universal Definition of Heart Failure \& HeartShare study criteria.
• LVEF \>40% on the last available imaging study
• Left ventricular hypertrophy (LVH) defined as left ventricular mass index (mass/BSA) in female \> 95 g/m², in male \> 115 g/m² according to American Society of Echocardiography/European Association of Cariology (ASE/EAC) guidelines42 OR as interventricular septum (IVS) thickness ≥12 mm
• Inclusion criterion specific to HF with non-reduced LVEF without ATTR-CM Arm:
• Negative (grade 0) Pyrophosphate (PYP) scintigraphy within 24 months prior to the enrolment in the study OR Simple Score \<643 OR negative endomyocardial biopsy
• Inclusion criterion specific to HF with non-reduced LVEF with ATTR-CM Arm:
• ATTR-CM objectively confirmed and classified at any time prior to the enrollment in the study, with monoclonal protein AL amyloidosis ruled out, according to American Heart Association (AHA) 2020 criteria
• Inclusion criteria in Control Subjects:
• No diagnosis of HF or cardiomyopathy according to the universal definition of Heart Failure
• No diagnosis of Transthyretin amyloid cardiomyopathy (ATTR-CM) or Amyloid light-chain (AL) amyloidosis

Exclusion criteria

• Exclusion criteria common to the three arms:
• Pregnant OR pre-menopausal woman
• Vulnerable patients
• Acute Coronary Syndrome within 30 days
• Heart rate greater than 130 beats/minute at the time of the measurements
• Atrial fibrillation or flutter at the time of SWV measurement (history of AF is authorized provided they patient is in sinus rhythm at the time of the measurements)
• Any clinically significant cardiac arrhythmia at the time of SWV measurement
• Poor echogenicity preventing accurate ultrasound measurements
• Patients with segmental wall motion abnormalities thought to be due to myocardial infarction.
• Severe mitral or aortic valve disease (regurgitation or stenosis) excluded if the cause is other than ATTR (e.g., prolapse, endocarditis, prosthetic valve.)
• Severe tricuspid valve disease (regurgitation or stenosis) excluded if the causes are other than ATTR.
• Distance from skin to IVS ≥ 8 cm
• Any prosthetic mechanical valve
• Patients with mechanical cardiac assist devices other than pacemakers or defibrillators
• Heart, lung, liver or kidney transplant history or expected in the next year
• Severe renal impairment with eGFR \< 15 mL/min/1.73m² or end-stage renal disease or patient on dialysis.
• Presence of any competing life-threatening risk over the next 12 months
• Complicated uncontrolled diabetes mellitus HbA1c ≥9% with target organ damage.
• Uncontrolled and persistent high-blood pressure with diastolic pressure \> 100 mmHg or systolic pressure \> 160 mmHg at the time of the measurement.
• Acute decompensated state such as volume overload, etc. in the opinion of the study investigator
• Skin abnormalities, infections, or open wounds at the site of the SVW measurement
• Liver disease, at least moderate
• Exclusion criteria in both the HF with non-reduced LVEF with or without ATTR-CM Arms:
• Known inherited cardiomyopathy, infiltrative cardiomyopathy (other than ATTR-CM for the study arm for ATTR-CM), cardiomyopathy from muscular dystrophies, cardiomyopathy with reversible causes (e.g., stress cardiomyopathy), hypertrophic cardiomyopathy or known pericardial constriction
• History of treatment for ATTR-CM with Transthyretin (TTR) depleters
• Exclusion criteria Specific to Control Subjects:
• Any diagnosis of cardiomyopathy or HF, whatever the cause46
• LVH based on LV mass index female \>95 g/m², in male ≥115 g/m² OR IVS thickness ≥12 mm unless thought to be due to athlete's heart