HeartShare: Combining Omics, Deep Phenotyping, and Electronic Health Records for Heart Failure Subtypes and Treatment Targets

Prior treatment

• Prior history of solid organ transplantation.
• Prior history of mechanical circulatory support.
• Prior history of non-cardiac cirrhosis.
• Cardiac surgery, acute coronary syndrome, percutaneous coronary intervention, stroke, transient ischemic attack, or carotid intervention in the preceding 6 months prior to enrollment.
• Prior history of solid organ transplantation.
• Prior history of chronic infection (HIV, hepatitis C, hepatitis B, tuberculosis) unless treated and not clinically active in the opinion of the enrolling investigator.
• Prior history of mechanical circulatory support.
• Prior history of non-cardiac cirrhosis.

Other illness

• Primary cardiomyopathy (including amyloid, hypertrophic cardiomyopathy, cardiac sarcoidosis, hemochromatosis, or other infiltrative cardiomyopathies) or pulmonary arterial hypertension (WHO Group I, III, or IV pulmonary hypertension).
• Clinically significant valvular heart disease defined as:
  • Moderate to greater aortic stenosis, pulmonic stenosis, or tricuspid stenosis.
  • Any mitral stenosis.
  • Moderate or greater aortic regurgitation.
  • Greater than moderate mitral regurgitation.
• Any planned cardiac surgery or cardiac intervention in the next 3 months.
• Known symptomatic epicardial coronary artery disease that is not revascularized.
• Any condition that may preclude participation or adherence to the study protocol, in the opinion of the enrolling investigator.
• Current acute decompensated heart failure.

Lab values

• For non-HF group: any prior known left ventricular ejection fraction \<50%.
• Any prior known left ventricular ejection fraction \<40%, except if this occurred only in the setting of an acute tachycardia episode (e.g., acute atrial fibrillation).
• Estimated GFR \<20 ml/min/1.73m2 or currently on dialysis.

Other

• Inability to provide written consent to the study.
• Life expectancy estimated to be \< 1 year.
• Alternative primary reason for symptoms of shortness of breath and exercise intolerance in HFpEF participants in the opinion of the enrolling investigator.
• Any non-elective hospitalization in the preceding 2 weeks.
• Inability to provide written consent to the study.
• Currently pregnant.

• HF Inclusion Criteria (HeartShare Registry)
• Age ≥30 years.
• Prior diagnosis of HF in the EHR (any left ventricular ejection fraction).
  • Non-HF Group Inclusion Criteria (HeartShare Registry)
• Age ≥30 years.
• No known prior diagnosis of HF or use of loop diuretics.
• No known prior history of BNP \>100 pg/ml or NTproBNP \>300 pg/ml, if prior laboratory tests are available in the EHR.
  • HFpEF Inclusion Criteria (HeartShare Deep Phenotyping Cohort)
• Age ≥30 years.
• Left ventricular ejection fraction ≥50% measured by echocardiography.
• Definition of HFpEF: signs and symptoms of HF, NYHA functional class II-IV, and at least one of the following:
  • Elevated BNP (≥75 pg/ml in sinus rhythm or ≥225 pg/ml in atrial fibrillation/flutter) or NTproBNP (≥225 pg/ml in sinus rhythm or ≥675 in atrial fibrillation/flutter) at baseline. Choice of BNP or NTproBNP is based on availability at each clinical center.
  • Prior HF hospitalization (primary reason for the hospitalization is HF with elevated natriuretic peptide levels \[using the thresholds listed above\], requiring IV diuresis for HF, or pulmonary edema or pulmonary vascular congestion on chest radiography).
  • Elevated pulmonary capillary wedge pressure (PCWP) at rest (≥15 mmHg) or during exercise (≥25 mmHg for supine exercise or PCWP/cardiac output ratio ≥2 mmHg/L/min for upright exercise).
  • Elevated H2FPEF score26 (≥5) or HFA-PEFF27 score (≥5).
  • Non-HFpEF Group Inclusion Criteria (HeartShare Deep Phenotyping Cohort)
• Age ≥30 years.
• Left ventricular ejection fraction ≥50% measured by echocardiography.
• No known prior diagnosis of HF or use of diuretics for fluid management.
• No known prior history of BNP ≥75 pg/ml or NTproBNP ≥225 pg/ml, if prior laboratory tests are available in the EHR.
• BNP \<75 pg/ml or NTproBNP \<225 pg/ml at the time of screening. Choice of BNP or NTproBNP is based on availability at each clinical center.