Electrogram-Guided Myocardial Advanced Phenotyping

Non-Ischemic Cardiomyopathy (NICM) is a common cause of heart failure (HF) and death. NICM is
a heterogeneous entity, and specific etiologies are infrequently identified. In part due to
limited disease characterization, specific treatments are lacking for most of the different
underlying causes of NICM. Depending on the cohort, 30-70 percent of patients with new-onset
NICM develop persistent systolic dysfunction despite guideline-directed medical therapy, and
these patients have high rates of subsequent morbidity and resource utilization.

Current guidelines support the use of endomyocardial biopsy (EMB) in patients with both
new-onset and persistent cardiomyopathy. However, EMB is underutilized in these populations
due to its low diagnostic yield. A combination of sampling error resulting from standard
fluoroscopy-guided EMB in disease entities with patchy myocardial involvement and rudimentary
tissue phenotyping of the specimens which are obtained contribute to this low diagnostic
yield. In recent years, there has been increasing interest in the use of electro-anatomic
mapping (EAM) to help identify areas of myocardium with discrete pathology based on
abnormalities in intra-cardiac electrogram voltage and morphologies. Therefore, the primary
objective of this protocol is to provide definitive evidence that EAM-guided biopsy leads to
a superior diagnostic yield compared with conventional fluoroscopy-guided biopsy in patients
with new-onset and persistent NICM.

Inclusion Criteria:

1. Age ≥ 18 years

2. New onset NICM as defined by the presence of left ventricular dysfunction (LVEF < 45%
by echocardiography and/or MRI), with symptoms or signs of HF (dyspnea, orthopnea,
edema, ascites, rales or pulmonary vascular congestion on chest radiography) of less
than 3 months in duration.

3. Persistent recent onset NICM as defined by the LVEF and signs/symptoms in #2 above
with persistence of the LVEF < 45% despite evidence-based treatment for HF with
reduced LVEF for 2 to 6 months.

4. Willingness to provide informed consent

Exclusion Criteria:

1. Prior diagnosis of HF or documented LVEF < 45% more than 6 months prior to enrollment.

2. Coronary artery disease, either by history or as determined by coronary angiography
demonstrating hemodynamically significant lesions deemed sufficient to potentially
contribute to left ventricular dysfunction.

3. Ongoing hemodynamically significant arrhythmias deemed to be an independent cause of
HF decompensation

4. Constrictive pericarditis or tamponade

5. Complex congenital heart disease

6. History of malignancy with treatment by anthracyclines or other known cardiotoxic
chemotherapeutic agents

7. More than mild aortic or mitral stenosis

8. Intrinsic (prolapse, rheumatic) valve disease with severe mitral, aortic or tricuspid
regurgitation

9. Primary hypertrophic cardiomyopathy

10. Untreated thyroid disease

11. Severe nutritional deficiency

12. Severe uncontrolled hypertension

13. Sepsis, active infection (excluding cystitis) or other comorbidity driving the HF
decompensation

14. History of cardiac transplantation

15. Acute or chronic severe liver disease as evidenced by any of the following:
encephalopathy, variceal bleeding, INR > 1.5 in the absence of anticoagulation
treatment

16. Inability to comply with planned study procedures