Prevention of myocardial functional deterioration and sudden cardiac death among individuals of intermediate risk remains one of the most elusive frontiers of contemporary medicine. While most of these individuals are known to have had contact with the medical system, they are frequently not considered to be at high risk until far advanced along one or multiple disease processes leading to irreversible myocardial loss and electric instability. The goal of this proposal is to determine the prognostic power of combining specific measures of ventricular architecture, myocardial structure and electrical function for the early identification of individuals at risk to develop ventricular arrhythmias and progressive myocardial failure leading to severe cardiovascular outcomes and death.

During C-TRIP Stage 1 we refined a risk stratification algorithm based on the electronic analysis of 69,088 routine 12-lead ECGs performed in a large medical institution during a 6 month period by combining previously established indices of abnormal repolarization (wide QRS-T angle) with validated measures of myocardial damage (Selvester QRS score). Among patients considered at risk, 4.9% had perished 18 months later and among the survivors those > 70 years of age or with LV ejection fraction ≤ 35%, or at a high risk of dying within 3 years from cancer, end stage cardiac, pulmonary, renal, immunologic or neurologic diseases, were excluded using a simple and reproducible screening arborescence based on the digital medical record. From the pool of remaining at risk patients derived from the application of the same screening methods in three other similarly large academic institutions, a sample of 1100 individuals will be recruited for further risk stratification as participants of the C-TRIP Stage 2 prospective study. For C-TRIP Stage 2, patients will undergo detailed phenotypic studies including contrast-enhanced cardiac MRI, ECG Holter recordings at rest and during a 6 minute walk, signal averaged ECG and biomarkers of inflammation, myocardial ischemia and stress, as well as indices of collagen synthesis and turnover. Patients will be followed for 3 years for the development of a combined clinical outcome including mortality (all cause, cardiac and sudden cardiac death) and hospitalization for non-fatal myocardial infarction, acute coronary syndromes, ventricular arrhythmias and heart failure. From the combination of selected phenotypic markers of poor outcome, a risk score will be developed and used for the design of prophylactic strategies aimed at curbing premature sudden cardiac death and end-stage cardiac disease among patients currently classified as having intermediate levels of risk.

Inclusion Criteria:

• general hospital population with routine 12-lead ECG with abnormal repolarization (wide QRS-T angle>100°) with validated measures of myocardial damage (Selvester QRS score>5)

Exclusion Criteria:

• LVEF <35%
• age>70 years
• eGFR<45mL/min
• no ICD or PM
• no high risk of dying within 3 years from cancer, end stage cardiac, pulmonary, immunologic or neurologic diseases

We refined a risk stratification algorithm based on the electronic analysis of 69,088 routine 12-lead ECGs performed in a large medical institution during a 6 month period by combining previously established indices of abnormal repolarization (wide QRS-T angle) with validated measures of myocardial damage (Selvester QRS score).