Project Grant R01HL171150

SUDDEN DEATH RISK ASSESSMENT AND MECHANISTIC INSIGHTS IN ARRHYTHMIC MITRAL VALVE PROLAPSE USING CARDIAC MRI AND CIRCULATING PROTEOMIC BIOMARKERS - PROJECT SUMMARY: MITRAL VALVE PROLAPSE (MVP) IS A COMMON VALVULOPATHY AFFECTING 2-3% OF THE POPULATION AND NEARLY 200 MILLION INDIVIDUALS GLOBALLY. WHILE IT IS OFTEN BENIGN, A SUBSET OF PATIENTS WITH MVP MAY DEVELOP ARRHYTHMIAS, INCLUDING SUDDEN CARDIAC DEATH (SCD). ALTHOUGH THE ASSOCIATION BETWEEN MVP AND SCD WAS FIRST REPORTED DECADES AGO, THE RISK WAS INITIALLY BELIEVED TO BE SMALL; CONTEMPORARY OBSERVATIONAL STUDIES SUGGEST THAT SCD MAY BE A MORE COMMON SEQUELA IN MVP, WITH AN ESTIMATED YEARLY INCIDENCE BETWEEN 0.4 AND 1.9%. THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE RECENTLY CONVENED A WORKSHOP COMPOSED OF SUBJECT MATTER EXPERTS AND STAKEHOLDERS TO IDENTIFY RESEARCH NEEDS AND OPPORTUNITIES TO DEVELOP RECOMMENDATIONS FOR THE IDENTIFICATION AND TREATMENT OF INDIVIDUALS WITH MITRAL VALVE PROLAPSE, INCLUDING SUCH INDIVIDUALS WHO MAY BE AT RISK FOR SUDDEN CARDIAC ARREST OR SUDDEN CARDIAC DEATH. OUR CURRENT PROPOSAL IS DESIGNED TO ALIGN CLOSELY WITH THE PRIORITIES IDENTIFIED IN THE RECENT NIHBI WORKSHOP. SPECIFICALLY, OUR PROPOSAL HAS THREE AIMS: 1) PERFORM DEEP PHENOTYPING OF PATIENTS WITH MVP TO UNDERSTAND CHARACTERISTICS AND MECHANISMS ASSOCIATED WITH VENTRICULAR ARRHYTHMIAS; 2) STUDY A BLOOD BIOMARKERS PANEL (INCLUDING FDA-APPROVED AND NOVEL HIGH THROUGHPUT PROTEOMIC MARKERS) THAT COULD BE USED AS A SENSITIVE, COSTEFFECTIVE SCREENING STRATEGY TO IDENTIFY MVP PATIENTS WITH MYOCARDIAL FIBROSIS WHO ARE AT RISK FOR SCD; 3) BUILD A NOVEL SCD RISK PREDICTION MODEL IN MVP INCLUSIVE OF CMR EVIDENCE OF MYOCARDIAL FIBROSIS BY ASSEMBLING A LARGE OBSERVATIONAL MULTICENTER MVP REGISTRY WITH OVER 2,000 CONTRAST-ENHANCED CMRS AND LONGITUDINAL FOLLOW-UP FOR ARRHYTHMIC EVENTS.