De-StunHeartAttacks · Re-defining clinical care and reasoning in ST-elevation myocardial infarction (STEMI) by shifting focus to ischemic myocardial stunning - Mechanisms prognostic implications and a new treatment

Acute ischemic heart failure (AIHF) after ST-elevation myocardial infarction (STEMI) is a common and life-threatening condition for which the prognosis has not improved over the past decade, and for which no effective treatment option exists. Women, who have been underrepresented in most STEMI studies are more likely than men to develop AIHF after STEMI. My research aims to shift focus from traditional treatment targets (increased cardiac work and maintenance of blood pressure) to manipulation of myocardial stunning, the physiological phenomenon in which viable myocardium suddenly lose its function (becomes ‘stunned’) when exposed to a stressor (e.g. ischemia). Specifically, I aim to: 1) compare how stunning and propensity for AIHF affect prognosis for women vs. men with STEMI – using causal mediation analysis applied to a unique nationwide STEMI cohort (around 40,000 patients); 2) prospectively compare the rate of stunning resolution in STEMI patients with vs. without microvascular obstruction, in patients with STEMI vs. patients with takotsubo (another form of myocardial stunning with more favorable prognosis), and for women with STEMI vs. men with STEMI; 3) conduct a randomized controlled trial to assess the optimal timing of initiation of guideline-directed heart failure medications after STEMI; and 4) determine if pre-existing takotsubo-like stunning is protective in experimental AIHF. If my main hypothesis is correct, my this project could change the way researchers and clinicians approach the pathophysiology and treatment in STEMI. Irrespective of whether my main hypothesis is correct, my research proposal is designed to provide important insight into the pathophysiology and prognosis of myocardial stunning in STEMI, with a clear sex perspective that can help mitigate the sex gap in the level of evidence supporting the use and benefit of current treatments for STEMI.