Longterm outcomes in patients with acute and chronic myocardial injury

Background: Myocardial injury is defined as any cardiac troponin (cTn) level above the upper reference limit, namely, the 99th percentile value, and is caused by either ischemic or nonischemic events. The presence of acute myocardial injury (i.e., myocardial injury with a dynamic change in cTn levels) with evidence of myocardial ischemia is required for the diagnosis of myocardial infarction (MI). Nonischemic myocardial injury, defined as myocardial injury without evidence of ischemia, and type 2 MI are linked to a substantial risk of death and a poor prognosis. The purpose of this thesis was to study the characteristics, risks of death, and cardiovascular events in patients with type 1 MI, type 2 MI, acute nonischemic myocardial injury and chronic myocardial injury. In addition, this thesis aimed to investigate the impact of common cardiovascular medications within each type of myocardial injury.

Methods: Patients with myocardial injury (i.e., high-sensitivity cardiac troponin T (hscTnT)>14 ng/L) identified from a cohort of patients from the emergency department with at least one visit for chest pain at the Karolinska University Hospital 2011 and 2014 were included in the studies. The cohort was obtained from the local administrative database that includes all patients seeking medical attention in the ED, while additional data were obtained from national registers. Study I was performed to investigate the long-term outcome in patients (n=3 853) with hs-cTnT levels>14 ng/L who were categorized as: type 1 MI, type 2 MI, acute nonischemic myocardial injury, and chronic myocardial injury. Study II was performed to investigate the causes of death in patients with myocardial injury compared with those without myocardial injury (hs-cTnT<14ng/L), who died during follow-up (n=2 285). Study III was performed to investigate how the number of commonly prescribed cardiovascular drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, statins, and platelet inhibitors) impacts mortality and cardiovascular events in patients with different types of myocardial injury. Study IV was performed to investigate whether prescribed high-, medium-, and low-intensity statin therapy impacts risks and outcomes in patients with different types of myocardial injury.

Results: Patients with acute nonischemic myocardial injury and type 2 MI had a high risk of death, similar to patients with chronic myocardial injury, according to the findings of Study I. During a mean 4-year follow-up, nearly half of all patients in groups without type 1 MI died. Patients with nonischemic myocardial injury and patients with type 1 MI had similar high risk of cardiovascular death compared to patients with no myocardial injury. Patients with type 2 MI and chronic myocardial injury treated with 4 common cardiovascular drugs has a lower adjusted risk of death. Patients with nonischemic myocardial injury treated with two or three medications had a lower adjusted mortality risk compared to patients treated with zero or one medication. Patients with nonischemic myocardial injury and type 2 MI treated with high-intensity treatment had lower crude risks compared to patients treated with low-intensity treatment in corresponding groups, but estimates were not significant after adjusting for confounders.

Conclusions: Patients with nonischemic myocardial injury and type 2 MI have a high risk of all-cause mortality and share similar risks for cardiovascular death as patients with type 1 MI. Patients with nonischemic myocardial injury and type 2 MI may benefit from common cardiovascular medications. Currently no clinical recommendations are available for how patients with nonischemic myocardial injury or type 2 MI should be managed, and this warrants further attention.

List of scientific papers

I. Acute versus chronic myocardial injury and long-term outcomes. Erik Kadesjö, Andreas Roos, Anwar J. Siddiqui, Liyew Desta, Magnus Lundbäck, Martin J. Holzmann. Heart. 2019;105:1905–1912.
https://doi.org/10.1136/heartjnl-2019-315036

II. Causes of death in patients with acute and chronic myocardial injury. Erik Kadesjö, Andreas Roos, Anwar J. Siddiqui, Ulrik Sartipy, Martin J. Holzmann. The American Journal of Medicine. 2020;133:590–598.e2.
https://doi.org/10.1016/j.amjmed.2019.09.030

III. Treatment with cardiovascular medications: Prognosis in patients with myocardial injury. Erik Kadesjö, Andreas Roos, Anwar J. Siddiqui, Ulrik Sartipy, Martin J. Holzmann. Journal of the American Heart Association. 2021;10:e017239.
https://doi.org/10.1161/JAHA.120.017239

IV. Statin therapy and intensity: Prognosis in patients with myocardial injury. Erik Kadesjö, Andreas Roos, Anwar J. Siddiqui, Ulrik Sartipy, Martin J. Holzmann. The American Journal of Medicine. 2021;S0002-9343(21)00481-2.
https://doi.org/10.1016/j.amjmed.2021.07.005