Substance Use Disorder and Acute Myocardial Infarction Readmissions After Heart Failure Hospitalization: A Nationwide Analysis of 31.9 Million U.S. Hospitalizations

Background Prior work identified substance use disorder (SUD) as the only psychiatric comorbidity independently associated with increased cardiovascular (CV) readmission risk after heart failure (HF) hospitalization. This study aims to characterize the clinical profile of HF patients with co-occurring SUD; identify the CV diagnoses associated with the greatest risk of readmission; and compare short- and long-term readmission patterns. Methods We conducted a retrospective cohort study using the 2016-2022 Nationwide Readmissions Database and included adults hospitalized for HF with and without SUD. The primary outcomes were the CV diagnoses associated with the greatest risk of readmission at 30 days and 1 year. A secondary, substance-specific analysis stratifying SUD into individual substance categories was performed to assess their associations with myocardial infarction (MI) readmission. Results Among 31,886,859 HF hospitalizations, acute MI conferred the greatest SUD-associated risk of CV readmission at both 30 days (aHR 1.16) and 1 year (aHR 1.14). Cannabis (aHR 1.21 at 30 days; 1.22 at 1 year) and other stimulant use, including amphetamine or methamphetamine (aHR 1.26 at 30 days; 1.27 at 1 year) yielded the highest sustained MI readmission risk. Cocaine emerged as an additional risk factor at 1 year (aHR 1.17). p<.001 for all. Conclusion Acute MI is the most clinically consequential CV readmission diagnosis among HF patients with SUD. The excess risk is driven primarily by cannabis and stimulant use, with cocaine contributing longer-term risk. These findings highlight the need for integrated CV and addiction-focused care pathways to reduce preventable ischemic events in this high-risk population.