Cardiogenic Shock and Sepsis-Related Mortality in the United States, 1999-2025: National Trends, Disparities, and Forecasts to 2040

Background: Cardiogenic shock (CS) complicated by sepsis is a life-threatening condition marked by circulatory collapse and systemic inflammation, with persistently high mortality despite critical care advances. National trends and disparities remain unclear. This study aimed to evaluate temporal mortality trends from 1999 to 2025 and project rates through 2040. Methods: We conducted a population-based study using U.S. mortality data (1999–2025) from the CDC WONDER database. Deaths among adults aged ≥25 years with CS and sepsis were identified using ICD-10 codes. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC). Forecasting models projected mortality trends through 2040. Results: From 1999 to 2025, 71,726 deaths occurred; 97.09% in medical facilities. Overall, AAMR rose from 0.65 to 2.16 (AAPC 5.01%, p < 0.001) and is projected to reach 3.62 by 2040. Men had higher mortality than women (2025: 2.78 vs 1.65; AAPC 5.06% vs 4.91%). In 2025, AAMR was 3.75 among NH Black individuals, 1.98 among NH White individuals, and 2.01 among Hispanic individuals. Adults ≥65 years had the highest CMR (7.50 in 2025; AAPC 4.63%), with the largest relative increase in ages 25–44 (AAPC 7.19%). Conclusion: CS with sepsis mortality increased significantly from 1999 to 2025, particularly among men, NH Black individuals, and adults ≥65 years. Although recent trends have stabilized, projections indicate continued increases through 2040, highlighting persistent and widening demographic disparities in the mortality burden.