Abstract Body: Introduction:
Hypertension (HTN) is prevalent in non-ischemic cardiomyopathy (NICM) and a known risk factor for ischemic cardiomyopathy (ICM), independently contributing to adverse cardiovascular outcomes. However, limited data exist comparing its impact on outcomes between NICM and ICM populations.

Hypothesis:
This study aims to compare the outcomes of hypertension in patients with NICM versus ICM.

Methodology:
This retrospective cohort study used the TriNetX Global Collaborative Network to analyze adults aged ≥18 between January 2007 and May 2025. Two matched cohorts were evaluated: 1,023,462 patients with NICM and HTN, and an equal number with ICM and HTN. The mean age at diagnosis was 66 years; 57% were male, 39% female, and 4% had unknown gender. Median follow-up was 960 days for the NICM group and 944 days for the ICM group.

Results:
Cohort 1 (NICM and HTN) exhibited significantly higher risks across all cardiovascular outcomes compared to Cohort 2 (ICM and HTN). The all-cause mortality risk was 23.3% in Cohort 1 versus 18.9% in Cohort 2, with a Risk Ratio (RR) of 1.234 (95% CI: 1.227–1.241), Hazard Ratio (HR) of 1.248 (95% CI: 1.241–1.256), and p < 0.0001. Heart failure was observed in 60.4% of Cohort 1 compared to 31.6% in Cohort 2, with an RR of 1.914 (95% CI: 1.908–1.921), HR of 2.534 (95% CI: 2.524–2.545), p < 0.0001. Atrial fibrillation/flutter occurred in 39.6% of Cohort 1 versus 24.7% in Cohort 2, with an RR of 1.602 (95% CI: 1.595–1.609), HR of 1.787 (95% CI: 1.778–1.796), p < 0.0001. Ventricular tachycardia risk was 13.9% in Cohort 1 compared to 5.5% in Cohort 2, with an RR of 2.533 (95% CI: 2.509–2.557), HR of 2.674 (95% CI: 2.648–2.700), p < 0.0001. Lastly, ventricular fibrillation/flutter occurred in 2.6% of Cohort 1 versus 1.0% in Cohort 2, with an RR of 2.474 (95% CI: 2.419–2.530), HR of 2.513 (95% CI: 2.456–2.571), p < 0.0001. Kaplan-Meier survival analyses showed statistically significant differences across all outcomes (p < 0.0001).

Conclusion:
Despite adjustment for hypertension, patients with NICM exhibited significantly higher risks of all-cause mortality, heart failure exacerbations, atrial fibrillation, and ventricular arrhythmias compared to those with ICM. These findings indicate a greater long-term disease burden among individuals with NICM and underscore the need for tailored management strategies and enhanced surveillance in this high-risk population.