Characteristics and Outcomes of Venous and Arterial Thromboembolism Following Cardiac Transplant: A Multi-Institutional Retrospective Study

OBJECTIVES: Orthotopic heart transplant (OHT) is a treatment option for selected patients with advanced heart failure. As an open-heart surgery requiring cardiopulmonary bypass, OHT carries life-threatening risks including thrombosis. However, thrombotic complications following OHT are not well described. We used a large multi-center, real-world data repository to characterize the incidence and risk factors of postoperative thrombosis after OHT and describe its impact on survival.

METHODS: We used the TriNetX Research Network database to identify adult (≥ 18 years) patients who underwent OHT from 06/06/2004 to 06/05/2024. The TriNetX database is a global federated health research network that collects real-time electronic medical data across large healthcare organizations (HCOs). Using ICD-9 and ICD-10 codes, we identified comorbidities and thrombotic complications occurring within 30 days following OHT. We categorized thrombosis as venous (VTE) or arterial (ATE). VTE includes diagnosis codes for deep vein thrombosis (DVT), pulmonary embolism (PE), phlebitis/thrombophlebitis, and portal vein thrombosis. ATE includes diagnosis codes for myocardial infarction (MI), stroke, other arterial embolism and thrombosis, intracardiac thrombosis, and other acute ischemic heart disease. We assessed for risk factors associated with VTE and ATE occurrence using multivariable logistic regression, adjusting for baseline characteristics with p<0.05 on univariate analysis. We used Pearson's chi-square test to compare 30-day and 1-year mortality between patients who developed post-OHT VTE or ATE and patients who did not.

RESULTS: We identified 4,208 OHT recipients from 32 HCOs with a median age of 56.4 years (IQR 45.5-63.7 years) at the time of OHT. Patients were majority male (68.9%), White (61.5%), and not Hispanic/Latino (68.5%). Common comorbidities included primary hypertension (HTN, 63.9%), hyperlipidemia (HLD, 56.1%), chronic kidney disease (CKD, 56.3%), coronary artery disease (CAD, 52.2%), diabetes mellitus (DM, 48.8%), atrial fibrillation and flutter (AF, 46.0%), obesity (33.0%), sleep apnea (32.5%), and chronic lower respiratory disease (26.6%).

At 30 days post-OHT, the incidence of thrombosis overall was 21.1% (888) and mortality was 5.5% (233). VTE occurred in 670 (15.9%) patients; 507 (12.0%) developed DVT, 41 (1.0%) developed PE, 38 (0.9%) developed phlebitis/thrombophlebitis, and 4 (0.1%) developed portal vein thrombosis. Independent risk factors for VTE occurrence were history of HTN (odds ratio (OR) 1.29 [95% CI 1.05-1.58], p=0.018), HLD (OR 1.33 [95% CI 1.08-1.64, p=0.007), CKD (OR 1.25 [95% CI 1.04-1.51], p=0.021), AF (OR 1.21 [95% CI 1.02-1.44], p=0.032), and chronic lower respiratory disease (OR 1.26 [95% CI 1.05-1.51], p=0.014). There was no difference in mortality by VTE occurrence at 30 days (VTE 4.3% vs. non-VTE 5.8%, p=0.16) or at 1 year post-OHT (VTE 9.2% vs. non-VTE 11.1%, p=0.68).

Within thirty days after OHT, ATE occurred in 314 (7.5%) patients; 107 (2.5%) developed myocardial infarction (MI), 102 (2.4%) developed stroke, 79 (1.9%) developed other arterial embolism and thrombosis, 29 (0.7%) developed intracardiac thrombosis, and 29 (0.7%) developed other acute ischemic heart disease. History of CAD (OR 1.43 [95% CI 1.10-1.86], p=0.008) was independently associated with increased risk of ATE. Among those who developed ATE, mortality was significantly higher at 30 days (ATE 10.5% vs. non-ATE 5.1%, p<0.001) and at 1 year post-OHT (ATE 20.1% vs. non-ATE 10.2%, p<0.001).

CONCLUSIONS: Thrombotic complications after OHT are common, occurring in 21.1% of OHT recipients during the first 30 days after transplant. ATE has a negative impact on 30-day and 1-year survival. Assessment and management of chronic risk factors should be considered to mitigate morbidity and mortality in this population. Further studies are also needed to characterize the patterns of presentation and ideal course of treatment for OHT recipients who develop thrombosis.

Streiff:Attralus: Consultancy; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees. Chaturvedi:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.