Background: A vascular access blood flow (Qa) to cardiac output (CO) ratio greater than 0.3 increases the risk of high-output heart failure (HOHF). This study analyzed the characteristics and risk factors associated with a high Qa/CO ratio and effective CO (COef) in these patients over one year. Methods: This prospective study enrolled 142 hemodialysis (HD) patients, divided by the Qa/CO ratio. Baseline and one-year hemodynamics were measured: volume by bioimpedance, CO by echocardiography, Qa and brachial flow by transonic and ultrasound. Risk factors for HOHF were analyzed using receiver operating characteristic (ROC) curves and multivariable regression. Results: The study population was 66% male, mean age of 65, with 71% using arteriovenous fistulae (AVF) for vascular access. In the high Qa/CO group, cases of younger ages (62 vs. 67 years, p = 0.040) with upper arm access (73.1% vs. 32.8%, p < 0.001) were more prevalent, and diastolic blood pressure (DBP) was higher (76.8 ± 15.1 vs. 66.7 ± 14.4 mmHg, p = 0.002). Independent risk factors for high Qa/CO were elevated DBP (odds ratio [OR]: 1.080; 95% confidence interval [CI]: 1.028–1.134), upper arm access (OR: 8.113; 95% CI: 1.842–35.741), low resistive index (RI) (OR: 0.000; 95% CI: 0.000–0.417), and COef (OR: 0.164; 95% CI: 0.065–0.416). After one year, the high Qa/CO group showed significant increases in CO and COef (4.82 ± 1.25 L/min vs. 6.16 ± 2.05 L/min, p = 0.007, and 2.84 ± 0.95 L/min to 4.40 ± 1.89 L/min, p = 0.001, respectively). A baseline Qa cutoff value of 1.4 L/min demonstrated high diagnostic efficacy in identifying the high Qa/CO group. Conclusions: High Qa/CO ratios increase overt HOHF risk due to cardiac strain. This study reveals AV access-driven cardiac adaptations in patients with high Qa/CO and low COef, emphasizing the necessity for ongoing clinical and hemodynamic monitoring.

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