Background/Objectives: Cardiovascular diseases are the most important cause of mortality in chronic obstructive pulmonary disease (COPD). Speckle-tracking echocardiography (2D-STE) can be used for assessing atrial and ventricular function, and its role in COPD is underexplored. The main objective of this study was to investigate prognostic associations in patients with COPD using 2D-STE echocardiography and laboratory biomarkers. Methods: The study included 70 participants, divided into two groups: 55 patients diagnosed with COPD and 15 healthy controls. All four cardiac chambers were analyzed with standard ultrasound and 2D-STE techniques. We measured NT-proBNP and several oxidative stress biomarkers: reduced glutathione (GSH), the GSH/GSSG ratio, malondialdehyde (MDA), and Caspase-3. Results: An NT-proBNP level above 325 pg/mL independently predicts advanced COPD stages (GOLD grades 3 and 4), with statistically significant results at a 95% confidence interval (CI) (p = 0.001). Additionally, 2D-STE identified reduced right ventricular (RV) and left ventricular (LV) strain in COPD patients before changes in LV ejection fraction. RV and LV strain measurements (RV4CLS < −16.15%, RVFWSL < −18.6%, LV GLS < −19.45%) along with PASP > 37.5 mmHg are independent predictors of advanced COPD stages, demonstrating significance at a 95% CI (p = 0.001). A positive correlation was observed between NT-proBNP, ultrasound parameters assessing RV systolic function, LV longitudinal strain impairment, and PASP. Conclusions: NT-proBNP serves as an independent biomarker of pulmonary hypertension and secondary right heart overload and independently predicts advanced COPD stages (GOLD grades 3 and 4) alongside RV and LV strain measurements.