| Summary: | (1) Background: Cardiac resynchronization therapy (CRT) systems can be simplified by excluding the atrial lead and using a Ventricular-Dual-Dual (VDD) pacing lead. Possible disadvantages might include atrial undersensing and Ventricular-Ventricular-Inhibition (VVI) pacing. Because literature data concerning these systems are scarce, we analyzed their benefits and technical safety. (2) Methods: this retrospective study compared 50 patients implanted with VDD–CRT systems (group A), mainly because of unfavorable venous anatomy concerning the complication rate, with 103 subjects with Dual-Dual-Dual (DDD)–CRT systems (group B) implanted during 2000–2016 and 49 (group C) during 2016–2020. To analyze the functional parameters of the devices, we selected subgroups of 27 patients (subgroup A) and 47 (subgroup B) patients with VDD–CRT in 2000–2016, and 36 subjects (subgroup C) with DDD–CRT implanted were selected in 2017–2020. (3) Results: There was a trend of a lower complication rate with VDD–CRT systems, especially concerning infections during 2000–2016 (<i>p</i> = 0.0048), but similar results were obtained after rigorous selection of patients and employment of an upgraded design of devices/leads. With a proper device programing, CRT pacing had similar results, atrial undersensing being minimal (<i>p</i> = 0.65). For VDD-systems, VVI pacing was recorded only 1.7 ± 2.24% of the time. (4) Conclusions: In patients with a less favorable venous anatomy, VDD–CRT systems may represent a safe alternative regarding complications rates and functional parameters.
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