In this study, we present a novel swine FTR model that uses a combination of radiofrequency ablation, atrial septostomy, and right atrial volume overload. Of the 12 pigs, one (8.3%) exhibited severe FTR, eight (66.7%) exhibited moderate TR, and three (25%) exhibited mild FTR after one month following the surgical procedure. Notably, the tricuspid annulus diameter, tenting height, RAA, and RV significantly increased compared with the preoperative measurements, highlighting the effectiveness and reproducibility of this innovative modeling approach.

Radiofrequency ablation was performed on the left and right endocardium to induce premature atrial beats in the swine subjects. During the study, all swine subjects experienced premature atrial contractions, with an average of 510 ± 225 occurrences per hour as monitored by an ECG. This can be attributed to scar formation in the atrium. A previous study reported that radiofrequency ablation creates deep and wide myocardial lesions when the electrode contacts the endocardium. This leads to contraction-band necrosis and subsequent edema, eventually becoming a scar [8]. The occurrence of heart rhythm disturbances is closely associated with the extent of myocardial injury; in this case, premature atrial contractions were triggered by endocardial ablation [9,10,11]. The persistence of premature atrial contractions subsequently results in hemodynamic disorders in both the left and right atria, leading to volume overload and the development of FTR.

A left-to-right shunt was created through transseptal puncture, radiofrequency ablation, and balloon dilation, allowing stable interatrial communication and blood flow from the LA to the RA. Radiofrequency ablation around the fenestration rim resulting from balloon atrial septostomy prevented spontaneous communication closure. Additionally, radiofrequency ablation of the fossa ovalis in our study reduced local elastic recoil. Using these methods, we established an artificial left-to-right shunt, which led to volume overload in the RA and subsequent enlargement of the RA, ultimately inducing TR. Patients with atrial septal defects are predisposed to FTR, and transcatheter atrial septal defect closure has been shown to significantly reduce FTR occurrence, which is consistent with the findings of previous studies [12,13,14,15]. Therefore, creating an artificial left-to-right shunt is a valuable approach to induce FTR in swine models [16]. Additionally, to the blood volume in the RA, sterile saline was administered to the swine subjects at a daily volume of 2000 mL over 1 month.

Using the composite measures described in this study, we successfully developed a valid and effective FTR model. Echocardiography performed one-month postoperatively confirmed the presence of TR in all swine subjects. Echocardiography and necropsy revealed a significantly larger tricuspid annulus, further supporting the establishment of a TR model. Importantly, our TR model was established through transcatheter intervention without mechanical disruption of the tricuspid valvular complex. Previous studies have employed transthoracic surgery or transcatheter intervention techniques that artificially damage the tricuspid valve complex, including the leaflets, papillary muscles, and tendon cords [17,18,19]. In contrast, our FTR model represents a more physiological approach, closely resembling the scenario observed for FTR. This distinction makes our model more realistic and clinically relevant for investigating TR in patients with FTR.

Previous studies have attempted to develop FTR models. Marcin et al. [6] used rapid ventricular pacing to induce FTR in ovine subjects. The procedure involved implanting a pacemaker with an epicardial left ventricular lead and placing sonomicrometry crystals on the right ventricle, along with telemetry pressure sensors on the left and right ventricles. The ovine subjects were paced at 220–240 beats/min until TR was observed. While this approach resulted in reliable and reproducible FTR models, it is important to note that the significant biventricular dysfunction and remodeling observed limits its applicability in reflecting the clinical condition of patients with end-stage heart failure who require mechanical support. In addition to in vivo models, researchers have developed in vitro FTR models. One such model is the swine heart bench model, which is considered to be a reliable system for simulating the pathophysiology of FTR [20]. In this method, a swine heart was mounted on a rigid support and immersed in a saline basin. A pump was used to convey saline from the basin to the right ventricle, thereby inducing FTR. This technique offers a simple and cost-effective approach for simulating FTR and can be used as a complementary approach for evaluating new technologies and therapies. Despite previous research, a viable in vivo model that accurately simulates atrial FTR in clinical settings remains to be established.

This study successfully established an atrial FTR model in swine subjects using a combination of catheter radiofrequency ablation, interatrial fistulation, and right atrial overload to induce right atrial dysfunction, which would cause right atrial myocardial fibrosis and cardiomyocyte hypertrophy, leading to RA enlargement [21]. Subsequently, an increase in the tricuspid annulus size and the development of TR were observed. Notably, many patients with FTR and atrial dysfunction also experienced atrial fibrillation and significant atrial enlargement [22, 23]. Therefore, our model successfully emulates the pathophysiology of FTR in this patient population, providing a reliable and effective platform for further research on simulating clinical FTR. By utilizing this model, we aimed to gain a deeper understanding of the underlying mechanisms involved in FTR and identify potential therapeutic targets for treating this condition.

This study has some limitations that must be acknowledged. First, the follow-up duration of the study may have been insufficient as it only spanned 1 month. More severe FTR would be observed with a longer follow-up duration. To address this potential limitation, we are conducting a study with a larger sample size and longer follow-up duration. Second, the development of FTR in our swine model required multiple treatments, including catheter radiofrequency ablation and interatrial fistulation. This complex approach requires a steep learning curve and high degree of expertise and experience on the part of operators. Finally, developing FTR models using these procedures incurs relatively high costs. This may limit the feasibility of the widespread use of our models; however, we believe that the benefits of developing accurate and reliable FTR models outweigh the cost limitations.

In conclusion, we successfully developed a novel swine FTR model using a combination of catheter radiofrequency ablation, interatrial fistulation, and right atrial volume overload. Our FTR model was demonstrated to be both effective and reliable, making it a valuable tool for studying the pathophysiology of FTR.