Doxorubicin (DOX) chemotherapy in cancer patients increases the risk of the occurrence of cardiac dysfunction and even results in congestive heart failure. Despite the great progress of pathology in DOX-induced cardiomyopathy, the underlying molecular mechanisms remain elusive. Here, we investigate the protective effects and the underlying mechanisms of melatonin in DOX-induced cardiomyopathy. Our results clearly show that oral administration of melatonin prevented the deterioration of cardiac function caused by DOX treatment, which was evaluated by left ventricular ejection fraction and fractional shortening as well as cardiac fibrosis. The ejection fraction and fractional shortening in the DOX group were 49.48% and 25.5%, respectively, while melatonin treatment increased the ejection fraction and fractional shortening to 60.33 and 31.39 in wild-type mice. Cardiac fibrosis in the DOX group was 3.97%, while melatonin reduced cardiac fibrosis to 1.95% in wild-type mice. Sirt3 is a mitochondrial deacetylase and shows protective effects in diverse cardiovascular diseases. Therefore, to test whether Sirt3 is a key factor in protection, Sirt3 knockout mice were used, and it was found that the protective effects of melatonin in DOX-induced cardiomyopathy were partly abolished. Further analysis revealed that Sirt3 and its downstream molecule TFEB were downregulated in response to DOX treatment, while melatonin administration was able to significantly enhance the expressions of Sirt3 and TFEB. Our in vitro study demonstrated that melatonin enhanced lysosomal function by increasing the Sirt3-mediated increase at the TFEB level, and the accumulation of autolysosomes induced by DOX treatment was attenuated. Thus, autophagic flux disrupted by DOX treatment was restored by melatonin supplementation. In summary, our results demonstrate that melatonin protects the heart against DOX injury by the restoration of autophagic flux via the activation of the Sirt3/TFEB signaling pathway.

Background: Transcatheter treatments of tricuspid regurgitation (TR) have been emerging as alternatives for high-risk patients. In contrast to the immobilization of the common transcatheter tricuspid device, using a radial force-independent stent valve device at the native tricuspid annular site has several distinct advantages. Case summary: A 76-year-old patient with renal insufficiency who underwent mechanical mitral valve replacement in 2001 and transcatheter aortic valve replacement in 2021 due to severe aortic stenosis presented with chest pain and shortness of breath. Echocardiography suggested that the flow velocities of the mitral mechanical valve and aortic prosthetic valve were both within the normal range, with no significant paravalvular regurgitation; the tricuspid valve exhibited massive regurgitation (VMAX 258 cm/s, PGMAX 27 mmHg). Due to the high surgical risk, we simulated the procedure with a three-dimensional (3D)-printed model and performed transcatheter tricuspid valve replacement using a LuX-Valve (Ningbo Jenscare Biotechnology Co., Ningbo, China). Discussion: We describe transcatheter tricuspid valve replacement using the LuX-Valve and preprocedural guidance with 3D printing. Postprocedural TR was significantly reduced, indicating that 3D printing plays an important role in preprocedural guidance and that the LuX-Valve was safe and practicable for tricuspid valve replacement.

Background: Transcatheter mitral valve-in-ring replacement (TMViR) is an emerging alternative for patients with recurrent mitral regurgitation (MR) after a prior failed annuloplasty ring. However, intraoperative common issues and complications remain to be addressed. Case summary: We describe the case of a 67-year-old male patient who underwent surgical mitral concomitant tricuspid annuloplasty repair 7 years ago who developed recurrent severe MR (New York Heart Association functional class IV). To avoid a high-risk surgical reoperation, we chose to perform a TMViR using an innovative dedicated device—the Mi-thos system—via a transapical approach. A patient-specific, 3-dimensional printed model was used to guide the procedure to avoid potential challenges. The procedure was performed successfully, and the patient exhibited symptomatic improvement. Conclusions: This case report highlights the first use of the innovative Mi-thos system in a TMViR procedure. The findings demonstrate the feasibility and safety of utilizing the Mi-thos system, guided by 3-dimensional printing technology, for patients who have experienced recurrent mitral regurgitation MR following a failed annuloplasty ring.

Background: Transcatheter aortic valve replacement (TAVR) using the J-Valve system provides a solution for patients with aortic regurgitation (AR). However, it remains unclear whether its coaxiality performance is related to procedural complications. Aim: Our goal was to improve the efficacy and accuracy of TAVR in patients with AR by adjusting J-Valve coaxiality using three-dimensional printing (3DP). Methods: This multicenter, prospective study included 612 patients with AR who underwent transapical TAVR. Of these, 228 patients were assigned to the 3DP group, in which the insertion angle and implantation depth were pre-determined. The coaxiality index was calculated using the distances from the bottom of the bioprosthesis to the base of the three cusps. Results: Compared to the non-3DP group, the 3DP group demonstrated better coaxiality performance (coaxiality index: 3.4 ± 1.7 vs. 4.0 ± 2.1; coaxiality angle: 10.5 ± 3.7° vs. 12 ± 4.2°; both p<0.001). Post-operative coaxiality index showed a strong correlation with the coaxiality angle (correlation coefficients: 0.85 in the 3DP group and 0.88 in the non-3DP group). The procedural success rate was higher in the 3DP group (100% vs. 96.4%; p=0.008). Paravalvular leakage (PVL) occurred less frequently in the 3DP group (mild PVL: 3.51% vs. 18.2%; p<0.001; moderate PVL: 0% vs. 1.04%; p<0.001). Multivariable analysis identified the coaxiality index, coaxiality angle, and horizocardia as independent predictors of PVL. Conclusion: PVL incidence after TAVR can be reduced through pre-operative simulations that adjust coaxiality using 3DP. Relevance for patients: The high incidence of PVL in transapical TAVR with the J-Valve is associated with coaxiality after bioprosthesis implantation. This study suggests that adjusting coaxiality using pre-procedural 3DP simulations may effectively reduce PVL incidence and other procedural complications during transapical TAVR. In the future, randomized clinical trials will be needed to evaluate the efficacy and accuracy of pre-procedural 3DP simulations and the coaxiality index in treating patients with pure AR undergoing transapical TAVR.