Transcatheter tricuspid valve interventions: Current devices and clinical evidence.

The tricuspid valve is known as "the forgotten valve". Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. TR is often late in the course of the disease when it becomes symptomatic, often being a marker of late-stage chronic heart failure with a poor prognosis and high mortality rate at long-term follow-up. Despite the clear correlation between TR and mortality, most TR patients are under-treated. Neither pharmacologic nor surgical treatment demonstrates a significant survival benefit. Isolated tricuspid valve surgery has the highest mortality rate of all valve surgeries. Therefore, there is an urgent clinical need for minimally invasive therapies to meet the needs of patients with TR. In recent years, a variety of transcatheter tricuspid valve interventions representing less invasive alternatives to surgery have shown promising results, which bring hope to patients with severe TR. The purpose of this review is to provide a complete and updated overview on current transcatheter tricuspid valve interventions and clinical evidence.

Potent cancer therapy by liposome microstructure tailoring with active-to-passive targeting and shell-to-core thermosensitive features.

Liposomes have been widely studied as drug carriers for clinical application, and the key issue is how to achieve effective delivery through targeting strategies. Even though certain cell-level targeting or EPR effect designs have been developed, reaching sufficient drug concentration in intracellular regions remains a challenge due to the singularity of functionality. Herein, benefiting from the unique features of tumor from tissue to cell, a dual-thermosensitive and dual-targeting liposome (DTSL) was creatively fabricated through fine microstructure tailoring, which holds intelligent both tissue-regulated active-to-passive binding and membrane-derived homologous-fusion (HF) properties. At the micro level, DTSL can actively capture tumor cells and accompany the enhanced HF effect stimulated by self-constriction, which achieves a synergistic promotion effect targeting tissues to cells. As a result, this first active-then passive targeting process makes drug delivery more accurate and effective, and after dynamic targeting into cells, the nucleus of DTSL undergoes further thermally responsive contraction, fully releasing internal drugs. In vivo experiments showed that liposomes with dual targeting and dual thermosensitive features almost completely inhibited tumor growth. Summarized, these results provide a reference for a rational design and microstructural tailoring of the liposomal co-delivery system of drugs, suggesting that active-to-passive dual-targeting DTSL can function as a new strategy for cancer treatment.

Risk stratification by systemic manifestations secondary to hemodynamic disorders of patients with severe tricuspid regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. METHODS: Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. RESULTS: A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62-83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183-324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). CONCLUSIONS: Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.

Long-Term Outcomes of Bioprosthetic and Mechanical Tricuspid Valve Replacement after Left-Sided Valves Surgery.

PURPOSE: This study aimed to show the outcomes of isolated tricuspid valve replacement (ITVR) after left-sided valve surgery (LSVS). METHODS: Patients who underwent ITVR after LSVS were divided into bioprosthetic tricuspid valve (BTV) and mechanical tricuspid valve (MTV) groups. Clinical data were collected and analyzed between groups. RESULTS: 101 patients were divided into BTV (n = 46) and MTV (n = 55) groups. The mean ages of the BTV and MTV groups were 63.4 ± 8.9 and 52.4 ± 7.6 years, respectively (P <0.01). There was no significant difference in 30-day mortality (BTV 10.9% vs. MTV 5.5%), early postoperative complications, and long-term tricuspid valve (TV)-related adverse events between these two groups. New-onset renal insufficiency was an independent risk factor for early mortality. Survival rates in the BTV group were 94.8% ± 3.6%, 86.5% ± 6.5%, and 54.2% ± 17.6% and in the MTV group were 96.0% ± 2.8%, 79.0% ± 7.4%, and 59.4% ± 14.8% at 1, 5, and 10 years, respectively (P = 0.826). CONCLUSION: The TV prosthesis selection in ITVR after LSVS seems to not affect 30-day mortality and early postoperative complications. Long-term survival and the occurrence of TV-related events were also comparable between these two groups.

Prognostic Value of Systemic Inflammation Response Index in Acute Type A Aortic Dissection.

BACKGROUND: The study aimed to evaluate the prognostic value of preoperative systemic inflammation response index (SIRI) for acute type A aortic dissection (ATAD) following open surgery. METHODS AND RESULTS: Totally, 410 ATAD patients underwent open surgery from 2019 to 2021 were enrolled in the study. Among the patients, the in-hospital mortality was 14.4%. Cox regression (95%CI 1.033-1.114p < 0.001) and receiver operating characteristic curve analysis (AUC = 0.718, p < 0.001) demonstrated the prognostic role of SIRI for in-hospital mortality after surgery. The optimal cut-off value of SIRI for in-hospital mortality was identified as 9.43 by maximally selected Log-Rank statistics. The patients were divided into high SIRI group (SIRI ≥ 9.43) and low SIRI group (SIRI < 9.43)) after the linear inverse relationship between SIRI and hazard ratio for in-hospital mortality was demonstrated by restricted cubic spline analysis (p = 0.0742). The Kaplan-Meier analysis illustrated that in-hospital mortality increased significantly in high SIRI group (p < 0.001). In addition, elevating SIRI was significantly associated with the incidence of coronary sinus tear (95%CI 1.020-4.475p = 0.044). Furthermore, the incidence rate of postoperative complications including renal failure (p < 0.001) and infection (p = 0.019) was higher in high SIRI group. CONCLUSION: The study indicated that preoperative SIRI could provide strong prognostic value for in-hospital mortality in ATAD patients following open surgery. Thus, SIRI was a promising biomarker for risk stratification and management prior to open surgery.

Levels of preoperative cerebrospinal fluid pro-inflammatory mediators and chronic pain after total knee arthroplasty surgery.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre- and postsurgical chronic pain in TKA surgery. METHODS: The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL-6, IL-8, TNF, fractalkine, and CSF-1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery. RESULTS: While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = -0.525; p = .002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized ß coefficient [ß]: .11; 95% confidence interval [CI]: 0.06-0.16; p < .001) and CSF fractalkine level (ß: -.62; 95% CI: -1.10 to -0.15; p = .012) were independent predictors of CPSP severity 6 months after TKA surgery. CONCLUSIONS: We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP.

Treatment of severe tricuspid regurgitation induced by permanent pacemaker lead: Transcatheter tricuspid valve replacement with the guidance of 3-dimensional printing.

Background: Lead-induced tricuspid regurgitation is one of the complications after permanent pacemaker implantation (PPI) and refers to tricuspid regurgitation (TR) caused by the lead in the right ventricle (RV). Objectives: To study the clinical characteristics of severe TR after PPI and the effect of transcatheter tricuspid valve replacement (TTVR) with the guidance of 3-dimensional (3D) printing. Methods: This study was a single-center, descriptive study. Six patients with severe TR after PPI were enrolled in Xijing Hospital from January 2020 to May 2020. Before TTVR, the 3D printed tricuspid valve (TV) model was used for evaluation in the bench test. LuX-Valve was implanted under the guidance of TEE and x-ray fluoroscopy, and all patients underwent transatrial access. Six patients' data were collected at baseline, before discharge, and 6 months, 1 year and 2 years after TTVR. Results: The LuX-Valve was successfully implanted in 6 patients, TR was significantly reduced to ≤2+, and no deaths or cardiopulmonary bypass occurred during procedures. Three cases were caused by TV expansion: Patient #4 had TR caused by lead adhesion to TV, Patient #2 had TR caused by lead winding, and Patient #6 had TR caused by lead impingement on TV. During the 2-year follow-up, TTE revealed that 5 patients had no/trace regurgitation, and one patient (Patient #5) had mild regurgitation. All 6 patients (100.0%) reached primary endpoints. Conclusion: TTVR guided by 3D printing is safe and effective in the treatment of severe TR associated with permanent pacemaker lead, providing prospects and possibilities for the precise treatment of TV-related diseases.Clinical Trial Registration: ClinicalTrials.gov Protocol Registration System (NCT02917980).

Effect of Defecation Delay in Patients After Tricuspid Valve Replacement: A Retrospective Study.

BACKGROUND: Defecation delay is a common symptom in patients after tricuspid valve replacement (TVR). Previous studies have demonstrated that defecation delay was associated with worse clinical outcomes of critically ill patients. Our study aimed to investigate the incidence and risk factors of defecation delay in patients after TVR and its adverse clinical outcomes. METHODS: A retrospective study was conducted in 206 patients undergoing TVR under cardiopulmonary bypass from May 2005 to July 2021. According to the first postoperative defecation time after surgery, patients were divided into the delayed group (>3 days) and control group (≤3 days). Baseline characteristics and preoperative, intraoperative, and postoperative data were collected to investigate the clinical outcomes of defecation delay. RESULTS: Among the 206 patients, 51.9% (107/206) cases were classified into the defecation delay group. Univariate analysis showed that age (P = 0.043), preoperative platelets (PLT) (P < 0.001), cardiopulmonary bypass (CPB) time (P = 0.013), minimum rectal temperature (P = 0.042), and the use of prokinetic drugs (P = 0.015) were significantly different in the two groups. In addition, the perioperative adverse events in the defecation delay group were significantly higher than that of the control group. Logistic regression analysis indicated that the mortality of patients was associated with postoperative renal dysfunction (P = 0.047) and postoperative respiratory failure (P = 0.004) but was not associated with defecation delay (P > 0.05). CONCLUSION: Patients with defecation delay after TVR were more likely to appear adverse events, however, defecation delay was not associated with mortality after TVR.

Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision.

Purpose: The involvement of hypoxic response mechanisms in local functional impairments in surgical wounds is unclear. In the present study, we characterized tissue hypoxia in surgical wounds and investigated the role of pharmacological ischemic conditioning (PIC) using roxadustat, an oral prolyl hydroxylase domain enzyme inhibitor, in postoperative local functional impairments in a murine model of deep hind paw incision. Methods: Male BALB/cAJcl mice aged 9-13 weeks were used in all experiments. Plantar skins of mice that underwent surgical incision were subjected to immunohistochemistry to localise tissue hypoxia. Pain-like behaviours and sudomotor function were compared between mice treated with 6-week perioperative PIC and control mice. The effects of PIC were examined in vitro by immunocytochemistry using sympathetically differentiated PC12 cells and in vivo by immunohistochemistry using plantar skins collected on postoperative day 21. Results: Prominent tissue hypoxia was detected within axons in the nerve bundles underneath surgical wounds. Six-week perioperative PIC using roxadustat failed to ease spontaneous pain-like behaviors; however, it mitigated local sudomotor impairment postoperatively. Upregulation of sympathetic innervation to the eccrine glands was observed in the PIC-treated skins collected on postoperative day 21, in accordance with the in vitro study wherein roxadustat promoted neurite growth of sympathetically differentiated PC12 cells. Conclusion: This study suggests that tissue hypoxia is involved in the pathogenesis of local sudomotor dysfunction associated with surgical trauma. Targeting the hypoxic response mechanisms with PIC may be of therapeutic potential in postsurgical local sympathetic impairments that can be present in complex regional pain syndrome.

Impact of transcatheter tricuspid valve replacement for tricuspid regurgitation on hepatic, cardiac, and venous structure.

BACKGROUND: Patients with long-term tricuspid regurgitation (TR) are mostly accompanied by hepatic, cardiac, and venous remodeling. Transcatheter tricuspid valve replacement (TTVR) device has emerged as a promising alternative to open-heart surgery for TR patients. No study has assessed the impact of TTVR on hepatic, cardiac, and venous remodeling. METHODS: Twenty-two patients with TR enrolled in this study underwent TTVR between October 2020 and January 2021. Liver, heart, and veins were reconstructed by three-dimensional computed tomography reconstruction software at baseline and 6 months follow-up. RESULTS: Twenty-two patients were enrolled in this study. The mean age was 64.8 ± 8.2 years, and all patients had severe or greater TR with multiple comorbidities. The left hepatic lobe volume decreased from 518.8 ± 171.9 ml to 470.4 ± 179.6 ml at 6 months during follow-up (p = 0.049). Evidence of a decrease in three hepatic veins parameters and splenic vein parameters was noted from baseline to 6 months. And a significant decrease in right atrial volume (317.5 ml [interquartile range: 216.1 to 497.3 ml] vs. 266.7 ml [interquartile range: 178.7 to 480.7 ml]; p = 0.003) were observed in the study. CONCLUSIONS: Six-month outcomes show that TR elimination by LuX-Valve is associated with the reverse remodeling of liver, heart, and veins. Accordingly, LuX-Valve is a promising alternative for patients presenting with severe TR.

Transjugular Transcatheter Tricuspid Valve Implantation of LuX-Valve Bioprosthesis in a Preclinical Model.

The purpose of this preclinical study in a sheep model was to confirm the feasibility and safety of the LuX-Valve transjugular tricuspid valve (TV) replacement apparatus and to optimize the implantation procedure before beginning first-in-man study. The LuX-Valve was implanted in a sheep model (n = 8) via transjugular approach. Six of eight sheep underwent successful implantation procedure on beating heart. The first two sheep died during the prostheses deployment. In the remaining 6 sheep that survived, postoperative echocardiography results showed there was no paravalvular leakage (PVL) and central tricuspid regurgitation in 5 animals, whereas 1 animal had mild PVL. The mean transvalvular gradient was 1.1 ± 0.9 mm Hg at the 4-week follow-up. No right ventricular outflow tract (RVOT) obstruction, device malposition, pericardial effusion, coronary artery compression, or arrhythmias were observed. This technology may be a promising alternative for TR patients who are at high risk for open-heart surgery. Transjugular tricuspid valved-stent implantation. a Transjugular tricuspid valve replacement in a sheep model. b and c Valved stent. d, e, and f Schematic depiction of the implantation procedure.

Pulmonary and tricuspid regurgitation after Tetralogy of Fallot repair: A case report.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common congenital heart defects, and surgery is the primary treatment. There are no precise guidelines on the treatment protocol for tricuspid regurgitation (TR) as a common complication of TOF repair. The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine. Here, we report the first case of sequential treatment of pulmonary and TR using interventional therapy. CASE SUMMARY: We present the case of a 52-year-old female patient, who had a history of TOF repair at a young age. A few years later, the patient presented with pulmonary and tricuspid regurgitation. The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation. Preoperative testing revealed that the patient's disease had advanced to an intermediate to advanced stage and that her general health was precarious. Because open-heart surgery was not an option for the patient, transcatheter tricuspid valve replacement was suggested. This procedure was successful, and the patient recovered fully without any adverse effects. This case report may serve as a useful resource for planning future treatments. CONCLUSION: Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair. The interventional strategy could be an alternative for patients with poor general health.

4-Year Follow-Up after Transatrial Transcatheter Tricuspid Valve Replacement with the LuX-Valve.

Tricuspid regurgitation (TR) has become one of the most common valve diseases. Patients with severe TR are often at high surgical mortality risk. Transcatheter tricuspid valve interventions have emerged as a promising alternative to open-heart surgery. The LuX-Valve is a novel radial force-independent transcatheter tricuspid valve replacement system. We presented here the first patient treated for symptomatic TR using the LuX-Valve replacement system in September 2018. Four-year follow-up outcomes suggested that the bioprosthesis was in normal function, with stable hemodynamics (mean transtricuspid gradient 2.55 mmHg) and the patient's clinical symptoms were significantly improved; thus indicating that it is a safe, effective, and satisfactory case of the LuX-Valve application in treating a patient with severe TR.

Transapical Transcatheter Aortic Valve Implantation for Aortic Regurgitation in Takayasu Arteritis.

Transcatheter aortic valve implantation (TAVI) has become a popular treatment for surgical high-risk patients with severe aortic stenosis (AS). Recently, we have applied TAVI to the treatment of aortic regurgitation (AR). Compared with conventional surgical procedures, TAVI is less invasive and considered a useful option for these high-risk patients. In this study, we reported a patient who underwent transapical TAVI. The patient was a 52-year-old female with Takayasu arteritis (TA) for 25 years, as well as with severe aortic regurgitation, porcelain aortas, and heart failure. Transapical TAVI successfully was accomplished without neurological complications, and heart failure immediately improved postoperatively.

Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus.

This study explored the correlation between peripheral blood CD3＋, CD3＋/CD4＋, CD3+/CD8+, CD4＋/CD8＋, CD3-/CD16+ CD56+, and CD3-CD19+ and disease activity of different subtypes of systemic lupus erythematosus (SLE). The percentages of CD3+, CD3+/CD4+, CD3+/CD8+, CD4+/CD8+, CD3-/CD16+ CD56+, and CD3-CD19+ in the peripheral blood of patients (n = 80) classified into lupus nephritis, blood involvement, and joint involvement and SLE in different active stages were detected by flow cytometry. Their correlations with baseline clinical experimental indicators of SLE patients' SLE disease activity index score (SLEDAI) and complement C3 were analyzed. The results showed that CD3+, CD3+/CD4+, and CD3+/CD8+ at baseline level were negatively correlated with SLEDAI scores. These were positively correlated with C3. In conclusion, T-lymphocyte subpopulations are closely related to SLE activity and can be used as reference indicators to evaluate the SLE activity.

Objective and Quantitative Evaluation of Spontaneous Pain-Like Behaviors Using Dynamic Weight-Bearing System in Mouse Models of Postsurgical Pain.

Background: The paucity of objective and reliable measurements of pain-like behaviors has impeded the translatability of mouse models of postsurgical pain. The advanced dynamic weight-bearing (DWB) system enables evaluation of spontaneous pain-like behaviors in pain models. This study investigated the suitability and efficiency of the DWB system for assessing spontaneous pain-like behaviors and analgesic therapies in murine models of postsurgical pain. Methods: Male adult C57BL/6JJcl mice were subjected to multiple surgical pain models with distinct levels of invasiveness, including a superficial incisional pain model involving only hind paw skin incision, deep incisional pain model that also involved incision and elevation of the underlying hind paw muscles, and orthopedic pain model involving tibial bone fracture and fixation with a pin (fracture and pinning [F/P] model). Spontaneous pain-like behaviors post-surgery were evaluated using weight distribution, pawprint area of the operated paw in the DWB system, and guarding pain score. Mechanical hypersensitivity was assessed using the von Frey test. The therapeutic effects of analgesics (diclofenac and buprenorphine for the deep incision model and diclofenac for the F/P model) were evaluated using the DWB system and von Frey test. Results: The von Frey test demonstrated contradictory results between superficial and deep incisional pain models. The DWB system captured weight distribution changes in the operated hind paw, in accordance with the invasiveness and time course of wound healing in these surgical pain models. The reduction in weight-bearing on the operated paw correlated with guarding score, degree of paw swelling, and local expression of inflammatory mediators. DWB enabled accurate evaluation of the pharmacological effects of analgesics for detecting attenuation of surgery-induced weight-bearing changes in these models. Conclusion: The DWB system serves as an objective and reliable method for quantifying pain-like behaviors and evaluating the therapeutic effects of analgesics in mouse models of postsurgical pain models.