Transcatheter Treatment of Mitral Valve Regurgitation in the Setting of Concomitant Coronary or Multivalvular Heart Disease: A Focused Review.

Treatment for mixed valve disease has historically been limited, often surgery being the only option. With the recent advancement of transcatheter therapies, percutaneous approaches are quickly becoming viable therapeutic considerations in inoperable or high-risk patients, also offering the option for a staged or same-session treatment. Guidelines are primarily focused on single-valve disease. However, patients often present with multiple pathologies. This review summarizes the data and literature on transcatheter treatment of patients with mitral regurgitation who concomitantly have aortic stenosis or regurgitation, tricuspid regurgitation, or ischemic cardiomyopathy. Pathophysiology, hemodynamics, available therapies as well as order and timing of interventions are discussed.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

Tricuspid Regurgitation and Clinical Outcomes in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Tricuspid regurgitation (TR) is common and is associated with poor outcomes in patients with heart failure (HF). However, data with adjudicated events from fully characterized patients with heart failure with reduced ejection fraction (HFrEF) are lacking. OBJECTIVES: This study sought to explore the association between mild or moderate/severe TR and clinical outcomes of patients with HFrEF. METHODS: GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) was a double-blind, placebo-controlled randomized trial comparing omecamtiv mecarbil vs placebo in patients with symptomatic HFrEF. RESULTS: Among the 8,232 patients analyzed in the GALACTIC-HF trial, 8,180 (99%) had data regarding baseline TR (none: n = 6,476 [79%], mild: n = 919 [11%], and moderate/severe: n = 785 [10%]). The primary composite outcome of a first HF event or cardiovascular death occurred in 2,368 (36.6%) patients with no TR, 353 (38.4%) patients with mild TR, and 389 (49.6%) patients with moderate/severe TR. Moderate/severe TR was independently associated with a higher relative risk of the primary composite outcome compared with either no TR (adjusted HR: 1.12 [95% CI: 1.01-1.26]; P = 0.046) or no/mild TR (adjusted HR: 1.14 [95% CI: 1.02-1.27]; P = 0.025) driven predominantly by HF events. The association between moderate/severe TR and clinical outcomes was more pronounced in outpatients with worse renal function, higher left ventricular ejection fraction, and lower N-terminal pro-B-type natriuretic peptide and bilirubin levels. The beneficial treatment effect of omecamtiv mecarbil vs placebo on clinical outcomes was not modified by TR. CONCLUSIONS: In symptomatic patients with HFrEF, baseline moderate/severe TR was independently associated with cardiovascular death or HF events driven predominantly by HF events. The beneficial treatment effect of omecamtiv mecarbil on the primary outcome was not modified by TR.

Management of penetrating cardiac injury and tricuspid regurgitation with extracorporeal-membrane oxygenation (ECMO): a case report.

BACKGROUND: Gunshot wounds (GSW) to the heart are lethal, and most patients die before they arrive to the hospital. Survival decreases with number of cardiac chambers involved. We report a case of a 17-year-old male who survived a GSW injury involving two cardiac chambers with acute severe tricuspid regurgitation (TR) who subsequently developed cardiogenic shock requiring extracorporeal membrane oxygenation (ECMO) support. CASE PRESENTATION: A 17-year-old male sustained a single gunshot wound to the left chest, resulting in pericardial tamponade and right hemothorax. Emergency sternotomy revealed injury to the right ventricle and inferior cavoatrial junction with the adjacent pericardium contributing to a right hemothorax. The cardiac injuries were repaired primarily. Tricuspid regurgitation was confirmed immediately postoperatively. Five days after presentation, the patient developed cardiogenic shock secondary to TR requiring emergent stabilization with ECMO. He subsequently underwent successful tricuspid valve replacement. CONCLUSIONS: This is the first report to our knowledge of successful ECMO support of severe TR due to gunshot injury to the heart.

Anaesthetic management of a patient with severe pulmonary hypertension, moderate tricuspid regurgitation and moderate right ventricular dysfunction presenting for a dilation and curettage.

A primigravida woman in her 30s with severe pulmonary hypertension, tricuspid regurgitation and depressed right ventricular function presented for therapeutic termination of pregnancy at 7 weeks gestation after referral and multidisciplinary recommendation. A slowly titrated lumbar epidural was chosen for the primary anaesthetic. Under standard American Society of Anesthesiologists (ASA) monitoring, invasive blood pressure monitoring and continuous transthoracic echocardiography, the patient's right ventricular systolic function was monitored throughout the case using qualitative and quantitative metrics and was notable for a right ventricular systolic pressure of 102.4 mm Hg. Milrinone, started prior to epidural titration, was used for inotropic support. Vasopressin was used in conjunction to sustain systemic vascular resistance while having little effect on the pulmonary vascular resistance. The patient experienced no complications or exacerbation of her pulmonary hypertension and was discharged home the following day.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

BACKGROUND: There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. METHODS AND RESULTS: A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects of warfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. CONCLUSIONS: In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Severe tricuspid regurgitation with chordae tendinae rupture in CABG surgery.

A 58-year-old male patient was admitted with chest pain and was diagnosed with coronary heart disease. He was scheduled for coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Intraoperative real-time transesophageal echocardiography (TEE) showed that the tricuspid valves were well-aligned and subtle regurgitation. Real-time TEE after separation from CPB showed severe tricuspid regurgitation and prolapsed chordae tendineae. The tricuspid chordae tendineae rupture due to a right atrial venous return cannula. The use of negative pressure to improve venous drainage during CPB may result in the tricuspid valve being adsorbed to the cannula, increasing the likelihood of injury to the tricuspid valve.

Impact of tricuspid regurgitation severity on mortality in pulmonary hypertension patients: A comprehensive analysis.

BACKGROUND: Pulmonary hypertension (PH) presents as a complex cardiovascular condition with a highly variable prognosis. Secondary tricuspid regurgitation (TR), a frequent comorbidity in PH, has an uncertain impact on patient outcomes. This study investigates the relationship between the severity of TR and mortality in patients with PH. METHODS: A retrospective analysis of 110 PH patients who underwent right-heart catheterization was conducted. TR severity was categorized echocardiographically as mild, moderate, or severe. Both univariate and multivariate Cox regression analyses were used to assess predictors of mortality. RESULTS: The median age of the cohort was 60 years, predominantly female (65 %). Severe TR was present in 36 % of patients. Over a 20-month median follow-up, mortality was notably higher in patients with severe TR (30 %) compared to those with milder forms (15 %, p = 0.04). Multivariate analysis confirmed severe TR, WHO functional class III/IV, and right ventricular stroke work index as independent predictors of mortality. CONCLUSION: Severe TR significantly predicts increased mortality in PH patients, underscoring its importance in patient management. These findings advocate for early detection and comprehensive management of TR, integrating its assessment into routine PH care to potentially enhance patient outcomes.

Right ventricular remodeling and clinical outcomes following transcatheter tricuspid valve intervention.

AIMS: Characterize the impact of residual tricuspid regurgitation (TR) on right ventricle (RV) remodeling and clinical outcomes after transcatheter tricuspid valve intervention. METHODS: We performed a single-center retrospective analysis of transcatheter tricuspid valve repair (TTVr) or replacement (TTVR) patients. The primary outcomes were longitudinal tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulmonary artery systolic pressure (PASP), and RV dimensions (RVd). We used multivariable linear mixed models to evaluate association with replacement versus repair and degree of TR reduction with changes in these echo measures over time. Multivariable Cox regression was used to identify associations between changes in these echo measures and a composite clinical outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention. RESULTS: We included a total of 61 patients; mean age was 77.5 ± 11.7 and 62% were female. TTVR was performed in 25 (41%) and TTVr in 36 (59%). Initially, 72% (n = 44) had ≤ severe TR and 28% (n = 17) had massive or torrential TR. The median number of follow up echos was 2: time to 1st follow-up was 50 days (interquartile range [IQR]: 20, 91) and last follow-up was 147 (IQR: 90, 327). Median TR reduction was 1 (IQR: 0, 2) versus 4 (IQR: 3, 6) grades in TTVr versus TTVR (p < 0.0001). In linear mixed modeling, TTVR was associated with decline in TAPSE and PASP, and TR reduction was associated with decreased RVd. In multivariable Cox regression, greater RVd was associated with the clinical outcome (hazard ratio: 9.27, 95% confidence interval: 1.23-69.88, p = 0.03). CONCLUSION: Greater TR reduction is achieved by TTVR versus TTVr, which is in turn associated with RV reverse remodeling. RV dimension in follow-up is associated with increased risk of a composite outcome of death, heart failure hospitalization, or re-do tricuspid valve intervention.

A comparison between patients with various etiologies of cirrhosis and examination of cardiac risk factors limiting survival to liver transplantation.

BACKGROUND & AIMS: Objectives of this retrospective cohort study were to assess differences in patient survival between etiologies of cirrhosis while on the waitlist for liver transplantation (LT), and to identify cardiac risk factors that predict survival failure while on the waitlist for LT. METHODS: This single-center retrospective cohort design included adult patients who were listed for LT at a tertiary academic hospital with a high-volume liver transplant center. RESULTS: Of the 653 patients listed for LT during the study period, 507 (77.6%) survived to transplant and 146 (22.4%) died or clinically deteriorated prior to transplant. Cumulative incidence of death or clinical deterioration did not differ statistically between patient groups (log rank p = .11). In multivariate analysis, compared to patients with NAFLD, there were no significant differences between patients with alcoholic cirrhosis (HR .95, 95%, CI, .62-1.45), cryptogenic cirrhosis (HR 1.31, 95%, CI, .77-2.23), or hepatitis C cirrhosis (HR 1.12, 95%, CI, .66-1.90). However, higher MELD scores (HR = 1.52, 95% CI, 1.12-1.19), severe coronary artery disease (HR = 2.09 95% CI, 1.23-3.55), and tricuspid regurgitation (HR = 2.62, 95% CI, 1.31-5.26) were independently associated with increased risk for survival failure to LT. CONCLUSIONS: The presence of severe coronary artery disease and tricuspid regurgitation at the time of listing for transplant are associated with survival failure while on the LT waitlist across etiologies of liver disease. Diagnostic assessment of coronary and valvular disease should be considered in all patients undergoing evaluation for LT, such as cardiac catheterization and/or stress echocardiogram.

Contemporary Approach to Tricuspid Regurgitation: Knowns, Unknowns, and Future Challenges.

Severe tricuspid regurgitation (TR) worsens heart failure and is associated with impaired survival. In daily clinical practice, patients are referred late, and tricuspid valve interventions (surgical or transcatheter) are underutilised, which may lead to irreversible right ventricular damage and increases risk. This article addresses the appropriate timing and modality for an intervention (surgical or transcatheter), and its potential benefits on clinical outcomes. Ongoing randomised controlled trials will provide further insights into the efficacy of transcatheter valve interventions compared with medical treatment.

ECG patterns to predict pulmonary arterial hypertension in patients with severe tricuspid regurgitation.

INTRODUCTION: Echocardiographic evaluation of tricuspid regurgitation (TR) velocity is a key measure in screening for pulmonary hypertension. Based on its value and additional features of right ventricle overload patients are classified into low, intermediate or high probability of pulmonary hypertension which transfers into decisions of further invasive evaluation. However, in the presence of severe TR echocardiography underestimates pulmonary artery pressure and therefore pulmonary hypertension may be overlooked in some patients. Accordingly, in the present study we aimed to assess the role of electrocardiography in predicting the presence of pulmonary arterial hypertension (PAH) in patients with severe TR. RESULTS: We analysed 83 consecutive patients with severe TR who were diagnosed in our centre between February 2008 and 2021 and who underwent right heart catheterization. Of them 58 had PAH while 25 had isolated TR (iTR). We found that the following ECG criteria supported the diagnosis of PAH as opposed to the diagnosis of iTR: R:SV1 > 1.0, max RV1 or 2 + max S I or aVL -SV1 > 6 mm, SI/RI > 1 in I. For these parameters using ROC analysis we found that the optimal thresholds suggesting the presence of pulmonary hypertension were: R:SV1 > 1.5 (AUC = 0.74, p = 0.0004, sensitivity 57.1%,specificity of 85%), max RV1 or 2 + max S I or aVL - SV1 > 3 mm (AUC = 0.76, p < 0.0001, sensitivity 91.4%, specificity of 60%) and for SI:RI > 0.71 (AUC = 0.79, p < 0.0001, sensitivity 82.5%,specificity of 70.8%). Presence of atrial fibrillation predicted iTR with 76% sensitivity and 81% specificity. CONCLUSIONS: ECG analysis can improve the diagnostic process for patients with severe TR. The presence of atrial fibrillation facilitates the diagnosis of isolated tricuspid regurgitation (iTR), while increased values of R:SV1, R:SI, and increased max RV1 or 2 + max SI or aVL - SV1 favor the diagnosis of TR secondary to PAH.

Outcomes of tricuspid valve prostheses after heart transplantation: a systematic review.

Tricuspid regurgitation (TR) is the most common valvular pathology after heart transplantation (HTx) and endomyocardial biopsy (EMB) remains responsible for the majority of cases due to the high probability of structural valve damage. The aim of the present review was to describe the results of surgical management of severe tricuspid regurgitation through tricuspid valve replacement (TVR) after a previous HTx. A systematic review was conducted by searching Pubmed, ScienceDirect, SciELO, DOAJ, and Cochrane databases until June 2023 for publications reporting patients undergoing TVR surgery after a previous HTx. If no right heart valve surgery was undertaken, or a heterotopic heart transplant was performed, or if the concomitant procedure was performed during the transplant itself, the paper was excluded. Twenty articles met our inclusion criteria out of 1532 potentially eligible studies, with a total of 300 patients. Mean age was 55.1 ± 9.6 years, and 85.1% were male. The mean number of EMB per patient was 31.1 ± 5.5 with a mean time between HTx and TVR of 7.64 ± 3.31 years. Bioprostheses were used in 83.3% of cases and 75.0% of patients with a bioprosthesis were reported as alive at last follow-up. Tricuspid valve repair is a valuable option, but these patients will be susceptible to recurrent TR after EMB. TVR with a bioprosthesis may provide the optimal solution for this subset of patients, as EMB is not feasible with a mechanical valve.

Transjugular tricuspid valve-in-ring replacement using the novel system under three-dimensional printing guidance.

Recurrent tricuspid regurgitation after failed ring annuloplasty is associated with high mortality rates and unfavourable clinical outcomes. Transcatheter tricuspid valve-in-ring (TVIR) replacement offers an alternative to high-risk surgical reoperation, but challenges remain. We present a case of a 67-year-old male who underwent tricuspid annuloplasty 3 years ago and developed severe recurrent tricuspid regurgitation (regurgitation volume = 36 mL) 6 months ago. To avoid a high-risk thoracotomy, we finally performed TVIR replacement using the novel device, LuX-Valve Plus system, via the transjugular approach. Cardiovascular three-dimensional printing technology was utilized to investigate the distinct advantages offered by the new device in this specific intervention, as well as to simulate the procedure. Successful TVIR replacement resulted in significant symptomatic improvement. TVIR replacement with the LuX-Valve Plus system is feasible for failed annuloplasty ring cases. Patient-specific three-dimensional printed models enable personalized procedural planning, enhancing safety and precision.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

[Profuse Hemorage During Open Heart Surgery in a Patient Late After Liver Transplantation and Remission Stage Acquired Hemophilia].

A 72-year-old male presented with severe mitral regurgitation, moderate tricuspid regurgitation, and chronic atrial fibrillation. One month prior, he encountered difficulties with dialysis and was subsequently referred to our department for cardiac surgery. The patient's medical history includes living-donor liver transplantation for type C cirrhosis associated with acquired hemophilia A. The preoperative liver function was categorized as Child-Pugh grade B, with a model for end-stage liver disease( MELD) score of 23. His factor Ⅷ activity was close to the lower limit of the normal range. The patient underwent mitral valve replacement, tricuspid valve repair, and left atrial appendage closure. Initially, he experienced intractable bleeding, but hemostasis was easily achieved after administrating a factor Ⅷ preparation. Upon admission to the intensive care unit, his factor Ⅷ clotting activity was slightly below the normal range. Therefore, in cases where a patient with remission stage hemophilia A resulting in liver transplantation undergoes open heart surgery, it is crucial to have coagulation factor medication readily available, regardless of normal preoperative factor Ⅷ levels.

Machine learning facilitates the prediction of long-term mortality in patients with tricuspid regurgitation.

OBJECTIVE: Tricuspid regurgitation (TR) is a prevalent valve disease associated with significant morbidity and mortality. We aimed to apply machine learning (ML) to assess risk stratification in patients with ≥moderate TR. METHODS: Patients with ≥moderate TR on echocardiogram between January 2005 and December 2016 were retrospectively included. We used 70% of data to train ML-based survival models including 27 clinical and echocardiographic features to predict mortality over a 3-year period on an independent test set (30%). To account for differences in baseline comorbidities, prediction was performed in groups stratified by increasing Charlson Comorbidity Index (CCI). Permutation feature importance was calculated using the best-performing model separately in these groups. RESULTS: Of 13 312 patients, mean age 72 ± 13 years and 7406 (55%) women, 7409 (56%) had moderate, 2646 (20%) had moderate-severe and 3257 (24%) had severe TR. The overall performance for 1-year mortality by 3 ML models was good, c-statistic 0.74-0.75. Interestingly, performance varied between CCI groups, (c-statistic = 0.774 in lowest CCI group and 0.661 in highest CCI group). The performance decreased over 3-year follow-up (average c-index 0.78). Furthermore, the top 10 features contributing to these predictions varied slightly with the CCI group, the top features included heart rate, right ventricular systolic pressure, blood pressure, diuretic use and age. CONCLUSIONS: Machine learning of common clinical and echocardiographic features can evaluate mortality risk in patients with TR. Further refinement of models and validation in prospective studies are needed before incorporation into the clinical practice.

Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from the TriValve registry.

AIM: Functional or secondary tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs. VSTR) are lacking. The aim of this study was to assess characteristics and outcomes of patients with ASTR versus VSTR undergoing T-TEER. METHODS AND RESULTS: Patients with STR undergoing T-TEER were selected from the Transcatheter Tricuspid Valve Therapies (TriValve) registry. ASTR was defined by (i) left ventricular ejection fraction ≥50%, (ii) atrial fibrillation, and (iii) systolic pulmonary artery pressure <50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key endpoints included procedural success and survival at follow-up. A total of 298 patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs. 83% for ASTR vs. VSTR, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12-month follow-up, survival was significantly higher in the ASTR versus VSTR cohort (91% vs. 72%, log-rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75). CONCLUSIONS: In a real-world, multicentre registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-month follow-up, ASTR showed better survival than VSTR.