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Objective A sizeable proportion of patients with secondary mitral regurgitation (SMR) do not receive guideline-directed medical therapy (GDMT) for heart failure (HF). We investigated the association between the use of GDMT and mortality in patients with SMR who underwent transcatheter edge-to-edge repair (TEER). Methods We retrospectively analysed patients with SMR and a left ventricular ejection fraction of <50% who underwent TEER at three centres. According to current HF guidelines, GDMT was defined as triple therapy consisting of beta-blockers, renin-angiotensin system (RAS) inhibitors and mineralocorticoid receptor antagonists (MRAs). Patients were divided into two groups: GDMT and non-GDMT groups. We calculated the propensity scores and carried out inverse probability of treatment weighting (IPTW) analyses to compare 2-year mortality between the two groups. Results Of 463 patients, 228 (49.2%) were treated with GDMT upon discharge. IPTW-adjusted Kaplan-Meier curve showed patients with GDMT had a lower incidence of mortality than those without GDMT (19.8% vs 31.1%, p=0.011). In IPTW-adjusted Cox proportional hazards analysis, GDMT was associated with a reduced risk of 2-year mortality (HR: 0.58; 95% CI: 0.35 to 0.95; p=0.030), which was consistent among clinical subgroups. Moreover, patients with GDMT had a higher rate of left ventricular reverse remodelling at 1 year after TEER than those without GDMT. Conclusion GDMT, defined as triple therapy consisting of beta-blockers, RAS inhibitors and MRAs, was associated with a reduced risk of 2-year mortality after TEER for SMR. Optimisation of medical therapy is crucial to improve clinical outcomes in patients undergoing TEER for SMR.

Background: In terms of pathophysiology, tricuspid regurgitation (TR) and right ventricular (RV) function are linked to each other. Aims: This study sought to evaluate RV-pulmonary artery (PA) coupling and its impact on clinical out-comes of TR in patients undergoing mitral transcatheter edge-to-edge repair (TEER). Methods: We calculated RV-PA coupling ratios in patients undergoing mitral TEER from August 2010 to March 2019 by dividing the tricuspid annular plane systolic excursion (TAPSE) by the echocardiographic estimated PA systolic pressure (PASP). TR was graded as none/trace, mild, moderate, or severe. The pri-mary outcome was all-cause mortality or rehospitalisation within 12 months. Results: Among 744 patients analysed, severe TR was documented in 22.3% of patients and the mean TAPSE/PASP was 0.43 +/- 0.25. Technical success of TEER was achieved in 97.2% of participants. Severe TR vs TR <= moderate (adjusted HR 1.92, 95% CI: 1.39-2.66) and TAPSE/PASP (adjusted HR 0.45, 95% CI: 0.22-0.93) were associated with the outcome. Patients were divided according to the TAPSE/PASP ter -tile. Compared to patients with TR <= moderate, patients with severe TR had a higher event rate (TAPSE/ PASP <0.30: 32.9% vs 45.1%; 0.30 <= TAPSE/PASP <0.44: 27.8% vs 41.8%; TAPSE/PASP <0.44: 16.0% vs 40.4%), whereas the prognostic significance of TR was attenuated in patients with reduced TAPSE/PASP (i.e., RV-PA uncoupling; interaction term p=0.03). The trends were consistent in the multivariable regres-sion models, spline curves, and sensitivity analysis using post-interventional parameters. Conclusions: RV-PA coupling affects the outcome correlation of TR in patients undergoing mitral TEER. The prognostic impact of TR is attenuated in patients with RV-PA uncoupling.

Background: In patients with severe mitral regurgitation (MR) who are scheduled for transcatheter mitral valve repair (TMVR), risk stratification is predominantly based on surgical risk scores. Aims: We sought to characterise and define stages of right heart remodelling in patients undergoing TMVR and evaluate the impact of this staging classification on survival. Methods: According to echocardiographic parameters, 929 patients undergoing MitraClip treatment were classified into three stages: severe MR without right heart damage (stage 0), with moderate-to-severe tricuspid regurgitation (TR) (stage 1), with right ventricular dysfunction defined as a reduced fractional area change <35% and a tricuspid annular plane systolic excursion <17 mm, or with increased right atrial area >25 cm2 and/or indexed right ventricular volume >30 ml/m2 (stage 2). We compared clinical outcomes and performed a multivariate analysis to evaluate the predictive value of the extent of cardiac damage. Results: Rates of one-year all-cause mortality increased with more advanced stages of right heart remodelling (stage 0: 8% vs stage 1: 9.7% vs stage 2: 18.1%; p<0.001). In the multivariate analysis, advanced cardiac damage was an independent predictor of one-year all-cause mortality (stage 2: p=0.007). Conclusions: A simple staging classification objectively characterises the extent of right heart remodelling caused by MR and allows risk prediction in patients undergoing a MitraClip procedure.

Secondary mitral regurgitation is common in patients with heart failure and associated with adverse outcome. Treatment was traditionally restricted to general heart failure therapy due to high surgical risk. Development of catheter-based techniques now offers treatment with acceptable risk. Albeit trial evidence is still limited, current European guidelines up-graded the recommendation of transcatheter therapies for patients with increased surgical risk and high probability of treatment response. However, several uncertainties remain with respect to the role of surgical treatment and patient selection for transcatheter therapies. In this review we summarize current status of treatment of secondary mitral regurgitation and show strategies of university networks with the aim to provide further evidence in support of the treatment.

BackgroundTranscatheter tricuspid valve repair (TTVr) is routinely performed under general anesthesia (GA). This study aimed to investigate whether TTVr procedures can be performed effectively and safely without GA but using deep sedation (DS). MethodsWe performed a retrospective analysis of 104 patients from three centers who underwent TTVr between 2020 and 2021. The primary performance endpoints were technical success and severity of TR assessed at the time of discharge. The safety outcome was a composite of in-hospital complications, including occurrence of death, conversion to surgery, major adverse cardiac and cerebrovascular events, major vascular complications, or occurrence of pneumonia. ResultsSixty-four procedures were performed in GA and 40 procedures were performed in DS. The groups did not differ in age, EuroScore II, TR severity, ventricular function, or hemodynamic parameters. Technical success was achieved in 92.5% of the patients in the DS group and in 93.6% of the patients in the GA group (p = 0.805). In none of the patients intraprocedural conversion from DS to GA was required. There was no difference in total duration of the procedure, and number of devices implanted. The degree of TR was <= 2+ in 77.5% of the patients in the DS group and in 74.2% of the patients in the GA group (p = 0.705). The composite safety endpoint did not differ between the groups (2.5 vs. 6.3%, p = 0.384). The total duration of hospital stay was shorter in patients who underwent TTVr in DS compared to those who underwent TTVr in GA (6 [5, 9] days vs. 8 [6, 11] days; p = 0.011). ConclusionPerforming TTVr in DS was effective with similar procedural results, and was safe with similar low complication rates compared to GA.

The prevalence of left ventricular (LV) thrombus formation following percutaneous mitral valve edge-to-edge repair (TMVR) with the MitraClip system is unclear. Decreased total stroke volume and perfusion of the LV apex after mitral valve repair may facilitate thrombus formation especially in the context of reduced LV function. LV thrombus may cause disabling stroke or other thromboembolic events in this elderly and multimorbid patient cohort. Analyses of the prevalence of and risk factors for left ventricular thrombus formation in patients treated with the MitraClip system due to severe mitral valve regurgitation. All discharge and follow-up transthoracic echocardiographic examinations up to 6 months of 453 consecutive patients treated with the MitraClip system were screened for the presence of LV thrombus. Prevalence of LV thrombus formation was 1.1% (5/453). Importantly, LV thrombi were exclusively found in patients with severely depressed left ventricular systolic function (LV-EF < 30%), comprising a prevalence of 4.4% in this subgroup (5/113). Importantly, two of these patients were under active DOAC therapy with Rivaroxaban and Apixaban, respectively. Apart from LV-EF, we did not identify other factors that might have facilitated LV thrombus formation. LV thrombus formation following percutaneous mitral valve repair occurred exclusively in patients with severely depressed LV-EF. As two patients developed LV thrombus despite of DOAC therapy, anticoagulation with a Vitamin K antagonist should be considered in patients with an indication for oral anticoagulation following TMVR.

Secondary mitral and tricuspid regurgitation are common in heart failure caused by geometrical or functional alterations of the ventricles and/or atria despite structurally normal valve apparatus. By inducing volume overload of the ventricles, mitral or tricuspid regurgitation substantially contributes to heart failure symptoms and progression and thus critically impacts prognosis. Due to high surgical risk, therapeutic options were traditionally limited to general heart failure therapy. Yet, the development of transcatheter techniques allows treatment of secondary AV valve regurgitation with acceptable risk and based on recent trial results has become a cornerstone of contemporary heart failure therapy. Herein, we will give an overview of interventional strategies for the treatment of secondary mitral and tricuspid regurgitation and discuss their current role in clinical practice.

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to cancer itself or cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. The management of acute coronary syndromes and acute pericardial diseases in cancer patients was covered in part 1 of a clinical consensus document. This second part focusses on acute heart failure, acute myocardial diseases, venous thromboembolic diseases and acute arrhythmias.

Aims To investigate the role of left atrial volume index (LAVi) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (TEER). Methods and results Outcomes were evaluated in SMR patients of a European multicentre registry according to baseline LAVi. Main analysis was performed for all-cause mortality; residual mitral regurgitation (MR) and New York Heart Association (NYHA) class improvement were analysed for patients available. A total of 1074 patients were included with a median LAVi (interquartile range) of 58 ml/m(2) (46-73). Postprocedural reduction of MR grade to <= 2+ was similar across LAVi quintiles, ranging 91%-96% (p = 0.26). Symptomatic benefit (>= 1 NYHA class improvement) also did not differ by LAVi quintiles (61%-68% of patients) (p = 0.66). The risk of mortality increased by 23%-42% in the four upper quintiles compared to the bottom quintile (LAVi <42 ml/m(2)). The hazard ratio (HR) of mortality was 1.35 (95% confidence interval [CI] 1.02-1.78, p = 0.035) associated with a LAVi >42 ml/m(2), which was attenuated after multivariable adjustment (HR 1.18, 95% CI 0.83-1.67, p = 0.36). A significant interaction was found for MR severity and pulmonary hypertension, with an increased risk of death associated with enlarged LAVi in patients with inframedian effective regurgitant orifice area (HR 1.99, 95% CI 1.06-3.74, p = 0.032) and in patients with systolic pulmonary pressure <= 50 mmHg (HR 1.67, 95% CI 1.02-2.75, p = 0.042) in multivariable analysis. Conclusion Procedural success and symptomatic benefit were high throughout the whole range of LAVi. The prognostic impact of left atrial enlargement was relevant in patients with less severe SMR and without pulmonary hypertension, reinforcing the need to identify patients in the early course of backward congestion to achieve good long-term outcome after TEER.

Background Severe tricuspid regurgitation (TR) is independently associated with increased morbidity and mortality. Percutaneous transcatheter approaches may offer an alternative for patients not amenable to surgery. Methods TriCLASP is a prospective, single-arm, multicenter European post-market clinical follow-up study (NCT04614402) to evaluate the safety and performance of the PASCAL system (Edwards Lifesciences) in patients with severe or greater TR. At 30 days, a composite of major adverse events (MAEs) adjudicated by a clinical events committee, echocardiographic parameters adjudicated by core laboratory, and clinical, functional, and quality-of-life measures were evaluated. Results Mean age of the 74 enrolled patients was 80.3 years, with 58.1% female, 90.5% systemic hypertension, and 77.0% in New York Heart Association (NYHA) class III/IV. Mean Society for Thoracic Surgeons score (MV repair) was 9.0%. TR severity was significantly reduced at discharge (p < 0.001) and sustained at 30 days (p < 0.001), and 90.0% of patients achieved <= moderate TR. The composite MAE rate at 30 days was 3.0%, including 4 events in 2 patients: cardiovascular mortality 1.5%, stroke 1.5%, renal complications requiring unplanned dialysis or renal replacement therapy 1.5%, and severe bleeding 1.5%. There were no nonelective tricuspid valve reinterventions, major access site and vascular complications, major cardiac structural complications, or device embolizations. NYHA class I/II was achieved in 55.8%, 6-minute walk distance improved by 38.2 m (p < 0.001), and Kansas City cardiomyopathy questionnaire scores improved by 13.4 points (p < 0.001). Conclusion Experience with the PASCAL transcatheter valve repair system in a European post-market setting confirms favorable safety and effectiveness at 30 days. TR significantly reduced, and clinical, functional, and quality-of-life outcomes significantly improved. This study is ongoing. Clinical Trial Registration: The study is ongoing and re

OBJECTIVES This study aimed to improve echocardiographic assessment of pulmonary hypertension (PH) in patients presenting with severe tricuspid regurgitation (TR). BACKGROUND Echocardiographic assessment of PH in patients with severe TR carries several pitfalls for underestimation, hence concealing the true severity of PH in very sick patients in particular, and ultimately obscuring the impact of PH on survival after transcatheter tricuspid valve intervention (TTVI). METHODS All patients in this study underwent TTVI for severe TR between 2016 and 2020. To predict the mean pulmonary artery pressure (mPAP) solely based on echocardiographic parameters, we trained an extreme gradient boosting (XGB) algorithm. The derivation cohort was constituted by 116 out of 162 patients with both echocardiography and right heart catheterization data, preprocedurally obtained, from a bicentric registry. Moreover, 142 patients from an independent institution served for external validation. RESULTS Systolic pulmonary artery pressure was consistently underestimated by echocardiography in comparison to right heart catheterization (40.3 +/- 15.9 mm Hg vs 44.1 +/- 12.9 mm Hg; P = 0.0066), and the assessment was most discrepant among patients with severe defects of the tricuspid valve and impaired right ventricular systolic function. Using 9 echocardiographic parameters as input variables, an XGB algorithm could reliably predict mPAP levels (R = 0.96, P < 2.2 x 10(-16)). Moreover, patients with elevations in predicted mPAP levels >= 29.9 mm Hg showed significantly reduced 2-year survival after TTVI (58.3% [95% CI: 41.7%-81.6%] vs 78.8% [95% CI: 68.7%-90.5%]; P = 0.026). Importantly, the poor prognosis associated with elevation in predicted mPAP levels was externally confirmed (HR for 2-year mortality: 2.9 [95% CI: 1.5-5.7]; P = 0.002). CONCLUSIONS PH in patients with severe TR can be reliably assessed based on echocardiographic parameters in conjunction with an XGB algorithm, and elevations

Background: Recurrent mitral regurgitation (MR) following MitraClip has not been thoroughly investigated. We aimed to examine the predictive factors, morphology, and long-term outcome of recurrent MR after MitraClip. Methods: We assessed data from the Heart Failure Network Rhineland registry from August 2010 to October 2018. Competing risk analyses were performed using the Fine and Gray model to assess the risk of recurrent MR. Results: Among 685 MitraClip patients with a reduction in MR to <= 2+, 61 patients developed recurrent MR within the first 12 months. Flail leaflet (hazard ratio, 3.68; P=0.002) and residual MR (MR grade 2+ versus <= 1+: hazard ratio, 2.56; P=0.03) were the predictors of recurrent MR in primary MR patients, while left atrial volume (per 10 mL increase: hazard ratio, 1.11; P<0.001) and residual MR (hazard ratio, 2.45; P=0.01) were independently associated with recurrent MR in secondary MR patients. In primary MR patients, loss of leaflet insertion or leaflet tear were the predominant morphologies with recurrent MR. In secondary MR patients, more than half of the patients with recurrent MR did not show any disorder of the clip or leaflets. Patients with recurrent MR were more likely to experience unplanned heart failure hospitalization or heart failure symptom with New York Heart Association scale III/IV (54.1% versus 37.8%; P=0.018) and undergo a repeat mitral valve intervention (9.8% versus 2.2%; P=0.005) during the follow-up. In the landmark survival analysis, patients with recurrent MR tended to have lower long-term survival (58.7% versus 83.9%; P=0.08) than patients without recurrent MR. Conclusions: Flail leaflet and residual MR were the predictors of recurrent MR in primary MR patients, while a larger left atrial volume and residual MR were associated with recurrent MR in secondary MR patients, which may be associated with long-term clinical outcomes of patients after MitraClip.