Comparison of transcatheter leaflet-approximation and direct annuloplasty in tricuspid regurgitation.

BACKGROUND: Transcatheter repair emerges as a treatment option in patients with tricuspid regurgitation (TR) and high surgical risk. AIMS: This study aimed to compare leaflet-based and annuloplasty-based transcatheter repair in patients with TR. METHODS: In a retrospective analysis consecutive patients undergoing either transcatheter edge-to-edge repair (TEER) or direct annuloplasty (AP) for relevant TR at 2 centers were compared with respect to baseline characteristics, procedural efficacy and safety (death, myocardial infarction, procedure or device-related cardiothoracic surgery, or stroke at 30 days). RESULTS: 161 patients (57% female, median age 79 [75-82] years) with comparable clinical baseline characteristics in the TEER (n = 87) and AP (n = 74) group were examined. Baseline TR grade was significantly less severe in the TEER compared to the AP group (torrential 9.2 vs. 31.1%, p = 0.001). Technical success and improvement of TR grades were not significantly different across groups. In analysis matched for baseline TR severity, reduction of TR grade to less than moderate was significantly more common in the AP group (47.8 vs. 26.1%, p = 0.031). Major or more severe bleeding occurred in 9.2% of TEER and 20.3% of AP patients (p = 0.049) without any fatal bleedings. Major adverse events (MAE) were similar across groups with four patients (4.7%) in the TEER group and five patients (6.9%) in the AP group (p = 0.733) and 6-month survival did not differ significantly. CONCLUSIONS: Differences observed between patients treated with TEER and AP provide first evidence for tailoring distinct transcatheter treatment techniques to individual patient characteristics.

Contemporary treatment of mitral valve disease with transcatheter mitral valve implantation.

BACKGROUND: Transcatheter mitral valve implantation (TMVI) with self-expanding (SAV) or balloon-expandable (BAV) valves are rising as promising treatment options for high-risk patients with symptomatic mitral valve (MVD) disease unsuitable for alternative treatment options. AIMS: The aim of this study was to examine the clinical, procedural and outcome parameters of patients undergoing SAV or BAV for MVD. METHODS: In this observational and single-center case series, fifteen consecutive patients treated with the Tendyne Mitral Valve System (SAV) and thirty-one patients treated with SAPIEN prosthesis (BAV) were included. RESULTS: The patients (aged 78 years [interquartile range (IQR): 65.5 to 83.1 years], 41% women, EuroSCORE II 10.3% [IQR: 5.5 to 17.0%] were similar regarding baseline characteristics, despite a higher rate of prior heart valve surgery and prevalence of MV stenosis in the SAV-group. At discharge, the SAV-group had a mean transvalvular gradient of 4.2 mmHg, whereas the BAV-group had a mean transvalvular gradient of 6.2 mmHg. None or trace paravalvular leakage (PVL) was assessed in 85% in SAV-group and 80% in the BAV-group. 320 day all-cause and cardiac mortality rates were comparable in both groups (SAV: 26.7% vs BAV: 20%, p = 0.60). Four deaths occurred early in the SAV-group until 32 days of follow-up. CONCLUSIONS: In high-risk patients with MVD, TMVI presents a promising treatment option with encouraging mid-term outcomes and good valve durability. TMVI either with BAV or SAV may be developed to an established treatment option.

Association of iron deficiency, anaemia, and functional outcomes in patients undergoing edge-to-edge mitral valve repair.

AIMS: Patients undergoing percutaneous mitral valve repair (PMVR) show a substantial heterogeneity of prognostic and symptomatic benefit. Iron deficiency and anaemia are associated with worse outcomes in heart failure patients. We investigated the impact of these comorbidities on functional and clinical outcome after PMVR. METHODS AND RESULTS: Iron deficiency and anaemia were prospectively assessed in 130 patients undergoing PMVR with MitraClip. Associations with functional outcomes at 6 weeks [6 min walking distance (6MWD), Short-Form-36 physical component score, and Minnesota Living with Heart Failure Questionnaire score, New York Heart Association class] and long-term clinical outcome were examined. Iron deficiency and anaemia were frequent with 52% and 50%, respectively. Patients with anaemia showed significant worse baseline functional measures, whereas patients with iron deficiency showed only a trend for lower baseline 6MWD. The benefit in functional outcomes after PMVR was notable and did not differ significantly by iron deficiency or anaemia status (range of median changes in 6MWD 35 to 45 m, physical component score 5.6 to 7.2, Minnesota Living with Heart Failure Questionnaire -8.0 to -10.5; improvement of ≥1 New York Heart Association class 69% to 80%). Anaemia was associated with higher risk for the combined endpoint of mortality and heart failure hospitalization (hazard ratio: 2.51; 95% confidence interval: 1.24-5.1; P = 0.01), whereas iron deficiency showed a trend towards more heart failure hospitalizations (hazard ratio: 2.94; 95% confidence interval: 0.94-9.03; P = 0.09). CONCLUSIONS: The prevalence of iron deficiency and anaemia is high in patients undergoing MitraClip. Clinical baseline status and long-term outcome were worse particularly in patients with anaemia. However, the functional benefit of PMVR was equal in patients with and without iron deficiency and anaemia.

Impact of device landing zone calcification patterns on paravalvular regurgitation after transcatheter aortic valve replacement with different next-generation devices.

OBJECTIVE: Residual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves. METHODS: 642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge. RESULTS: PVR was ≥moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p<0.001), and these differences remained after matching for total DLZ calcium volume. The amount of DLZ calcium was significantly related to the degree of PVR in patients treated with S3 (p=0.045), NEO (p=0.004) and ER (p<0.001), but not in Lotus patients (p=0.698). The incidence of PVR ≥moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR. CONCLUSIONS: The susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics.

Acute kidney injury following percutaneous edge-to-edge vs. minimally invasive surgical mitral valve repair: incidence, predictors and prognostic value.

AIMS: This study sought to determine the incidence and identify predictors of acute kidney injury (AKI) following percutaneous edge-to-edge mitral valve repair (PMVR) and compare the risk of AKI between PMVR and surgical mitral valve repair (SMVR). METHODS AND RESULTS: We performed a single-centre analysis of 378 patients receiving treatment for mitral regurgitation (196 consecutive patients undergoing PMVR and 182 patients undergoing SMVR). The incidence of AKI (any stage according to KDIGO) following PMVR was 17.9%. Intervention duration (OR 1.01, 95% CI: 1.00-1.02) and peripheral vascular disease (OR 7.69, 95% CI: 3.25-18.17) predicted AKI after PMVR. Patients suffering from AKI after PMVR demonstrated poorer survival (median followup 428 days). SMVR patients were significantly younger, had fewer comorbidities and better renal function at baseline. Nevertheless, AKI occurred numerically more often after SMVR than PMVR (25.8% vs. 17.9%, p=0.060), and a multivariable regression model adjusting for differences between both groups confirmed a significantly lower risk for AKI following PMVR (OR 0.22, 95% CI: 0.11-0.44, p<0.001). CONCLUSIONS: These data show a significant incidence of AKI after PMVR that must be taken into account in periprocedural care. Nevertheless, our data suggest that SMVR carries an even higher risk of AKI, which should be considered when a decision has to be made between the two therapies.

Bleeding Complications After Percutaneous Mitral Valve Repair With the MitraClip.

Bleeding after cardiac surgery or cardiovascular interventions is associated with worse patient outcome. Only very limited data are available on the subject of bleeding after percutaneous edge-to-edge mitral valve repair (PMVR). We performed a single center analysis including 347 consecutive patients who underwent PMVR. Bleeding was defined according to the Mitral Valve Academic Research Consortium (MVARC) end point definition. The incidence of MVARC bleeding was 21.6% (n = 75), whereas major MVARC bleeding (hemoglobin decrease ≥3 g/dl) occurred in 7.4% (n = 26). Only 33.3% of all bleeding cases were access site-related. In multivariate regression analyses, independent predictors of MVARC bleeding were the presence of coronary artery disease (2.809, 95% CI 1.123 to 7.022, p = 0.027) and intervention duration (1.010, 95% CI 1.002 to 1.018, p = 0.010). Patients experiencing MVARC bleeding had longer hospital stays (p = 0.026); however, neither major nor extensive MVARC bleeding was associated with increased 30-day or 1-year mortality. A decrease in hemoglobin levels ≥3 g/dl without clinically visible bleeding sign-not considered in the MVARC bleeding definition-occurred in 9.5% of patients. A hemoglobin decrease of ≥4 g/dl had a strong association with worse survival in those patients with obscure bleeding. In conclusion, these data show a relevant incidence of bleeding after PMVR. In contrast to other cardiovascular interventions, the majority of bleedings were not access site-related. Particularly, patients with obscure bleeding, which are not included in the MVARC end point definitions, had worse outcomes and should therefore be considered for a more intensive workup.

Short-term and long-term follow-up of pulmonary function in patients with COPD after total laryngectomy: A prospective study.

OBJECTIVE: There exists no standardized method for examining lung function in laryngectomized patients. STUDY DESIGN AND METHODS: We established a base plate adapter (BPA) system for patients after laryngectomy. In 10 patients with chronic obstructive pulmonary disease (COPD), we evaluated pulmonary function before laryngectomy, as well as 2 weeks and 3 months after laryngectomy. RESULTS: The BPA system was well tolerated and delivered reliable results comparable to measurements with a mouthpiece. The parameters forced expiratory volume in one second (FEV1 ), forced vital capacity (FVC), and mean forced expiratory flow between 25% and 75% of forced vital capacity (MFEF25-75 ) changed in the early postoperative examinations (2 weeks postoperative), whereas MFEF25-75 , FEF75 , peak expiratory flow (PEF), and peak inspiratory flow (PIF)) showed differences from baseline in long-term follow-up (3 months postoperative). CONCLUSION: We provide a practicable method of lung function testing in laryngectomized patients with COPD that is essential to tailor inhalation therapy despite tracheotomy. Lung function measurements of laryngectomized patients with COPD should be performed under stable clinical conditions a few weeks after surgery. Guidelines of COPD might be complemented considering the subgroup of laryngectomized patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2045-2049, 2017.

NFκB-Associated Pathways in Progression of Chemoresistance to 5-Fluorouracil in an In Vitro Model of Colonic Carcinoma.

BACKGROUND: Drug resistance to 5-fluorouracil (5-FU) is a major obstacle in colonic cancer treatment. Activation of nuclear factor-kappa B (NFκB), mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and protein kinase B (AKT) is thought to protect cancer cells against therapy-induced cytotoxicity. MATERIALS AND METHODS: Using cytotoxicity assays and immunoblotting, the impact of inhibitory strategies addressing NFκB, AKT and MAP3K8 in chemoresistance was evaluated in a colonic cancer model in vitro. This model consisted of the cell lines SW480 and SW620, and three subclones with increasing degrees of chemoresistance in order to mimic the development of secondary resistance. RESULTS: NFκB protein p65 was selectively activated in all resistant cell lines. Consequently, several inhibitors of NFκB, MAP3K8 and AKT effectively circumvented this chemoresistance. As a cellular reaction, NFκB inhibition may trigger a feedback loop resulting in activation of extracellular signal-regulated kinase. The results suggest that chemoresistance to 5-FU in this colonic carcinoma model (cell lines SW480 and SW620) is strongly dependent on NFκB activation. The efficacy of MAP3K8 inhibition in our model potentially uncovers a new mechanism to circumvent 5-FU resistance.