Assessment of tissue perfusion of pancreatic cancer as potential imaging biomarker by means of Intravoxel incoherent motion MRI and CT perfusion: correlation with histological microvessel density as ground truth

Background/objectives The aim of this study was to compare intravoxel incoherent motion (IVIM) diffusion weighted (DW) MRI and CT perfusion to assess tumor perfusion of pancreatic ductal adenocarcinoma (PDAC). Methods In this prospective study, DW-MRI and CT perfusion were conducted in nineteen patients with PDAC on the day before surgery. IVIM analysis of DW-MRI was performed and the parameters perfusion fraction f, pseudodiffusion coefficient D*, and diffusion coefficient D were extracted for tumors, upstream, and downstream parenchyma. With a deconvolution-based analysis, the CT perfusion parameters blood flow (BF) and blood volume (BV) were estimated for tumors, upstream, and downstream parenchyma. In ten patients, intratumoral microvessel density (MVDtumor) and microvessel area (MVAtumor) were analyzed microscopically in resection specimens. Correlation coefficients between IVIM parameters, CT perfusion parameters, and histological microvessel parameters in tumors were calculated. Receiver operating characteristic (ROC) analysis was performed for differentiation of tumors and upstream parenchyma. Results ftumor significantly positively correlated with BFtumor (r = 0.668, p = 0.002) and BVtumor (r = 0.672, p = 0.002). There were significant positive correlations between ftumor and MVDtumor/ MVAtumor (r ≥ 0.770, p ≤ 0.009) as well as between BFtumor and MVDtumor/ MVAtumor (r ≥ 0.697, p ≤ 0.025). Correlation coefficients between ftumor and MVDtumor/ MVAtumor were not significantly different from correlation coefficients between BFtumor and MVDtumor/ MVAtumor (p ≥ 0.400). Moreover, f, BF, BV, and permeability values (PEM) showed excellent performance in distinguishing tumors from upstream parenchyma (area under the ROC curve ≥0.874). Conclusions The study shows that IVIM derived ftumor and CT perfusion derived BFtumor similarly reflect vascularity of PDAC and seem to be comparably applicable for the evaluation of tumor perfusion for tumor characterization and as potential quantitative imaging biomarker

Impact of tricuspid regurgitation and its postprocedural reduction on long term outcome in patients undergoing percutaneous mitral valve edge to edge repair

Abstract Background Prevalence of functional tricuspid valve regurgitation (TR) in the adult population is high and mostly considered as a consequence of left-sided heart failure. In patients with moderate-to-severe and severe mitral regurgitation (MR), relevant concomitant TR is found in about 30–50%. For many years the concept of a reduction of secondary TR after mitral valve surgery has been widely accepted. However, more recently, compelling data have shown that surgically untreated functional TR can persist or even worsen despite the correction of the associated left-sided lesion. In line with previous research, studies have indicated that preexisting concomitant TR is an independent predictor for adverse outcome in patients undergoing percutaneous mitral valve Edge-to-Edge Repair (pMVR). Purpose This study intends to determine the extent to which the severity of tricuspid regurgitation, measured six months after pMVR, impacts the outcome. Methods Between September 2008 and July 2018, 805 consecutive patients with moderate-to-severe or severe MR underwent pVMR therapy with the MitraClip device at our center. We exclude patients with missing date of follow-up (n=54) and patients with missing values for baseline tricuspid regurgitation (n=93). We analyze, therefore, data of 658 patients with a median follow-up time of 4.93 (4.2, 4.99) years. Severity of TR was evaluated at baseline and six months after pMVR. Results Among 658 high-risk patients (mean age 75.4±8.7 years, 59.7% male, median STS Score 3.9 [2.4, 6.1]), 248 patients were suffering from no/mild (37.6%), 213 from moderate (32.6%) and 197 patients from severe (29.9%) TR. Functional MR was present in 429 (65.5%) patients. Procedural success was achieved in the majority of patients (no/mild TR 90.3%, moderate TR 91.1%, severe TR 90.4%). Overall, mortality rates up to two-year follow-up were highest for patients with severe TR (no/mild TR 30.2%, moderate TR 37.6%, severe TR 42.6%, p=0.023). The risk for overall mortality (Kaplan-Meier analysis, p=0.0027, Figure 1) was related to increasing TR severity. However, Kaplan-Meier analysis showed no relevant differences for the combined endpoint of death and rehospitalization (p=0.058). Interestingly, in a pairwise comparison, the risk for patients with pre-existing severe TR and postprocedural reduction to mild or moderate TR (n=17) was reduced for the combined endpoint (p=0.021) compared to patients with persistent severe TR (n=28). Conclusion Moderate and severe TR in high-risk patients undergoing pMVR is associated with an increased risk for overall mortality. While preliminary, the presented data suggest a favorable outcome in patients with a postprocedural reduction in the severity of TR. The results of this study indicate the importance of developing new therapeutic strategies in high-risk patients with combined MR and TR, probably leading to concomitant tricuspid valve interventions. Figure 1 Funding Acknowledgement Type of funding source: None </jats:sec

Tricuspid Regurgitation Disease Stages and Treatment Outcomes After Transcatheter Tricuspid Valve Repair

BACKGROUND: Tricuspid transcatheter edge-to-edge repair (T-TEER) has emerged as a treatment option for patients with severe tricuspid regurgitation (TR). However, randomized trials have not shown a survival benefit, possibly because of the inclusion of patients in an early or too advanced disease stage. OBJECTIVES: The authors sought to investigate the association between disease stage and outcomes following T-TEER. METHODS: In total, 1,885 patients with significant TR were analyzed, including 585 conservatively treated individuals and 1,300 patients who received T-TEER. Patients were evaluated as part of the prospective EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation) registry and grouped into early, intermediate, and advanced disease stage. Disease stage was based on left and right ventricular function, renal function, and natriuretic peptide levels. The stratification was validated in an external cohort. The primary endpoint was 1-year mortality. RESULTS: Overall, 395 patients (21% [395/1,885]) were categorized as early, 1,173 patients (62% [1,173/1,885]) as intermediate, and 317 patients (17% [317/1,885]) as advanced disease stage. In patients with early and advanced disease, mortality did not differ between interventional and conservative treatment (early-stage HR: 0.78; 95% CI: 0.34-1.80; P = 0.54; advanced stage HR: 1.06; 95% CI: 0.71-1.60; P = 0.78). However, mortality was significantly lower in patients undergoing percutaneous treatment with intermediate disease stage (HR: 0.73; 95% CI: 0.52-0.99; P = 0.03). CONCLUSIONS: Compared to medically treated controls, T-TEER was associated with 1-year survival at intermediate stage disease but not at early or advanced disease stages. The timing of T-TEER with regard to disease stages might be crucial to optimize treatment benefits

Acute hemodynamic changes and long term prognostic impact of pulmonary hypertension in patients undergoing percutaneous mitral valve edge to edge repair

Abstract Background Pulmonary hypertension (PH) due to left heart disease is the most common form of PH. Published literature suggests increased perisurgical mortality in patients undergoing surgical repair in the setting of preexisting PH. The data on the impact of preexisting PH on clinical outcomes after percutaneous Mitral Valve Edge-to-Edge Repair (pMVR) is limited to observational studies and rely mostly on echocardiographic data. Purpose The aim of the current study is to evaluate the influence of preexisting PH in patients undergoing pMVR analyzing periprocedural invasive right heart catheterization data. Methods Between September 2008 and July 2018, a total of 911 patients with moderate-to-severe or severe mitral regurgitation (MR) underwent pMVR at our center. This analysis includes 331 patients with a complete data set for pre- and postprocedural right heart catheterization and echocardiographic assessment as well as available follow-up information after the implantation. Patients are divided according to the etiology of PH. The combined primary endpoint consists of all-cause mortality and rehospitalization for heart failure. Furthermore, a sub-analysis is performed for all patients with preexisting post-capillary PH. Patients with post-capillary PH are divided into two groups based on a postprocedural decrease of pulmonary artery wedge pressure (mPAWP) below the threshold of 15mmHg. Univariate and multivariate Cox regression analyses are performed to assess the influence on long-term outcome. Results Of all 331 patients (57.7% [n= 191] male) undergoing pMVR, 195 (62.1%) had functional MR. Median ejection fraction was 40.5% (29.3, 54.0). Patients were followed-up for a maximum of 4.41 years and the median follow-up time was 1.98 years. Preexisting PH (mean pulmonary artery pressure ≥25 mmHg) was found in 236 (71.1%) patients: 49 patients had pre-capillary PH (≤15 mmHg), 187 had post-capillary PH (pcPH; n=183; mPAWP &amp;gt;15 mmHg). In Kaplan-Meier analysis, no statistically significant difference could be found in overall mortality in patients without or with PH, irrespective of etiology (p=0.43). However, in patients suffering from post-capillary PH, patients with a postprocedural reduction of mPAWP below the threshold of 15mmHg showed a significantly lower risk for overall long-term mortality compared to patients without a relevant mPAWP reduction (p=0.018). Multivariate analysis revealed acute postprocedural decrease of mPAWP below 15mmHg in patients with post-capillary PH to have a significant influence on mortality (HR 2.81 [1.35, 5.86]; p=0.006; Figure 1). Conclusion In contrast to previously published findings, the present results were not able to show a significant impact of PH, disregarding its etiology, on outcome. Nevertheless, a postprocedural decrease of mPAWP below 15mmHg in patients with post-capillary PH is associated with a favorable outcome. Figure 1 Funding Acknowledgement Type of funding source: None </jats:sec

Early results of a real-world series with two transapical transcatheter mitral valve replacement devices

Aims!#!Transcatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices.!##!Methods and results!#!A total of 11 patients were treated with the Tendyne™ (N = 7) or the Tiara™ TMVR systems (N = 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions. The study cohort [age 77 years (73, 84); 27.3% male] presented with primary (N = 4), secondary (N = 5) or mixed (N = 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk [logEuroSCORE II 8.1% (4.0, 17.4)]. Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (N = 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%.!##!Conclusions!#!TMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement

Early results of a real-world series with two transapical transcatheter mitral valve replacement devices

AbstractAimsTranscatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices.Methods and resultsA total of 11 patients were treated with the Tendyne™ (N = 7) or the Tiara™ TMVR systems (N = 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions.The study cohort [age 77 years (73, 84); 27.3% male] presented with primary (N = 4), secondary (N = 5) or mixed (N = 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk [logEuroSCORE II 8.1% (4.0, 17.4)]. Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (N = 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%.ConclusionsTMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement.Graphic abstract</jats:sec

Long-Term survival and functional status in patients with elevated mitral valve pressure gradient after transcatheter mitral valve repair

Abstract Background A growing number of patients are currently treated for severe mitral regurgitation (MR) using a transcatheter mitral valve repair (TMVr). In clinical routine, the potential risk of elevated post-procedural mitral valve pressure gradient (MPG) may prohibit optimal MR reduction driven by the avoidance of additional clip implantations. Thus, the unfavorable impact on survival and functional outcome of increased MPG in patients undergoing TMVr is currently debatable. Methods In this single-center, prospective study, survival and functional outcome of 780 consecutive patients with severe MR undergoing TMVr between September 2008 and January 2020 were investigated. After exclusion of patients with unsuccessful procedure and those lost to follow-up, data of 676 patients with a median follow-up time of 5.26 (5.11, 5.51) years were analyzed. MPG was determined by transthoracic echocardiography at discharge and considered elevated in excess of 4.5 mmHg. Kaplan-Meier analysis as well as multivariable Cox regression models were performed for the impact on elevated MPG on 5-year outcomes for the subgroups of functional MR (FMR) and degenerative MR (DMR). The primary outcome measure was a combined endpoint of death or rehospitalization for congestive heart failure. Results Among 676 patients undergoing TMVr (mean age 74.6±8.5 years, 59.0% male, median STS Score 3.9 [interquartile range 2.5; 6.0]), 179 (26.4%) patients had elevated MPG &amp;gt;4.5 mmHg. FMR was present in 426 (63.0%) patients. In the overall patient cohort, Kaplan-Meier and Cox Regression analyses could not demonstrate significant differences for the combined endpoint (p=0.99). In contrast, subgroup analysis according to MR etiology indicated a significant adverse influence of elevated MPG on the combined endpoint as well as functional outcome in patients with DMR, but not with FMR (Figure 1). After adjustment, multivariate Cox Regression analysis showed an inferior prognosis in patients with DMR and elevated MVPG &amp;gt;4.5 mmHg (hazard ratio 1.79 [1.17, 2.72], p=0.0069, Figure 2). Conclusions TMVr-patients with DMR and measurable elevated post-procedural MVPG face an inferior prognosis and reduced functional outcomes compared to patients with FMR. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2 </jats:sec