Elucidation of the genetic causes of bicuspid aortic valve disease.

AIMS: The present study aims to characterize the genetic risk architecture of bicuspid aortic valve (BAV) disease, the most common congenital heart defect. METHODS AND RESULTS: We carried out a genome-wide association study (GWAS) including 2236 BAV patients and 11 604 controls. This led to the identification of a new risk locus for BAV on chromosome 3q29. The single nucleotide polymorphism rs2550262 was genome-wide significant BAV associated (P = 3.49 × 10-08) and was replicated in an independent case-control sample. The risk locus encodes a deleterious missense variant in MUC4 (p.Ala4821Ser), a gene that is involved in epithelial-to-mesenchymal transformation. Mechanistical studies in zebrafish revealed that loss of Muc4 led to a delay in cardiac valvular development suggesting that loss of MUC4 may also play a role in aortic valve malformation. The GWAS also confirmed previously reported BAV risk loci at PALMD (P = 3.97 × 10-16), GATA4 (P = 1.61 × 10-09), and TEX41 (P = 7.68 × 10-04). In addition, the genetic BAV architecture was examined beyond the single-marker level revealing that a substantial fraction of BAV heritability is polygenic and ∼20% of the observed heritability can be explained by our GWAS data. Furthermore, we used the largest human single-cell atlas for foetal gene expression and show that the transcriptome profile in endothelial cells is a major source contributing to BAV pathology. CONCLUSION: Our study provides a deeper understanding of the genetic risk architecture of BAV formation on the single marker and polygenic level.

Artificial intelligence-enabled phenotyping of patients with severe aortic stenosis: on the recovery of extra-aortic valve cardiac damage after transcatheter aortic valve replacement.

OBJECTIVE: A novel artificial intelligence-based phenotyping approach to stratify patients with severe aortic stenosis (AS) prior to transcatheter aortic valve replacement (TAVR) has been proposed, based on echocardiographic and haemodynamic data. This study aimed to analyse the recovery of extra-aortic valve cardiac damage in accordance with this novel stratification system following TAVR. METHODS: The proposed phenotyping approach was previously established employing data from 366 patients with severe AS from a bicentric registry. For this consecutive study, echocardiographic follow-up data, obtained on day 147±75.1 after TAVR, were available from 247 patients (67.5%). RESULTS: Correction of severe AS by TAVR significantly reduced the proportion of patients suffering from concurrent severe mitral regurgitation (from 9.29% to 3.64%, p value: 0.0015). Moreover, pulmonary artery pressures were ameliorated (estimated systolic pulmonary artery pressure: from 47.2±15.8 to 43.3±15.1 mm Hg, p value: 0.0079). However, right heart dysfunction as well as the proportion of patients with severe tricuspid regurgitation remained unchanged. Clusters with persistent right heart dysfunction ultimately displayed 2-year survival rates of 69.2% (95% CI 56.6% to 84.7%) and 74.6% (95% CI 65.9% to 84.4%), which were significantly lower compared with clusters with little or no persistent cardiopulmonary impairment (88.3% (95% CI 83.3% to 93.5%) and 85.5% (95% CI 77.1% to 94.8%)). CONCLUSIONS: This phenotyping approach preprocedurally identifies patients with severe AS, who will not recover from extra-aortic valve cardiac damage following TAVR and whose survival is therefore significantly reduced. Importantly, not the degree of pulmonary hypertension at initial presentation, but the irreversibility of right heart dysfunction determines prognosis.

Harnessing feature extraction capacities from a pre-trained convolutional neural network (VGG-16) for the unsupervised distinction of aortic outflow velocity profiles in patients with severe aortic stenosis.

Aims: Hypothesizing that aortic outflow velocity profiles contain more valuable information about aortic valve obstruction and left ventricular contractility than can be captured by the human eye, features of the complex geometry of Doppler tracings from patients with severe aortic stenosis (AS) were extracted by a convolutional neural network (CNN). Methods and results: After pre-training a CNN (VGG-16) on a large data set (ImageNet data set; 14 million images belonging to 1000 classes), the convolutional part was employed to transform Doppler tracings to 1D arrays. Among 366 eligible patients [age: 79.8 ± 6.77 years; 146 (39.9%) women] with pre-procedural echocardiography and right heart catheterization prior to transcatheter aortic valve replacement (TAVR), good quality Doppler tracings from 101 patients were analysed. The convolutional part of the pre-trained VGG-16 model in conjunction with principal component analysis and k-means clustering distinguished two shapes of aortic outflow velocity profiles. Kaplan-Meier analysis revealed that mortality in patients from Cluster 2 (n = 40, 39.6%) was significantly increased [hazard ratio (HR) for 2-year mortality: 3; 95% confidence interval (CI): 1-8.9]. Apart from reduced cardiac output and mean aortic valve gradient, patients from Cluster 2 were also characterized by signs of pulmonary hypertension, impaired right ventricular function, and right atrial enlargement. After training an extreme gradient boosting algorithm on these 101 patients, validation on the remaining 265 patients confirmed that patients assigned to Cluster 2 show increased mortality (HR for 2-year mortality: 2.6; 95% CI: 1.4-5.1, P-value: 0.004). Conclusion: Transfer learning enables sophisticated pattern recognition even in clinical data sets of limited size. Importantly, it is the left ventricular compensation capacity in the face of increased afterload, and not so much the actual obstruction of the aortic valve, that determines fate after TAVR.

Subphenotyping of Patients With Aortic Stenosis by Unsupervised Agglomerative Clustering of Echocardiographic and Hemodynamic Data.

OBJECTIVES: The aim of this retrospective analysis was to categorize patients with severe aortic stenosis (AS) according to clinical presentation by applying unsupervised machine learning. BACKGROUND: Patients with severe AS present with heterogeneous clinical phenotypes, depending on disease progression and comorbidities. METHODS: Unsupervised agglomerative clustering was applied to preprocedural data from echocardiography and right heart catheterization from 366 consecutively enrolled patients undergoing transcatheter aortic valve replacement for severe AS. RESULTS: Cluster analysis revealed 4 distinct phenotypes. Patients in cluster 1 (n = 164 [44.8%]), serving as a reference, presented with regular cardiac function and without pulmonary hypertension (PH). Accordingly, estimated 2-year survival was 90.6% (95% CI: 85.8%-95.6%). Clusters 2 (n = 66 [18.0%]) and 4 (n = 91 [24.9%]) both comprised patients with postcapillary PH. Yet patients in cluster 2 with preserved left and right ventricular structure and function showed a similar survival as those in cluster 1 (2-year survival 85.8%; 95% CI: 76.9%-95.6%), whereas patients in cluster 4 with dilatation of all heart chambers and a high prevalence of mitral and tricuspid regurgitation (12.5% and 14.8%, respectively) died more often (2-year survival 74.9% [95% CI: 65.9%-85.2%]; HR for 2-year mortality: 2.8 [95% CI: 1.4-5.5]). Patients in cluster 3, the smallest (n = 45 [12.3%]), displayed the most extensive disease characteristics (ie, left and right heart dysfunction together with combined pre- and postcapillary PH), and 2-year survival was accordingly reduced (77.3% [95% CI: 65.2%-91.6%]; HR for 2-year mortality: 2.6 [95% CI: 1.1-6.2]). CONCLUSIONS: Unsupervised machine learning aids in capturing complex clinical presentations as observed in patients with severe AS. Importantly, structural alterations in left and right heart morphology, possibly due to genetic predisposition, constitute an equally sensitive indicator of poor prognosis compared with high-grade PH.

Changes of Right Ventricular Function After Transcatheter Aortic Valve Replacement and Association With Outcomes.

BACKGROUND: Baseline right ventricular (RV) dysfunction represents a predictor for poor outcome in patients undergoing transcatheter aortic valve replacement (TAVR). However, RV function may improve after TAVR, which could have important implications on outcomes. The aim of the present study was to assess changes in RV function after TAVR and its prognostic value regarding clinical outcome. METHODS AND RESULTS: Patients undergoing TAVR at our institution were consecutively enrolled and categorized into 4 groups according to changes in RV function during echocardiographic follow-up at 6 months. A total of 188 patients were included. Of those showing normal function at baseline, 87% (130/149) had preserved RV function at follow-up (group 1), whereas 13% (19/149) developed new RV dysfunction (group 2). Of those with RV dysfunction at baseline (39 patients), RV function normalized in 46% (18/39) (group 3) and remained impaired in 54% (21/39) (group 4). The Kaplan-Meier estimated survival at 3 years was highest in patients in group 1 (83%), intermediate in group 2 (65%) and 3 (69%), whereas group 4 had the worst survival (37%; P < .001). Furthermore, new or persistent RV dysfunction was identified to be independently associated with mortality during follow-up (hazard ratio 2.55; interquartile range 1.03-6.47, P = .004). CONCLUSIONS: Patients with preserved RV function have a high 3-year survival. Normalization of RV function showed improved survival compared with patients with persistent RV dysfunction, who had a dismal prognosis despite TAVR.

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Influence of diagnosis of venous thromboembolism on immature platelets, absolute platelet count and platelet aggregation over time.

The extent of the involvement of platelets in venous thromboembolisms (VTE) is still not fully understood. Immature platelets are large, RNA-rich, prothrombotic platelets. They are involved in arterial thromboembolisms and are associated with adverse cardiovascular events. Their role in VTE has not been investigated before. The aim of this study was to assess different platelet parameters including immature platelet fraction (IPF), immature platelet count (IPC), absolute platelet count and platelet aggregation (PA) over time in patients with VTE at time of diagnosis, as well as at 3-10 days and at 90-110 days after diagnosis. 50 healthy volunteers similar in age and sex to patients served as controls at diagnosis. IPF was measured by the Sysmex XE-5000 analyzer, PA was assessed using the Multiplate analyzer. Diagnosis of VTE had no relevant effect on IPF and IPC whereas absolute platelet count and PA were significantly decreased compared to controls. In the course of VTE, IPF decreased significantly, whereas IPC, absolute platelet count and PA increased. In conclusion, VTE was associated with relevant changes of the absolute platelet count and PA at diagnosis, as well as changes in IPF and IPC over time reflecting a relevant and measurable platelet consumption in VTEs.

Dose-Dependent Effect of Renin-Angiotensin System Blockade Following Transcatheter Aortic Valve Replacement.

BACKGROUND: There is growing body of evidence from retrospective studies that renin-angiotensin system (RAS) blockade is associated with improved outcome after transcatheter aortic valve replacement (TAVR). However, it remains unknown whether the effect of RAS blockade is dose dependent. The current study sought to assess the dose-dependent effect of RAS blockade on survival and left-ventricular (LV) remodelling after TAVR. METHODS: Patients who were enrolled into our observational TAVR study at our institution were retrospectively assessed according to different doses of RAS blockade: group 1 (no RAS blockade), group 2 (25% of maximum daily dose), group 3 (50% of maximum daily dose), and group 4 (full daily dose). RESULTS: A total of 323 patients between January 2015 and September 2019 were included. Patients with higher doses of RAS blockade showed a trend toward higher overall survival at 3-year follow-up (56% with no RAS blockade vs 66% with the 25% dose vs 79% with the 50% dose vs 78% with the full dose; P = 0.063). After adjustment for baseline characteristics, the difference in survival was significant (P = 0.042). Besides New York Heart Association class and left-ventricular ejection fraction (LVEF), RAS blockade dose was identified as independent predictor for all-cause mortality (hazard ratio [HR] 0.72; 95% confidence interval [CI], 0.54-0.97; P = 0.03). With respect to LV remodelling, a significantly larger reduction of LV mass index was observed during the follow-up with higher doses of RAS blockade. CONCLUSIONS: The current study showed that the impact of RAS blockade treatment on clinical outcome and LV remodelling after TAVR is dose dependent.

TAVR outcome after reclassification of aortic valve stenosis by using a hybrid continuity equation that combines computed tomography and echocardiography data.

BACKGROUND: In the continuity equation, assumption of a round-shaped left ventricular outflow tract (LVOT) leads to underestimation of the true aortic valve area in two-dimensional echocardiography. The current study evaluated whether inclusion of the LVOT area, as measured by computed tomography (CT), reclassifies the degree of aortic stenosis (AS) and assessed the impact on patient outcome after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Four hundred and twenty-two patients with indexed aortic valve area index (AVAi) of <0.6 cm2 /m2 , assessed by using the classical continuity equation (mean age: 81.5 ± 6.1 years, 51% female, mean left ventricular ejection fraction: 53.2 ± 13.6%), underwent TAVR and were included. After inclusion of the CT measured LVOT area into the continuity equation, the hybrid AVAi led to a reclassification of 30% (n = 128) of patients from severe to moderate AS. Multivariate predictors for reclassification were male sex, lower mean aortic gradient, and lower annulus/LVOT ratio (all p < .01). Reclassified patients had significantly higher sST2 at baseline and higher NT-proBNP values at baseline and 6 months follow-up compared to non-reclassified patients. Acute kidney injury was experienced more frequently after TAVR by reclassified patients, but no significant mortality difference occurred during 2 years of follow-up. CONCLUSION: The hybrid AVAi reclassifies a significant portion of low-gradient severe AS patients into moderate AS. Reclassified patients showed increased fibrosis and heart failure markers at baseline compared to non-reclassified patients. But reclassification had no significant impact on mortality up to 2 years after TAVR. Routine assessment of hybrid AVAi seems not to improve further risk stratification of TAVR patients.

Prognostic impact of cancer history in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The benefit of TAVI in cancer patients is currently unclear. OBJECTIVES: The purpose of this study is to investigate prognostic impact of cancer status (active cancer or previous cancer) in severe aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: Consecutive TAVI patients in the Heart Center Bonn were enrolled and we stratified the patients into three groups: current cancer (active cancer), non-current cancer (previous cancer), or no cancer. The primary outcome was all-cause death within a 5-year follow-up. We evaluated mean aortic pressure gradient (mPG) values following TAVI (baseline mPG) and at the final follow-up (follow-up mPG). RESULTS: In total, 1568 TAVI patients were eligible and 298 patients (19.0%) had active or previous cancer. At the 5-year follow-up, cancer patients had a significantly worse prognosis than non-cancer patients (log rank, P < 0.001). In a multivariable analysis, previous cancer was a significant predictor for 5-year mortality (hazard ratio [HR], 1.56; P < 0.001). Estimated mortality rates at 5-year follow-up rates among active cancer, previous cancer, and non-cancer were 84.0%, 65.8%, and 50.2% (long-rank P < 0.001), respectively. The hazard ratios of active cancer and previous cancer for 5-year mortality were 2.79 (P < 0.001) and 1.38 (P = 0.019) compared to non-cancer patients. We found significantly higher mPG during follow-up than at baseline in cancer patients (follow-up 8.10 vs baseline 7.40 mmHg; Wilcoxon P = 0.012). CONCLUSIONS: Active, and also previous, cancer status are associated with less beneficial long-term prognosis in TAVI patients.

Impact of transcatheter mitral valve repair using MitraClip on right ventricular remodeling.

The potential of the MitraClip to prevent from right heart failure or to restore right ventricular (RV) function is still unclear. The aim of the present study was to analyze the impact of the MitraClip implantation on RV function and its association with clinical outcome. After MitraClip implantation patients underwent echocardiography follow-up scheduled between 3 and 6 months after the procedure in the present single-center registry. A total of 93 patients were included. Compared to baseline, RV function declined in 20%, was unchanged in 25% and improved in 55% of the patients. Factors associated with decline in RV performance were atrial fibrillation, decrease in left ventricular function and lack of reduction in pulmonary artery pressure. Patients who experienced worsening in RV function had a significantly lower survival after mean follow-up of 11 ± 7 months compared to those with preserved or improved RV function (15% vs. 83% vs. 83%; p log rank = 0.001). Furthermore, changes in TAPSE were found to be an independent predictor for all-cause mortality [HR 0.88 (0.77-0.99); p = 0.04]. The majority of patients suffering from severe MR benefited from MitraClip with respect to RV remodeling. However, 20% of the patients experienced a decline in RV function, which was associated with poor prognosis. Importantly, changes in RV function after MitraClip were identified as independent predictor for survival in contrast to baseline RV function and, therefore, should be implemented in follow-up routine for better outcome prediction.

Fractional flow reserve in patients with coronary artery disease undergoing TAVI: a prospective analysis.

OBJECTIVES: To determine the true prevalence of CAD in AS patients, to detect changes of the hemodynamic significance of coronary lesions following TAVI, to explore to what extent FFR-positive CAD might influence outcome and finally to develop a management algorithm for this patient subset. METHODS: From May 2016 to March 2018, diagnostic coronary angiography was performed in 246 patients before TAVI. In the presence of coronary lesions with a diameter stenosis ≥ 50%, FFR was measured. In patients with positive FFR ≤ 0.80, a control angiography was performed 6-8 weeks after TAVI. RESULTS: The study cohort was 81.0 ± 6.1 years old, 48.4% of the patients were male. 53.3% had concomitant CAD. 35.9% of these patients underwent PCI before TAVI due to functionally significant left main CAD and/or severe stenosis ≥ 90%. 31 patients underwent FFR measurements in cumulative 38 coronary lesions. Prior to TAVI, a negative FFR could be detected in 18 lesions, whereas a positive FFR was found in entirely 20 lesions. A control angiography and FFR measurement was performed in cumulative 13 lesions. Comparing the FFR values, there was no significant difference (0.77 ± 0.04 vs. 0.76 ± 0.08; p = 0.11). CONCLUSION: Concomitant CAD was diagnosed in 53.3% of TAVI patients. FFR did not significantly change after TAVI, confirming the validity of FFR to evaluate coronary lesions in this specific clinical setting. Given the low rates of cardiac adverse events, it might therefore be considered to treat coronary stenoses not involving left main and those with a diameter stenosis < 90% after TAVI.

Peripheral perfusion of lower limb after transcatheter aortic valve implantation (TAVI) in patients with peripheral artery disease.

BACKGROUND: In TAVI patients, peripheral arterial disease (PAD) is a common concomitant disease. Given the fact that calcified severe aortic stenosis (AS) limits the blood flow that reaches the periphery, it is conceivable that the treatment of AS may positively influence the peripheral perfusion. AIM: To evaluate whether, and if so, how the peripheral perfusion changes after TAVI in patients with PAD comparing with patients without PAD. METHODS: On the basis of objective vascular tests, peripheral perfusion in the lower extremities were studied in 108 TAVI patients with or without concomitant PAD. RESULTS: 108 consecutive patients with a median logistic EuroSCORE of 12.7 (IQR: 8.5 to 22.0) % underwent TAVI with an extensive pre- and post-procedural assessment of the peripheral perfusion. In patients without PAD, the time to peak flow (tPF) did not differ before (6.45 ±â€¯5.24 s) and after (6.45 ±â€¯5.91 s) TAVI (p = 1.000). In PAD patients, however, the tPF was significantly shortened following TAVI (9.51 ±â€¯9.45 s vs. 8.33 ±â€¯8.16 s, p < 0.001), thereby reflecting an improvement in peripheral blood flow. The resting arterial blood flow before and after TAVI showed the highest level at the beginning (0 s) and constantly decreased afterwards. No improvement in the peak flow was achieved. CONCLUSIONS: In PAD patients, TAVI led to improved peripheral blood flow as reflected by shortened time to peak flow measurements.

Comparative study of pressure (ankle-brachial pressure index) and flow (strain gauge plethysmography and reactive hyperaemia) measurements in diagnosis of peripheral arterial disease in patients with severe aortic stenosis.

BACKGROUND: The measurement of the ankle-brachial pressure index is a straightforward method for the detection of peripheral disease in the lower limbs. Only a few old studies with small numbers of patients have been conducted comparing the gold standard, ankle-brachial pressure index measurement, with strain gauge plethysmography and reactive hyperaemia for detecting peripheral arterial disease. The purpose of this study was to evaluate the feasibility and accuracy of strain gauge plethysmography values compared with the Doppler ultrasound method, ankle-brachial pressure index, in the assessment of peripheral arterial disease, especially in patients with severe aortic stenosis. METHODS: 221 ankle-brachial pressure index measurements and strain gauge plethysmography measurements of patients with suspected peripheral arterial disease, diagnosed peripheral arterial disease with or without aortic stenosis were compared. RESULTS: Irrespective of aortic stenosis in patients with and without peripheral arterial disease, the resting arterial blood flow was within the normal range. In patients with aortic stenosis, the time-to-peak flow couldn't detect peripheral arterial disease and was found to be a false negative. In patients without aortic stenosis, time-to-peak flow correlated well with the ankle-brachial pressure index for detecting peripheral arterial disease. Peak flow at 5 seconds was the one of the flow values that correlated with ankle-brachial pressure index and detected peripheral arterial disease in patients with and without aortic stenosis. CONCLUSION: Peak flow at 5 seconds is one of flow value that correlated well with ankle-brachial pressure index in detecting peripheral arterial disease in patients with and without aortic stenosis. Detection of peripheral arterial disease in patients with severe aortic stenosis seems to be less sensitive with flow measurements than with ankle-brachial pressure index.

Early versus newer generation transcatheter heart valves for transcatheter aortic valve implantation: Echocardiographic and hemodynamic evaluation of an all-comers study cohort using the dimensionless aortic regurgitation index (AR-index).

AIMS: More than mild paravalvular aortic regurgitation (pAR) negatively impacts prognosis after transcatheter aortic valve implantation (TAVI). "Newer generation" transcatheter heart valves (THVs) including Direct Flow Medical, Medtronic Evolut R, Boston Lotus, and Edwards SAPIEN 3 valve system promise to improve outcome by reducing the rate of TAVI-related issues such as pAR. Aim was to evaluate and compare the hemodynamic performance with AR index of "early" vs. "newer generation" THVs and its impact on outcome. METHODS AND RESULTS: In 805 patients undergoing TAVI, the degree of pAR was assessed using imaging modalities (angiography, echocardiography) and hemodynamic measurements (aortic regurgitation index, ARI ratio). Severity of pAR and outcome were assessed according to the VARC-2 criteria. 805 patients underwent TAVI with use of the CoreValve (n = 400), SAPIEN XT (n = 48), Direct Flow Medical (n = 38), Evolut R (n = 114), Lotus (n = 104), or SAPIEN 3 (n = 101) prosthesis. TTE post TAVI revealed that a total of 7.3% of the patients showed moderate/severe pAR. The occurrence of greater than mild pAR occurred less frequently in patients treated with "newer generation" THVs (p<0.001): CoreValve (11.3%), SAPIEN XT (12.5%), Direct Flow Medical (5.3%), Evolut R (5.3%), Lotus (0.0%), and SAPIEN 3 (0.0%). The AR index was significantly higher (p<0.001) in patients receiving "newer generation" prostheses compared to those in whom "earlier generation" THVs were used. However, the ARI was only predictive of cumulative all-cause mortality at 1 and 3 years in "early generation", but not in "newer generation" THVs. In the overall cohort, 30-day and 1-year mortality was 4.8% and 20.1%, respectively. In patients treated with "newer generation" devices, the respective mortality rates remained substantially below those of patients treated with "earlier generation" THVs (30-day mortality: 2.5% vs. 6.7%, p< 0.001; 1-year mortality: 11.2% vs. 27.2%, p<0.001). CONCLUSION: TAVI with use of "newer generation" THVs showed significantly reduced pAR and improved outcomes compared to "early generation" devices that could at least in part be explained by more favorable hemodynamics.

Prognostic Impact of Left Atrial Function Following Transcatheter Mitral Valve Repair.

Background Left atrial ( LA ) function predicts clinical outcome in a variety of cardiovascular diseases. However, limited data are available in the setting of mitral regurgitation. The aim of the present study was to assess potential changes in LA ejection fraction (LAEF) and its prognostic value in patients following transcatheter mitral valve repair using the MitraClip. Methods and Results A total of 88 consecutive patients undergoing MitraClip implantation with complete echocardiography at baseline and follow-up between 3 and 6 months postprocedure were enrolled. LAEF improved in 58% of the population. Change in LAEF was associated with residual mitral regurgitation, residual transmitral gradient and left ventricular ejection fraction changes. Compared with their counterparts, patients with residual mitral regurgitation ≥grade 2 (change in LAEF, -6% [Interquartile [IQR], -9-1%] versus 4% [IQR, -5-15%]; P=0.05) and with residual transmitral gradient ≥5 mm Hg (change in LAEF, -2% [IQR, -9-9%] versus 5% [IQR, -4-16%]; P=0.03) showed a decline in LAEF , respectively. Furthermore, LAEF significantly correlated with changes in left ventricular ejection fraction ( r=0.40; P=0.001). With regards to clinical outcome, heart failure symptoms as assessed by New York Heart Association class were more severe in patients with worsened LAEF at follow-up. Finally, LAEF change was identified as an independent predictor of all-cause mortality (hazard ratio, 0.94; 95% CI, 0.90-0.98 [ P=0.008]). Conclusions The present analysis showed that changes in LA function in patients undergoing MitraClip implantation are associated with important measures including residual mitral regurgitation, elevated transmitral gradient, and left ventricular function. Importantly, LA function alterations represent a strong predictor for all-cause mortality.

Brief report - Telomere length is a poor biomarker to predict 1-year mortality or cardiovascular comorbidity in patients with transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a therapeutic option for patients with aortic valve stenosis at increased surgical risk. Telomeres are an established marker for cellular senescence and have served to evaluate cardiovascular diseases including severe aortic valve stenosis. In our study, we hypothesized that telomere length may be a predictor for outcome and associated with comorbidities in patients with TAVR. METHODS AND RESULTS: We analyzed leucocyte telomere length from 155 patients who underwent TAVR and correlated the results with 1-year mortality and severe comorbidities. The cohort was subdivided into 3 groups according to telomere length. Although a trend for a positive correlation of telomere length with a lower EuroSCORE could be found, telomere length was not associated with survival, aortic valve opening area or cardiovascular comorbidities (peripheral, coronary or cerebrovascular disease). Interestingly, long telomeres were significantly correlated to a reduced left ventricular ejection fraction (LVEF). CONCLUSION: In elderly patients with severe aortic valve stenosis, leucocyte telomere length did not predict post-procedural survival. The correlation between long telomere length and reduced LVEF in these patients deserves further attention.

Reverse Cardiac Remodeling After Transcatheter Treatment of Severe Tricuspid Regurgitation Using the Edge-to-Edge MitraClip Technique.

OBJECTIVES: In recent years, transcatheter treatment techniques for tricuspid regurgitation (TR) have rapidly evolved. Cardiac remodeling analysis beyond clinical outcome assessment following transcatheter tricuspid repair is still lacking. The aim of the present case series was to analyze cardiac remodeling after tricuspid valve repair using the edge-to-edge MitraClip technique. METHODS: Echocardiographic analysis was performed prior to MitraClip implantation and at 3-month and 6-month follow-up exams. RESULTS: Six consecutive patients undergoing MitraClip implantation between April 2017 and March 2018 at our institution were enrolled. During follow-up, TR reduction was durable in all patients, without recurrence of severe TR. Compared to baseline, right ventricular function improved in 5 out of 6 patients. Reduction in right ventricular area was observed in the majority of patients and reduction in right atrial volume was observed in all subjects. Patients also experienced beneficial left cardiac remodeling. CONCLUSION: The present series indicates that transcatheter treatment of severe TR using the edge-to-edge MitraClip technique can lead to reverse cardiac remodeling, which is not commonly seen in surgically treated patients.

Long-term follow-up after stent graft placement for access-site and access-related vascular injury during TAVI - The Bonn-Copenhagen experience.

AIMS: Stent graft placement is a safe and effective treatment option for vascular complications in the context of transcatheter aortic valve implantation (TAVI). This study aimed to provide long-term angiological follow-up of stent grafts used for this indication. METHODS AND RESULTS: Seventy-one patients (64.8% female, log EuroScore 14.7 ±â€¯6.8%) who had undergone TAVI between March 2010 and October 2015 with implantation of a Viabahn or Fluency stent graft to treat access-site or access-related vascular injury (ASARVI) were analyzed. Implantations were mostly due to access-site bleeding complications (83.1%) in the common femoral artery (97.1%). Follow-up was performed with duplex sonography in all patients after a median of 3.9 years after TAVI (interquartile range [IQR]: 895-1749 days). Ultrasound revealed tri- or biphasic flow patterns in 16.9% and 77.6%, respectively. Stent graft patency was 100% without signs of stent graft stenosis (mean peak velocity ratio 1.0 ±â€¯0.2). Pseudo-aneurysms or endoleaks were diagnosed in 5.6% of patients. Additional fluoroscopic and/or computed tomography (CT)-imaging was available in 36.6% of patients and did not reveal any stent fracture. CONCLUSION: Self-expanding stent grafts provide excellent long-term function with few complications when implanted in the context of TAVI-related ASARVI.