Alexander Sedaghat

Aortic regurgitation index defines severity of peri-prosthetic regurgitation and predicts outcome in patients after transcatheter aortic valve implantation.

OBJECTIVES The aim of this study was to provide a simple, reproducible, and point-of-care assessment of peri-prosthetic aortic regurgitation (periAR) during transcatheter aortic valve implantation (TAVI) and to decipher the impact of this peri-procedural parameter on outcome. BACKGROUND Because periAR after TAVI might be associated with adverse outcome, precise quantification of periAR is of paramount importance but remains technically challenging. METHODS The severity of periAR was prospectively evaluated in 146 patients treated with the Medtronic CoreValve (Minneapolis, Minnesota) prosthesis by echocardiography, angiography, and measurement of the aortic regurgitation (AR) index, which is calculated as ratio of the gradient between diastolic blood pressure (DBP) and left ventricular end-diastolic pressure (LVEDP) to systolic blood pressure (SBP): [(DBP - LVEDP)/SBP] × 100. RESULTS After TAVI, 53 patients (36.3%) showed no signs of periAR and 71 patients (48.6%) showed only mild periAR, whereas 18 patients (12.3%) and 4 patients (2.7%) suffered from moderate and severe periAR, respectively. The AR index decreased stepwise from 31.7 ± 10.4 in patients without periAR, to 28.0 ± 8.5 with mild periAR, 19.6 ± 7.6 with moderate periAR, and 7.6 ± 2.6 with severe periAR (p < 0.001), respectively. Patients with AR index <25 had a significantly increased 1-year mortality risk compared with patients with AR index ≥25 (46.0% vs. 16.7%; p < 0.001). The AR index provided additional prognostic information beyond the echocardiographically assessed severity of periAR and independently predicted 1-year mortality (hazard ratio: 2.9, 95% confidence interval: 1.3 to 6.4; p = 0.009). CONCLUSIONS The assessment of the AR index allows a precise judgment of periAR, independently predicts 1-year mortality after TAVI, and provides additional prognostic information that is complementary to the echocardiographically assessed severity of periAR.

Decrease of pulmonary hypertension impacts on prognosis after transcatheter aortic valve replacement.

AIMS Transcatheter aortic valve replacement (TAVR) is established as a treatment strategy for patients with end-stage aortic stenosis, many of whom are suffering from severe pulmonary hypertension (PH). In cardiac surgery patients, PH is associated with less symptomatic improvement and increased late mortality. This study elucidates the impact of PH on outcome after TAVR. METHODS AND RESULTS Pre and 90 days post-TAVR, pulmonary artery systolic pressure (PASP) was determined non-invasively by echocardiography in 353 patients undergoing TAVR. PH was classified as absent (<30 mmHg), mild-to-moderate (30-60 mmHg), and severe (>60 mmHg). Three hundred and fifty-three patients at high surgical risk, indicated by a logistic EuroSCORE of 26.6±16.5%, underwent TAVR. The severity of PH before TAVR was related to outcome with two-year mortality rates of 13.9%, 27.3%, and 48.4% for PASP <30 mmHg, 30-60 mmHg, and >60 mmHg, respectively (p=0.001). In patients with baseline PASP >60 mmHg, PASP decreased from 65.6±7.6 mmHg to 49.5±14.0 mmHg (p<0.001) at 90 days after TAVR. Patients with persistent severe PH had a worse prognosis than patients with a decrease of PASP below 60 mmHg (two-year mortality rate: 50.0% vs. 18.6%; p=0.001). CONCLUSIONS Severe pulmonary hypertension predicts adverse outcome after TAVR. Reduction of PASP after the procedure is associated with favourable prognosis.

In vitro assessment of the influence of aortic annulus ovality on the hydrodynamic performance of self-expanding transcatheter heart valve prostheses

BACKGROUND Although CT-studies as well as intraoperative analyses have described broad anatomic variations of the aortic annulus, which is predominantly found non-circular, commercially available transcatheter aortic heart valve prostheses are circular. In this study, we hypothesize that the in vitro hydrodynamic function of a self-expanding transcatheter heart valve (Medtronic CoreValve) assessed in an oval compartment representing the aortic annulus will differ from the conventionally used circular compartment. METHODS Medtronic CoreValve prostheses were tested in specifically designed and fabricated silicone compartments with three degrees of defined ovalities. The measurements were performed in a left heart simulator at three different flow rates. In this setting, regurgitation flow, effective orifice area, and systolic pressure gradient across the valve were determined. In addition, high speed video recordings were taken to investigate leaflet kinematics. RESULTS The pressure difference across the prosthesis increased with rising ovality. The effective orifice areas were only slightly impacted. The analyses of the regurgitation showed minor changes and partially lower regurgitation when switching from round to slightly oval settings, followed by strong increases for further ovalization. The high speed videos show minor central leakage and impaired leaflet apposition for strong ovalities, but no leaflet/stentframe contact in any setting. CONCLUSION This study quantifies the influence of oval expansion of transcatheter heart valve prostheses on their hydrodynamic performance. While slight ovalities were well tolerated by a self-expanding prosthesis, more significant ovality led to worsening of prosthesis function and regurgitation.

Doppler-based renal resistance index for the detection of acute kidney injury and the non-invasive evaluation of paravalvular aortic regurgitation after transcatheter aortic valve implantation

AIMS Acute kidney injury (AKI) is a strong but rather late predictor of mortality after transcatheter aortic valve implantation (TAVI). Early clinically useful markers for the detection of AKI and prediction of outcome are needed in order to control and improve management of periprocedural complications after TAVI. The aim of our study was to assess the predictive value of the Doppler-based renal resistance index (RRI), which correlates inversely with effective renal blood flow and creatinine clearance, for AKI in patients undergoing TAVI and to evaluate its association with paravalvular aortic regurgitation (PAR). METHODS AND RESULTS TAVI was performed with the Medtronic CoreValve prosthesis in 132 consecutive high-risk patients (mean logistic EuroSCORE: 30.3±18.2%). RRI, serum creatinine and cystatin C level were determined before, and 4 hrs, 24 hrs, 48 hrs, 72 hrs, and 7 days after TAVI. AKI occurred in 32/132 patients (24.2%). While serum creatinine and cystatin C levels decreased at first after TAVI (also in most patients developing AKI), the RRI increased significantly immediately after the procedure from 0.79±0.09 to 0.87±0.12 in patients developing AKI (p=0.003). A RRI >0.85 predicted post-interventional AKI with a sensitivity of 58% and specificity of 86%, and was superior to the serum creatinine level (p<0.001). In addition, an elevated RRI was significantly related to haemodynamic changes after TAVI and was associated with the occurrence of moderate/severe PAR (p<0.001). CONCLUSIONS Measurement of the Doppler-based RRI predicts risk for AKI and increased mortality rates at an early post-procedural time point and is related to the occurrence of more-than-mild paravalvular aortic regurgitation after TAVI.

Hydrodynamic Performance of the Medtronic CoreValve and the Edwards SAPIEN XT Transcatheter Heart Valve in Surgical Bioprostheses: An In Vitro Valve-in-Valve Model

BACKGROUND Valve-in-valve transcatheter aortic valve replacement (TAVR) is becoming a valuable option with promising clinical results in failed bioprosthetic heart valves. Sizing recommendations are based on size compatibility rather than on broad clinical data, in vitro measurements, or biomechanical evidence. The hemodynamic performance of transcatheter heart valves within degenerated surgical heart valves is unknown. METHODS We evaluated the in vitro hydrodynamic performance of two commercially available transcatheter heart valves (Medtronic CoreValve [Medtronic, Minneapolis, MN] and Edwards SAPIEN XT [Edwards Lifesciences, Irvine, CA]) in two different bioprosthetic aortic valves (Edwards Perimount [Edwards Lifesciences] and St. Jude Trifecta [St. Jude Medical, St. Paul, MN]). RESULTS Within the Edwards Perimount (23 mm) prosthesis, pressure gradients were higher for the SAPIEN XT compared with the CoreValve (11.2 ± 0.1 mm Hg versus 10.1 ± 0.1 mm Hg, p < 0.01), whereas effective orifice area (1.99 ± 0.01 cm(2) versus 1.80 ± 0.01 cm(2), p < 0.01) and total paravalvular leakage (9.0% ± 1.0% versus 5.4% ± 1.3%, p < 0.01) were increased when using the CoreValve. Similarly, measurements in the St. Jude Trifecta revealed higher transvalvular pressure gradients (13.0 ± 0.2 mm Hg versus 10.9 ± 0.3 mm Hg, p < 0.01) and lower effective orifice area for the SAPIEN XT compared with the CoreValve. However, total relative regurgitation was higher with SAPIEN XT as compared with the CoreValve in St. Jude Trifecta prostheses (11.2% ± 1.4% versus 8.3% ± 0.9%, p < 0.01). CONCLUSIONS Both transcatheter heart valve prostheses performed well in the described valve-in-valve settings. Hydrodynamic results were in line with the International Organization for Standardization standards for all configurations. The observed differences indicate a necessity for preclinical valve-in-valve tests in addition to clinical long-term data about longevity.

Pre-Procedural Hemodynamic Status Improves the Discriminatory Value of the Aortic Regurgitation Index in Patients Undergoing Transcatheter Aortic Valve Replacement

OBJECTIVES The aims of this study were to increase the discriminatory value of the aortic regurgitation index (ARI) for the assessment of paravalvular regurgitation (PVR) and to further elucidate the association between aortic regurgitation severity and mortality after transcatheter aortic valve replacement (TAVR). BACKGROUND Hemodynamic parameters such as the ARI complement predominantly angiographically guided TAVR. However, the ARI depends on several baseline and periprocedural characteristics. METHODS The ARI was prospectively calculated before and after TAVR in 600 patients. The severity of PVR was assessed in all patients by angiography and echocardiography according to a 3-class scheme. To account for pre-procedural hemodynamic status, the ARI ratio was calculated as post- over pre-procedural ARI. RESULTS Apart from the degree of PVR (β = -0.396, p < 0.001), pre-procedural hemodynamic status in the form of the ARI before TAVR (β = 0.227, p < 0.001) was associated with post-procedural ARI in multivariate regression analysis. The ARI ratio increased the specificity of post-procedural ARI alone for the prediction of both more than mild PVR and 1-year mortality from 75.1% to 93.2% and from 75.0% to 93.3%, respectively. Patients with post-procedural ARI values <25 after TAVR had significantly increased 1-year mortality only when the ARI ratio was <0.60 (50.0% vs. 26.3%, p = 0.001). CONCLUSIONS The ARI ratio integrating pre- and post-procedural hemodynamic status increases the discriminatory value of post-procedural ARI. The ARI ratio, which reflects acute hemodynamic changes after TAVR, is useful to identify patients with negative outcomes.

Balloon post-dilation and valve-in-valve implantation for the reduction of paravalvular leakage with use of the self-expanding CoreValve prosthesis.

AIMS The aims of the study were to evaluate balloon post-dilation (BPD) and valve-in-valve (ViV) implantation for the reduction of paravalvular leakage (PVL) in patients undergoing transcatheter aortic valve implantation (TAVI) with use of the self-expanding CoreValve prosthesis and to assess whether the aortic regurgitation (AR) index can be used to quantify the reduction of PVL by these corrective measures. METHODS AND RESULTS Angiography and the AR index were used to evaluate the severity of PVL before and after corrective measures in patients suffering from more than mild PVL. Corrective measures were performed in 44.7% (101/226 patients): BPD was performed in 85 patients and ViV implantation in 16 patients, respectively. In 86% (87/101 patients), PVL reduction was successful (no or mild PVL). BPD increased the AR index from 19.1±11.0 to 25.9±5.8 (p<0.001) and ViV implantation from 17.6±6.4 to 29.5±9.1 (p=0.008). One-year mortality (21.6% vs. 17.6% vs. 25.0%; p=0.69) and procedural stroke rate (2.4% vs. 2.4% vs. 0%; p=0.82) were not different between patients without corrective measures compared to patients who had undergone corrective measures (BPD or ViV). CONCLUSIONS BPD and ViV implantation are safe and effective to reduce PVL in TAVI patients. The AR index is useful to quantify the success of these corrective measures for PVL reduction objectively.

TAVI induces an elevation of hemostasis-related biomarkers, which is not causative for post-TAVI thrombocytopenia

BACKGROUND Thrombocytopenia after transcatheter aortic valve implantation (TAVI) has been evaluated in several studies, but the pathomechanisms behind this phenomenon are not well described. Here, we assess the influence of TAVI on hemostasis-related biomarkers and their potential role in post-TAVI thrombocytopenia. METHODS AND RESULTS We assessed perioperative platelet counts in 307 patients undergoing transfemoral TAVI. Additionally, hemostasis-related biomarkers including thrombin-anti-thrombin complex (TAT), prothrombin activation fragment 1+2 (F1+2), plasmin-α₂-antiplasmin complex (PAP), and d-dimer were assessed in a subcohort of 35 patients. The course of these parameters was correlated with platelet counts and compared in patients with and without a relevant thrombocytopenia, i.e., a decline in platelet count of ≥50% compared to baseline. Levels of TAT (8.6±8.7μg/l), PAP (992±597μg/l), and d-dimer (1.43±1.66mg/l) were elevated above normal range before TAVI. TAT, F1+2, and d-dimer significantly increased after TAVI, and d-dimer as well as PAP remained elevated until day 7, indicating TAVI-induced increased thrombin formation associated with secondary fibrinolysis. Post-TAVI thrombocytopenia occurred in 17.9% of patients and was associated with a significantly higher incidence of post-TAVI complications, e.g. acute kidney injury and vascular complications. No impact of activated coagulation on thrombocytopenia was observed. CONCLUSIONS TAVI induces an increase in hemostasis-related biomarkers, which persists until 1week after the procedure. The frequent finding of post-TAVI thrombocytopenia appears not to be linked to increased thrombin formation.

Routine Endovascular Treatment With a Stent Graft for Access-Site and Access-Related Vascular Injury in Transfemoral Transcatheter Aortic Valve Implantation

Background—Access-site and access-related vascular injury (ASARVI) is still a major limiting factor in transcatheter aortic valve implantation and affects the outcome of patients. Management strategies for ASARVI include manual compression, stent grafts, and vascular surgery. We hypothesized that the standard use of a self-expanding stent graft for the management of ASARVI is feasible and safe. Methods and Results—Of 407 patients treated by transfemoral transcatheter aortic valve implantation, 110 experienced ASARVI (27.0%). Of these, 96 (87.3%) were managed by the implantation of a self-expanding nitinol stent graft. In the majority of patients, minor vascular complications triggered the implantation of a stent graft (86.5%), mainly because of bleeding (90.6%) and dissection (5.2%) of the common femoral artery with high rates of primary treatment success (97.9%). Patients receiving stent grafts were more often female (62.2 versus 45.6%, P<0.01), had higher body mass indices (27.8±6.7 versus 25.7±4.7, P=0.01), and suffered more often from diabetes mellitus (34.4 versus 24.5%, P=0.04). Angiographic assessment after a median follow-up of 345 days (interquartile range, 23–745 days) revealed only one patient with moderate, asymptomatic instent-stenosis (1.0%). Compared with a propensity score–matched cohort of patients without ASARVI, stented patients had comparable long-term mortality, despite the occurrence of a vascular complication (1-year mortality: 17.7% versus 26.6%; stent versus matched cohort, respectively; P=0.1). Conclusions—Routine use of a self-expanding nitinol stent graft in selected patients experiencing ASARVI after transcatheter aortic valve implantation is feasible, safe, and associated with favorable short- and midterm clinical outcome.

Transcatheter aortic valve implantation leads to a restoration of von Willebrand factor (VWF) abnormalities in patients with severe aortic stenosis – Incidence and relevance of clinical and subclinical VWF dysfunction in patients undergoing transfemoral TAVI

BACKGROUND In this study, we sought to analyze the incidence and relevance of von Willebrand factor (VWF) abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI), especially on perioperative bleeding. Furthermore, we hypothesized that, similar to aortic valve surgery, TAVI results in a restoration of VWF abnormalities. METHODS AND RESULTS We performed a prospective analysis of periinterventional VWF parameters in 74 patients (80±7years, female in 37.5%) undergoing transfemoral TAVI for severe symptomatic aortic valve stenosis. At baseline, VWF:Ag was 210±90IU/dl with a mean VWF activity of 166±106IU/dl; activity-to-antigen ratio was 0.85±0.45. Heydes syndrome (severe aortic stenosis plus GI bleeding from angiodyplasia) was observed in 2/74 (2.7%). Whereas preprocedural loss of high-molecular-weight (HMW) VWF multimers was found in thirty-six patients (48.6%), none of the patients fulfilled criteria for possible acquired VW syndrome. After TAVI, an increase of both VWF:Ag and activity compared to baseline was observed (p<0.01). In patients with HMW multimer loss, post-interventional recovery of multimers occurred in all cases. In the two patients with Heydes syndrome, a trend towards reduced VWF:Ag was seen, with loss of HMW multimers in one patient. Of interest, all patients suffering from periprocedural major bleeding (5/74; 6.8%) exhibited activity-to-antigen ratios <0.7, indicating subclinical VWF dysfunction. CONCLUSION Whereas clinically relevant VWF dysfunction is rare, loss of HMW VWF multimers is common in TAVI patients. Similar to surgery, TAVI leads to a restoration of this loss. Furthermore, VWF parameters may be useful parameter to evaluate risk of periprocedural bleeding.