Prognostic Impact of High-Molecular-Weight von Willebrand Factor Multimer Ratio in Classical Low-Flow Low-Gradient Aortic Stenosis.

INTRODUCTION: High-molecular-weight (HMW) von Willebrand factor (VWF) multimer deficiency occurs in classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) due to shear force-induced proteolysis. The prognostic value of HMW VWF multimer deficiency is unknown. Therefore, we sought to evaluate the impact of HMW VWF multimer deficiency on clinical outcome. METHODS: In this prospective research study, a total of 83 patients with classical LF/LG AS were included. All patients underwent dobutamine stress echocardiography to distinguish true-severe (TS) from pseudo-severe (PS) classical LF/LG AS. HMW VWF multimer ratio was calculated using densitometric Western blot band quantification. The primary endpoint was all-cause mortality. RESULTS: Mean age was 79 ± 9 years, and TS classical LF/LG AS was diagnosed in 73% (n = 61) and PS classical LF/LG AS in 27% (n = 22) of all patients. Forty-six patients underwent aortic valve replacement (AVR) and 37 were treated conservatively. During a mean follow-up of 27 ± 17 months, 47 deaths occurred. Major bleeding complications after AVR (10/46; 22%) were more common in patients with HMW VWF multimer ratio <1 (8/17; 47%) in comparison to patients with a normal multimer pattern (2/29; 7%) at baseline (p = 0.003). In a multivariable Cox regression analysis, HMW VWF multimer deficiency was a predictor of all-cause mortality (HR: 3.02 [95% CI: 1.31-6.96], p = 0.009) in the entire cohort. This association was driven by higher mortality rates in the AVR group (multivariable-adjusted HR: 9.4; 95% CI 2.0-43.4, p = 0.004). CONCLUSIONS: This is the first study to demonstrate the predictive value of HMW VWF multimer ratio for risk stratification in patients with classical LF/LG AS. HMW VWF multimer deficiency was associated with an increased risk of all-cause mortality and major bleeding complications after AVR.

Influence of pseudo-resistance on the effect of renal denervation on 24-hour ambulatory blood pressure levels.

BACKGROUND: Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, the negative result of the Symplicity HTN-3 trial led to a debate on the efficacy of RDN. METHODS: We systematically investigated the effects of RDN, evaluated by 24-hr ambulatory blood pressure measurements (ABPM), in a consecutive series of patients with resistant hypertension, which was defined by a mean office systolic blood pressure (SBP) >160 mm Hg (>150 mm Hg in patients with diabetes). Patients with a mean 24-hr SBP of less than 130 mm Hg at baseline were classified as pseudo-resistant, while all other patients were classified as true-resistant. After six months, we analyzed the response rates in true-resistant and in pseudo-resistant patients, respectively, by the means of 24-hr ABPM. Thereby, patients with a reduction of more than 5 mm Hg in 24-hr SBP were classified as responders. RESULTS: RDN was performed in 106 patients. By 24-hr ABPM, 20 patients (18.9%) were classified as pseudo-resistant patients. In this cohort, we only found two responders (response rate 10%) six months after RDN. By contrast, in true-resistant patients, the response rate was almost 60% and the mean BP reduction was -18.6/-9 mm Hg in 24-hr ABPM. CONCLUSIONS: We found a significant BP reduction in almost 60% of patients with true-resistant hypertension, but only in 10% in patients with pseudo-resistant hypertension. According to our results, patient selection seems to be crucial for acceptable response rates after RDN.

Transapical electrosurgical laceration and stabilization of mitral clips followed by transcatheter mitral valve replacement-A one-stop shop.

Objective: Electrosurgical laceration and stabilization of mitral clips (ELASTA-CLIP) is a bail-out technique to recreate a single-orifice mitral valve after transcatheter edge-to-edge repair (TEER) with subsequent transcatheter mitral valve replacement (TMVR). This technique is a novel option for patients with significant residual mitral regurgitation after TEER with high risk for conventional surgery. The original ELASTA CLIP procedure features a transseptal approach, whereas the TMVR with the Tendyne bioprosthesis has a transapical access. Hereby we tested the hypothesis that a modified transapical ELASTA CLIP technique can be safely applied transapically allowing a straightforward one-stop shop access strategy. Methods: We developed the procedural steps in a porcine passive-beating heart model and applied the modified technique with subsequent TMVR in 2 consecutive patients with severe mitral regurgitation after previous TEER. Patients were followed up to 30 days. Results: The modified transapical ELASTA CLIP procedure was successful in both patients. The mean total procedure time was 118 minutes, and the mean fluoroscopy duration 22 minutes. At 30 days' follow-up, both patients were alive without bleeding complications, reintervention, or prosthetic valve dysfunction. Conclusions: The modified transapical ELASTA CLIP procedure is technically feasible and safe at 30 days. Procedure times are lower compared with previous reports of the original transseptal approach.

Transcatheter, Transapical Mitral Valve Replacement After Mitral Valve Annuloplasty.

Mitral regurgitation (MR) recurrence after annuloplasty can lead to high-risk reoperations affecting long-term outcome. Transcatheter, transapical mitral valve replacement (TMVR) is an alternative method to treat severe MR without the use of cardiopulmonary bypass. This report describes the case of an 80-year old man who had undergone a mitral annuloplasty in 2006 and who now presented with severe recurrent MR. We performed TMVR using the Tendyne system (Abbott Laboratories). Our experience showed that TMVR after annuloplasty can be a safe method, thus reducing the procedural time and providing an alternative to the MitraClip (Abbott Laboratories) in-the-ring and the transcatheter aortic valve in-the-ring concept.

[Transcatheter mitral valve replacement : Indications, options, and techniques as well as important aspects for perioperative care]. / Interventioneller Mitralklappenersatz : Indikationen, Möglichkeiten und Technik sowie wichtige Aspekte für die perioperative Betreuung.

Transcatheter therapy of the mitral valve is more challenging compared to the aortic valve. Interventional therapy with the Mitra-Clip system, mimicking the surgical edge-to-edge repair, was first introduced in 2003 and received the CE mark in 2008. The first implantation of the Tendyne system, which is currently the only commercially available system for mitral valve replacement, was performed in 2014, and routine clinical use was approved in 2020. Several new valve platforms are in clinical development and will expand the treatment portfolio. This article will discuss the clinical indications, technical challenges and specific requirements for perioperative management.

First in Human: Transcatheter, Transapical Double Valve Replacement.

Transcatheter aortic valve replacement is a well-established therapy for severe aortic stenosis in patients with high surgical risk. Transcatheter mitral valve replacement just recently emerged as a novel modality to treat severe mitral regurgitation. We present the first case of a transcatheter, transapical native double valve replacement for severe aortic stenosis and mitral regurgitation. Our case shows that it is a safe and effective method, not requiring cardiopulmonary bypass and drastically reducing the procedural time. Therefore, patients with significant comorbidities that portend a high surgical risk with poor long-term outcome, may stand to benefit from this minimally invasive procedure.

Predictors of true-severe classical low-flow low-gradient aortic stenosis at resting echocardiography.

BACKGROUND: Classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) is subclassified into a true-severe (TS) and a pseudo-severe (PS) subform using low-dose dobutamine stress echocardiography (DSE). In clinical practice a resting peak jet velocity (Vmax) >3.5 m/s or a mean transvalvular gradient (MPG) >35 mmHg suggests the presence of TS classical LF/LG AS, but there is no data to support this. The aim of this study was therefore to investigate whether a resting Vmax >3.5 m/s or MPG >35 mmHg reliably predicted diagnosis of TS classical LF/LG AS. METHODS: One hundred (100) consecutive patients with classical LF/LG AS were prospectively recruited. All patients underwent DSE for subcategorization. The impact of Vmax and MPG for the presence of the TS subform were analyzed. RESULTS: TS classical LF/LG AS was diagnosed in 72 patients. Resting Vmax and resting MPG predicted true-severity with an ROC-AUC of 0.737 (95%CI: 0.635-0.838; p < 0.001) and 0.725 (95%CI: 0.615-0.834; p < 0.001), respectively. The optimal positive predictive values (PPV) for the diagnosis of TS classical LF/LG AS were obtained with a resting Vmax >3.5 m/s or resting MPG >35 mmHg. In a multivariate logistic regression analysis, Vmax >3.5 m/s was independently associated with a 5.33-fold odds-ratio of TS classical LF/LG AS (OR 5.33; 95%CI: 1.34-21.18, p = 0.018). CONCLUSIONS: TS classical LF/LG AS can be reliably predicted by a resting Vmax >3.5 m/s or a resting MPG >35 mmHg. Further imaging for subclassification is not needed in this situation.

Delayed Total Atrioventricular Block After Transcatheter Aortic Valve Replacement Assessed by Implantable Loop Recorders.

OBJECTIVES: The aims of this study were to evaluate the rate and time course of delayed total atrioventricular block (DT-AVB) after transcatheter aortic valve replacement (TAVR) using continuous electrocardiographic monitoring by implantable loop recorders and to identify potential predictors. BACKGROUND: DT-AVB has been defined as onset more than 2 days after TAVR or after hospital discharge and is reported in 10% to 15% of patients at 30-day follow-up. To date, there is no standardized diagnostic and therapeutic algorithm to manage TAVR patients at risk for DT-AVB. METHODS: Consecutive patients undergoing TAVR and simultaneous electrophysiologic testing without persistent or recurrent total atrioventricular block within 48 hours after the procedure underwent loop recorder implantation for full disclosure of atrioventricular conduction during 12-month follow-up. RESULTS: DT-AVB occurred in 7 of 59 patients (11.9%), with onset between 2 days and 3 months after the procedure. Both prolongation of the PQ interval between baseline and day 2 after TAVR (OR: 1.04; 95% CI: 1.01-1.09); P = 0.032) and prolongation of the HV interval during the procedure (OR: 1.07; 95% CI: 1.02-1.14; P = 0.015) significantly predicted the onset of DT-AVB. CONCLUSIONS: TAVR was associated with a considerable rate of DT-AVB of nearly 12% in this series. Prolongation of the PQ interval between baseline and day 2 and intraprocedural prolongation of the HV interval were significant predictors of DT-AVB.

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood. OBJECTIVE: The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing. METHODS: AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3). RESULTS: Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = -0.03, P = .762; and ρ = 0.15, P = .130, respectively). CONCLUSION: Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

2020 update of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGHTG) on the position statement of the ÖKG and ÖGHTG for transcatheter aortic valve implantation 2011.

This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGTHG) for transfemoral transcatheter aortic valve implantation.Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the ÖKG and the ÖGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.

High-molecular-weight von Willebrand Factor multimer ratio differentiates true-severe from pseudo-severe classical low-flow, low-gradient aortic stenosis.

AIMS: Upon high wall shear stress, high-molecular-weight (HMW) von Willebrand Factor (VWF) multimers are degraded, thus, HMW VWF multimer deficiency mirrors haemodynamics at the site of aortic stenosis (AS). The aim of the present study was to analyse the role of HMW VWF multimer ratio for subcategorization of classical low-flow, low-gradient (LF/LG) AS. METHODS AND RESULTS: Eighty-three patients with classical LF/LG AS were prospectively recruited and HMW VWF multimer pattern was analysed using a densitometric quantification of western blot bands. Patients were subclassified into true-severe (TS) and pseudo-severe (PS) classical LF/LG AS based on dobutamine stress echocardiography (DSE). Positive and negative predictive values (PPV/NPV) of HMW VWF multimer ratio for diagnosis of the TS subtype were calculated. HMW VWF multimer ratio in TS classical LF/LG AS was significantly decreased compared to PS classical LF/LG AS (0.86 ± 0.27 vs. 1.06 ± 0.09, P < 0.001). HMW VWF multimer deficiency occurred exclusively in the TS subtype with an optimal PPV of 1.000 and NPV of 0.379. HMW VWF multimer ratio showed a strong correlation with mean transvalvular pressure gradients during DSE (r = -0.616; P < 0.001). HMW VWF multimer ratio measured at baseline was higher compared to levels measured after DSE (0.87 ± 0.27 vs. 0.84 ± 0.31; P = 0.031) indicating DSE-induced increased proteolysis. CONCLUSION: HMW VWF multimer ratio represents a valuable biomarker for classical LF/LG AS subclassification and mirrors haemodynamics during DSE. HMW VWF multimer ratio identifies the TS subtype without the use of other imaging techniques.

In-stent restenosis in bare metal stents versus sirolimus-eluting stents after primary coronary intervention for acute myocardial infarction and subsequent transcoronary transplantation of autologous stem cells.

BACKGROUND: Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells. METHODS: Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography. RESULTS: We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES. CONCLUSIONS: Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC.

First Report of an Acute, Obstructive Thrombosis of a Melody Valve Used for Transcatheter Pulmonary Replacement.

Transcatheter pulmonary valve (TPV) replacement is an effective therapy of right ventricular outflow tract conduit dysfunction. Acute complications after TPV implantation include infective endocarditis, stent fracture, and device dislocation. We present a novel, life-threatening complication: an acute, noninfectious TPV thrombosis. Within 24 hours after implantation of a Melody system (Medtronic, Inc, Minneapolis, MN), the patient developed an acute TPV thrombosis characterized by severe TPV stenosis on echocardiography and contrast filling defects on computed tomography pulmonary angiography images. Genetic testing revealed heterozygous prothrombin G20210A polymorphism and homozygous 4G/4G polymorphism of the plasminogen-activator-inhibitor. The patient recovered after surgical valve replacement with a pulmonary homograft.

Impact of On-Site Cardiac Surgery on Clinical Outcomes After Transfemoral Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to investigate the outcome of high-risk and inoperable patients with severe symptomatic aortic stenosis undergoing transfemoral transcatheter aortic valve replacement (TAVR) in hospitals with (iOSCS) versus without institutional on-site cardiac surgery (no-iOSCS). BACKGROUND: Current guidelines recommend the use of TAVR only in institutions with a department for cardiac surgery on site. METHODS: In this analysis of the prospective multicenter Austrian TAVI registry, 1,822 consecutive high-risk patients with severe symptomatic aortic stenosis undergoing transfemoral TAVR were evaluated. A total of 290 (15.9%) underwent TAVR at no-iOSCS centers (no-iOSCS group), whereas the remaining 1,532 patients (84.1%) were treated in iOSCS centers (iOSCS group). RESULTS: Patients of the no-iOSCS group had a higher perioperative risk defined by the logistic EuroSCORE (20.9% vs. 14.2%; p < 0.001) compared with patients treated in hospitals with iOSCS. Procedural survival was 96.9% in no-iOSCS centers and 98.6% in iOSCS centers (p = 0.034), whereas 30-day survival was 93.1% versus 96.0% (p = 0.039) and 1-year survival was 80.9% versus 86.1% (p = 0.017), respectively. After propensity score matching for confounders procedural survival was 96.9% versus 98.6% (p = 0.162), 93.1% versus 93.8% (p = 0.719) at 30 days, and 80.9% versus 83.4% (p = 0.402) at 1 year. CONCLUSIONS: Patients undergoing transfemoral TAVR in hospitals without iOSCS had a significantly higher baseline risk profile. After propensity score matching short- and long-term mortality was similar between centers with and without iOSCS.

Acute Severe Mitral Stenosis Immediately After Transcatheter Aortic Valve Implantation.

An 86-year-old female patient was referred for treatment of symptomatic severe aortic stenosis. The heart team decided to perform transfemoral transcatheter aortic valve implantation. A 25 mm transcatheter aortic valve was implanted, but the valve migrated low into the left ventricular outflow tract. The subsequent removal and replacement procedures are described.

Rupture of the aortic root : A rare but life-threatening complication of transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has been shown to be a valid treatment option for patients with significant symptomatic aortic valve stenosis and high surgical risk. Rupture of the aortic root is a rare but life-threatening complication that occurs in approximately 1% of procedures and usually manifests as an acute complication at the time of valve implantation; however, physicians should be aware of a potentially subacute onset, since early recognition and immediate management are crucial. While many potential causes have been described, it is currently unknown which combinations will lead to its occurrence. Accurate preprocedural assessment of the aortic annulus and its adjacent structures as well as adequate sizing of the prosthetic valve are important steps to prevent rupture of the device landing zone.

Risk score for peri-interventional complications of carotid artery stenting.

BACKGROUND AND PURPOSE: Routinely available independent risk factors for the peri-interventional outcome of patients undergoing elective carotid artery stenting (CAS) are lacking. The rationale of the study was to create a risk score identifying high-risk patients. METHODS: We prospectively enrolled 606 consecutive patients assigned to CAS at a secondary care hospital. Various biochemical, clinical, and lesion-related risk factors were prospectively defined. The primary end point reflecting periprocedural complications encompassed minor and major stroke, nonfatal myocardial infarction and all-cause mortality within 30 days. RESULTS: Three percent of patients (n=18) experienced a nonfatal minor (n=13) or major (n=5) stroke. 1.3% of patients (n=8) died from fatal stroke (n=4) or other causes (n=4). No myocardial infarction was observed within 30 days after stenting. Multivariable analysis revealed diabetes mellitus with inadequate glycemic control (HbA1c > 7%), age > or = 80 years, ulceration of the carotid artery stenosis, and a contralateral stenosis > or = 50% as independent risk factors. A risk score formed with these variables showed a superior predictive value (C-statistic = 0.73) compared with single risk factors. The presence of 2 or more of these risk factors identified patients with a risk of 11% for a periprocedural complication compared with 2% in patients with a score of 0 or 1. CONCLUSIONS: In patients undergoing elective CAS, a risk score based on routinely accessible variables was able to identify patients at high-risk for atherothrombotic events and all-cause death within 30 days after the intervention.

Late renal artery stenosis after percutaneous renal denervation.

: Renal denervation has been adopted as an additional treatment option to pharmacological antihypertensive therapy in patients with resistant hypertension. However, concerns have been raised with regard to the possible occurrence of renal artery stenosis.Our patient developed renal artery stenosis late after renal denervation, as magnetic resonance angiography 6 months after the procedure had showed no stenosis.Invasive reangiography, which revealed the stenosis, was performed due to recurrent resistant hypertension 28 months after renal denervation. Review of the saved loops of the denervation procedure showed that the stenosis was located near the most proximal ablation point.

Implantation depth measured by 64-slice computed tomography is associated with permanent pacemaker requirement following transcatheter aortic valve implantation with the Core Valve(®) system.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) are at increased risk for post-interventional conduction disturbances leading to pacemaker (PM) implantation. We analyzed the association between implantation depth within the left ventricular outflow tract (LVOT), measured by 64-slice computed tomography (CT), and 'index electrocardiographic (ECG) changes' (new onset atrioventricular-block grade II or III or left bundle branch block with PR interval prolongation >200ms). METHODS: We evaluated patients who underwent TAVI with the Core Valve(®) revalving system (Medtronic, Minneapolis, MN, USA) for treatment of severe aortic stenosis at our department. Patients with a prior PM implantation and patients for whom no CT scan was available after 3 months were excluded from analysis. We assessed implantation depth of the prosthesis within the LVOT as possible risk factors for the development of post-interventional 'index ECG changes' resulting in PM implantation and compared it with individual patient data as well as echocardiographic and electrocardiographic parameters. RESULTS: The final study cohort comprised 53 patients for whom a 64-slice CT scan was available (mean age 81.7±5.1 years, 36% male). Twenty-eight of these finally underwent PM implantation due to 'index ECG changes' within the first 48hours after TAVI. Univariate logistic regression analysis could identify implantation depth of the prosthesis as the only significantly correlated risk factor for PM need in our cohort (OR 1.27, 95% CI: 1.08-1.51, p=0.004). A cut-off value of 6mm predicted this need with a sensitivity of 89% and specificity of 40%. CONCLUSION: Implantation depth of the Core Valve(®) into the LVOT was associated with post-procedural PM requirement. Thereby, a cut-off value of 6mm, as measured by 64-slice CT, proved useful to define patients at risk for PM requirement.