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Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias.

We compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex. A Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population. Persons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40-3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI. Both persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45-54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.

ObjectivesTranscatheter aortic valve implantation (TAVI) is performed in elderly patients with severe aortic valve stenosis and increased operative risks. We tested the hypothesis that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have a predictive value for prevalent complications after TAVI and could serve as indicators of systemic inflammation in the early postoperative period.DesignProspective observational study.SettingThis study is a secondary analysis of multicentre CESARO- study.Participants48 patients with TAVI were included and 43 obtained the complete assessment.Primary and secondary outcome measuresPatients’ clinical parameters, demographic data, peripheral AChE and BChE activities and routine blood markers were assessed throughout the perioperative period using bedside point-of-care measurements for AChE and BChE. Postoperative complication screening was conducted up to the third postoperative day and included infections, delirium and heart-rhythm disturbances. After assessment, the patients were divided into complication and noncomplication group.ResultsOf 43 patients, 24 developed postsurgical complications (55.8%). Preoperative assessment showed no significant differences regarding demographic data and laboratory markers, but preoperative BChE levels were significantly lower in patients who developed postoperative complications (complication group 2589.2±556.4 vs noncomplication group 3295.7±628.0, Cohen’s r=0.514, p<0.001). In complication group, we observed an early, sustained reduction in BChE activity from preoperative to postoperative period. In complication group, BChE levels were significantly lower at each time point compared with noncomplication group. AChE activity showed no significant difference between both groups. Complication group also had longer stay in hospital overall.ConclusionBChE could be a useful perioperative biomarker to identify patients with a higher risk for postoperative complications after TAVI. By using point-of-care measurements, the levels of BChE are fast available and can lead to an early targeted therapy. Predicting the length of the hospital stay might play an important role in staff and resource management for these patients.Trial registration numberNCT01964274; Post-results.

Background Transcatheter aortic valve replacement has become a routine procedure for patients with severe symptomatic aortic stenosis at increased surgical risk. Not much is known about using prophylactic support with venoarterial extracorporeal membrane oxygenation in patients undergoing transcatheter aortic valve replacement and eventually concomitant complex percutaneous coronary intervention. Case presentation We present a successful procedure of transcatheter aortic valve replacement and high-risk percutaneous coronary intervention utilizing venoarterial extracorporeal membrane oxygenation for hemodynamic support in a very frail 88-year-old Caucasian woman with severe symptomatic aortic stenosis and coronary bypass grafting in the past. Echocardiography revealed a “low-flow low-gradient” aortic stenosis (mean transvalvular gradient 30 mmHg, aortic valve area 0.4 cm 2 , significant calcification), a left ventricular ejection fraction of 35%, severe mitral regurgitation with moderate stenosis (mean transvalvular gradient 7 mmHg), with a systolic pulmonary artery pressure of 80 mmHg. Moreover, pre-interventional coronary angiography exposed a severe left main ostial stenosis and sequential subtotal heavily calcified stenosis of the left anterior descending artery . Computed tomographic angiography showed no heavy tortuosity but moderate calcification of the iliofemoral arteries. The procedure was performed under general anesthesia in our hybrid operating room. Extracorporeal membrane oxygenation was established by left femoral percutaneous cannulation using a 21-Fr venous and 15-Fr arterial cannula. Subsequently, complex percutaneous coronary intervention with implantation of two drug-eluting stents from the left main into the left anterior descending artery was performed via a right femoral arterial 7F sheath. Thereafter, a 23-mm Sapien 3 aortic valve prosthesis (Edwards, Irvine, CA, USA) was implanted via right femoral artery in the usual manner, whereby the arterial pigtail catheter for marking the aortic annulus during transcatheter aortic valve replacement was inserted over a Check-Flo® Hemostasis Assembly (Cook Medical, Bloomington, IN, USA) on a Y-adapter via the arterial extracorporeal membrane oxygenation cannula. After extracorporeal membrane oxygenation decannulation, vascular closure was easily performed using the MANTA vascular closure device in order to reduce procedural time and risk of access site complications. Conclusions In summary, we demonstrate the feasibility of elective prophylactic extracorporeal membrane oxygenation implementation in selected very high-risk and frail patients undergoing transcatheter aortic valve replacement and percutaneous coronary intervention in order to avoid intraprocedural complications.

BackgroundAortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI).Methods143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (Pmean), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA).ResultsAVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67–0.86) vs. 0.83 (IQR 0.74–0.93), p < 0.05] and in patients with BAV compared to TAV [0.70 (IQR 0.63–0.78) vs. 0.81 (IQR 0.71–0.89), p < 0.05]. Normalization of vWF:Ac/Ag ratio was achieved in 61% patients 24 h after TAVI. As in the overall study cohort, vWF:Ac/Ag ratio increased significantly in all severe AS subgroups 6 h after TAVI (each p < 0.05). Regarding binary logistic regression analysis, BAV was the only significant predictor for AVWS.ConclusionsBAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology.

Background: The primary objective of this study was to evaluate the initial experience in Germany with the Meril Myval™ (MM) transcatheter heart valve (THV) system for the treatment of severe symptomatic aortic valve stenosis. The MM THV is a novel balloon-expandable valve with an expanded sizing matrix. Contemporary patients undergoing TAVI with the established Edwards Sapien™ (ES) THV served as the comparator group. Methods: Between 1st March and 31 August 2020 a total of 134 patients (33% female, 80.1 ± 6.7 years; EuroScore II 4.7 ± 4.8) underwent TAVI with an MM (95% transfemoral) for severe aortic stenosis at six German tertiary care centers. Results: Correct positioning of the THV was achieved in 98.5% (n = 132). Mean aortic gradients (MPG) were reduced from 42 ± 14 mmHg to 11 ± 5 mmHg. Mild postprocedural paravalvular leak (PVL) was observed in 62% (n = 82) patients, whereas only one patient had more than mild PVL. New permanent pacemaker implantation (PPI) was indicated in 15 patients (11%). Major vascular complications occurred in 6.7% (n = 9) patients. The in-hospital combined incidence of all-cause death and stroke was 4.5% (n = 6). In the comparator group that included 268 patients, the 30-day incidences of PPI, major vascular complications, and the composite of all-cause death and stroke were 16%, 1.9%, and 7.1%, respectively; MPGs were reduced from 44 ± 15 mmHg to 12.8 ± 4.6 mmHg and the more than mild PVL occurred in 0.7%. Conclusions: The MM is a promising novel THV system, with performance comparable to the established ES THVs. These findings await confirmation by ongoing randomized trials.

BackgroundThis study investigated the impact of prophylactic veno-arterial extracorporeal membrane oxygenation (pECMO) in patients with depressed left ventricular ejection fraction (dLVEF) undergoing transcatheter aortic valve implantation (TAVI).MethodsOut of 1490 patients undergoing TAVI at two centers (2010–2015), 222 patients had dLVEF (≤ 40%). Of these, 21 patients (10%) underwent TAVI with pECMO. Complications and outcome according to pECMO were analyzed in the entire and in a propensity-matched population.ResultsIn the entire population, patients with pECMO had a higher logEuroScore I (33% ± 19 vs. 25% ± 17; p = 0.037), worse LVEF (26% ± 7 vs. 32% ± 7; p = 0.001), more major bleedings (29% vs. 9%; p = 0.015), higher transfusion rate (30% vs. 10%; p = 0.019) and longer in-hospital stay (9.0 [7.0;14.0] vs. 7.0 [5.0;10.0] days; p = 0.024). After propensity matching only transfusion rate remained higher with pECMO (30% vs. 7%; p = 0.025). In the entire population, rate and risk of 30-day mortality was higher with pECMO (24% vs. 6%, HR 95%CI 4.29 [1.51–12.19]; p = 0.006). In the matched population, this effect was attenuated (24% vs. 12%, HR 95%CI 2.09 [0.61–7.23]; p = 0.243). Cumulative rate and risk of 1-year mortality did not differ in the entire (log-rank p = 0.069; 39% vs. 22%, HR 95%CI 1.99 [0.94–4.24]; p = 0.074) nor in the matched population (log-rank p = 0.520; 39% vs. 31%, HR 95%CI 1.34 [0.55–3.28]; p = 0.523).ConclusionIn patients with dLVEF undergoing TAVI, periprocedural pECMO support does not seem to improve patient outcome.

ObjectivesThis study was performed to analyse anaesthesia-related complications and side effects in patients undergoing transcatheter aortic valve implantation (TAVI) under general anaesthesia.DesignRetrospective study.SettingThe study was performed as a single-centre study in a hospital of tertiary care in Germany.ParticipantsAll 853 patients, who underwent TAVI at the Universitätsklinikum Regensburg between January 2009 and July 2015, were included. 52.5% were female patients.Primary and secondary outcome measuresWe gathered information, such as recent illness, vital parameters and medication administered during the intervention and postoperatively for 12 hours. We analysed all anaesthesia-related complications and anaesthesia-related side effects that occurred during the intervention and entire hospital stay.ResultsWe analysed all 853 TAVI procedures. The mean patient age was 79 ± 6 years. In 99.5% of cases, we used volatile-based anaesthesia. 2.8% (n=24; transfemoral (TF): n=19 [3.8%]; transapical (TA): n=5 [1.4%]) of all cases suffered from anaesthesia-related complications. 819 (TF: n=447; TA: n=372) anaesthesia-related side effects occurred in 586 (68.7%, TF: n=325 [64.2%], TA: n=261 [75.2%]) patients. Neither the complications nor the side effects had any serious consequences. Intraoperative hypothermia in 44% of cases (TF: n=202 [39.9%]; TA: n=173 [49.9%]) and postoperative nausea and vomiting in 27% (n=232; TF: n=131 [25.9%], TA: n=101 [29.1%]) of cases were the most common anaesthesia-related side effects.ConclusionIn this study, serious anaesthesia-related complications were rarely seen, and non-critical anaesthesia-related side effects could have been avoided through consistent prophylaxis and management. Therefore, despite their high anaesthetic risk, general anaesthesia is justifiable in patients who underwent TAVI.