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Lead-free hybrid perovskites have attracted significant attention due to the toxicity of lead and poor stability of lead hybrid perovskites. Among them, bismuth-based hybrid perovskites are currently being developed as they possess negligible toxicity, moderate price and great stability. Herein, we report the synthesis of two stable organic–inorganic perovskites based on one-dimensional iodobismuthates and the benzimidazolium cation (BzlmH)+. Firstly, the BzImH[BiI]4·H2O structure (IEF-4 RT-phase) was prepared using a simple and fast synthetic method at room temperature, leading to the dehydrated BzImH[BiI]4 (IEF-4 HT-phase) upon the removal of water by soft heating. This dehydration-hydration process, which has never been reported for Bi-based perovskites, is fully reversible, affecting the optoelectronic properties of the solid, with an optical bandgap of ∼2 eV. Furthermore, this perovskite material formed stable and homogeneous thin films, which exhibited a high absorption coefficient (1.5 × 105 cm−1) comparable to that of the CH3NH3PbI3 lead perovskite. Thus, both the optoelectronic properties and air stability of these perovskites make them suitable as absorber materials in solar cells. [ABSTRACT FROM AUTHOR]

Background: Postpubertal women with inherited long QT syndrome type 2 (LQT2) are at increased risk for polymorphic ventricular tachycardia (pVT) and sudden cardiac death (SCD), particularly during the postpartum period.Objective: To investigate whether sex hormones directly modulate the arrhythmogenic risk in LQTS.Methods: Prepubertal ovariectomized transgenic LQT2 rabbits were treated with estradiol (EST), progesterone (PROG), dihydrotestosterone (DHT), or placebo (OVX).Results: During 8 weeks of treatment, major cardiac events-spontaneous pVT or SCD-occurred in 5 of the 7 EST rabbits and in 2 of the 9 OVX rabbits (P <.05); in contrast, no events occurred in 9 PROG rabbits and 6 DHT rabbits (P <.01 vs PROG; P <.05 vs DHT). Moreover, EST increased the incidence of pVT (P <.05 vs OVX), while PROG reduced premature ventricular contractions, bigeminy, couplets, triplets, and pVT (P <.01 vs OVX; P <.001 vs EST). In vivo electrocardiographic monitoring, in vivo electrophysiological studies, and ex vivo optical mapping studies revealed that EST promoted SCD by steepening the QT/RR slope (P <.05), by prolonging cardiac refractoriness (P <.05), and by altering the spatial pattern of action potential duration dispersion. Isoproterenol-induced Ca(2+) oscillations resulted in early afterdepolarizations in EST-treated hearts (4 of 4), while PROG prevented SCD by eliminating this early afterdepolarization formation in 4 of the 7 hearts (P = .058 vs EST; P <.05 vs OVX). Analyses of ion currents demonstrated that EST increased the density of I(Ca,L) as compared with OVX (P <.05) while PROG decreased it (P <.05).Conclusion: This study reveals the proarrhythmic effect of EST and the antiarrhythmic effect of PROG in LQT2 in vivo, outlining a new potential antiarrhythmic therapy for LQTS. [ABSTRACT FROM AUTHOR]

The study was designed to assess the beat-to-beat variation of ventricular repolarization in patients with myocardial ischemia, hear failure, and in normal subjects. Autonomic tone may alter the dynamic QT/RR interval relation and thus may be involved in ventricular arrhythmia development, especially in the diseased heart. The study included 145 patients (age 16-86 years) with CHF (LVEF < or = 0.30) or unstable angina pectoris (LVEF > 0.60). The control group consisted of healthy volunteers giving physiological baseline measures for the evaluated parameters: cycle length, QT interval, and QT/RR interval ratio during three time periods. In patients with myocardial ischemia (LVEF > 0.60) and healthy subjects the QT/RR interval ratio did not reveal significant differences between both groups (QT/RR(CAD) = 0.36 +/- 0.77 vs QT/RR(controls) = 0.28 +/- 0.83; NS). In sharp contrast, in patients with severe heart failure, RR dependent instantaneous variation of the QT interval was almost missing and regression line analysis disclosed a QT/RR interval slope substantially enhanced by 196% (compared to normal subjects) and 131% (compared to CAD patients; P < 0.05) with a complete loss of circadian modulation (QT/RR(CHF) = 0.83 +/- 0.71 vs QT/RR(CAD) = 0.36 +/- 0.77 vs QT/RR(controls) = 0.28 +/- 0.83; P < 0.05). Beat-to-beat QT interval assessment provides a dynamic parameter of physiological and altered repolarization in defined study groups. Compared to other groups (preserved LVEF), patients with left ventricular impairment exhibited a significantly increased sensitivity of repolarization to cycle length (enhanced QT/RR interval ratio) and a blunted circadian modulation of the QT interval. This is consistent with concept that increased repolarization disparity may be deleterious being a potential pathophysiological basis for enhanced arrhythmic risk. [ABSTRACT FROM AUTHOR]

Arterial hypertension frequently occurs in association with myocardial ischaemia and is an independent and significant risk factor for the development of coronary artery disease (CAD), as is left ventricular hypertrophy due to arterial hypertension. The prevalence of CAD in patients with hypertension is high, while hypertension occurs in approximately 60%of patients with CAD. Myocardial ischaemia occurs both in the presence and absence of CAD, probably as the result of limitation of coronary vasodilator capacity and reduction in coronary flow. This may occur in hypertension due to increased transmural coronary artery resistance, alterations in the vascular wall and endothelial dysfunction. Furthermore, left ventricular hypertrophy itself predisposes the heart towards ischaemia due to an increased diffusion distance between capillaries.When myocardial ischaemia occurs in hypertensive patients, 90% of all episodes are aysmptomatic. The highest incidence of ischaemic episodes appears to occur in treated elderly hypertensive men with inadequate blood pressure control (40%).Calcium antagonists exert a range of beneficial effects in hypertensive patients, including reduction of blood pressure, improvement in myocardial blood flow, regression of left ventricular hypertrophy and cardioprotection in reper-fused organs. However, while vasoprotective effects have been demonstrated in animal models, beneficial effects in man are uncertain. Thus, in established coronary atherosclerosis, calcium antagonist treatment has produced only a mild reduction in the appearance of new atherosclerotic lesions. (Eur Heart J 1996; 17 (Suppl G): 20–24) [ABSTRACT FROM PUBLISHER]

In a multicentre study efficacy and safety of propafenone 450 mg day−1 and 750 mg day−1 was studied in 97 patients with frequent ventricular premature beats (VPB > 30 h−1). 70 patients suffered from organic heart disease, in 27 patients no organic heart disease was present during an initial work-up. After a 1-week washout period, all patients underwent 24 h Holter monitoring. Patients were then treated by propafenone 450 mg day−1 and controlled for 24 h Holter, ECG, blood pressure, blood chemistry and side-effects afrer 1 week of treatment. At this time, 35 patients were responders (reduction of VPB > 84%, of ventricular pairs > 90% and of ventricular tachycardia 100%). The mean reduction of VPB in all patients was 60%, of ventricular pairs 88% and of ventricular tachycardia 100%. When treatment was continued for 3 weeks 20/35 patients (56%) were still responders. The mean reduction of VPB was 83%. In 42 non-responders to 450 mg day−1 the dose was increased to 750 mg day−1. Of these patients, 17 (41%) became responders after 3 weeks of treatment; the mean reduction of VPB increased from 17% (first week, 450 mg day−1) to 63% (750 mg day−1). Ventricular pairs were reduced by 80%, ventricular tachycardia by 100%. Side-effects occurred in 11/97 patients and limited therapy in six patients. The most frequent complaints were dryness of the mouth, nausea, tiredness, headache and gastrointestinal upset. In conclusion, propafenone in a dose of 450–750 mg day−1 seems to be an effective andsafe antiarrhythmic agent in the majority of patients. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To determine the diagnostic and prognostic impact of abnormal Q waves in comparison to or in combination with ST segment abnormalities in the right precordial and inferior leads as indicators of right ventricular infarction during the acute phase of inferior myocardial infarction. DESIGN--Prospective study of a consecutive series of 200 patients with acute inferior myocardial infarction with and without right ventricular infarction. SETTING--Department of internal medicine, university clinic. RESULTS--Right ventricular infarction was diagnosed in 106 (57%) out of 187 patients from the results of coronary angiography, technetium pyrophosphate scanning, and measurement of haemodynamic variables or at necropsy, or both. In the acute phase of inferior infarction ST segment elevation > or = 0.1 mV in any of the right precordial leads V4-6R was the most reliable criterion for right ventricular infarction (sensitivity, 89%; specificity, 83%). Abnormal Q waves in the right precordial leads, the most specific criterion (91%) for right ventricular infarction, were superior to ST segment elevation in patients admitted > 12 hours after the onset of symptoms. Both ST segment elevation in leads V4-6R (increase in in hospital mortality, 6.2-times; P < 0.001; major complications, 2.3-times; P < 0.01) and abnormal Q waves (2.3-times, P < 0.05; 1.8-times, P < 0.05) on admission were highly predictive of a worse outcome during the in hospital period. In the presence of inferior myocardial infarction previously proposed combined electrocardiographic criteria were not better diagnostically or prognostically than ST segment abnormalities and abnormal Q waves alone. CONCLUSIONS--During the first 24 hours of inferior myocardial infarction ST segment elevation and abnormal Q waves derived from the right precordial leads are complementary rather than competitive criteria for reliably diagnosing right ventricular infarction, both indicating a worse in hospital course for the patient. In this they are better than any other previously proposed combined electrocardiographic criteria in diagnosing right ventricular infarction. Right precordial leads should be routinely monitored in acute inferior myocardial infarction. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To assess the clinical criteria predicting the short and long-term efficacy of propafenone, an agent with class IC antiarrhythmic activity and a broad pharmacological profile. DESIGNS--Prospective study of propafenone at doses of 450 to 900 mg/day during a six week dose titration period (including a placebo phase with two separate 24 Holter recordings). Responders to treatment were followed for one year. PATIENTS--One hundred patients with frequent ventricular arrhythmias (greater than 30 extrasystoles/h) of Lown class III and IVA/B and without evidence of myocardial infarction within the past six months. ANALYSIS--Multivariate regression analysis of spontaneous arrhythmia variability and of different clinical variables to determine the short and long-term efficacy and safety of propafenone. MEASUREMENTS AND MAIN RESULTS--Propafenone 450 mg/day was effective in 30/100 patients (30%), and at 600 mg/day another 14 responded. The efficacy of propafenone correlated with a low spontaneous arrhythmia variability and, as shown by multivariate analysis, with a lower patient age (p less than 0.05). When the dose was increased to 900 mg/day a further six (12%) patients responded. However, with increasing doses of propafenone, the one year probability of effective treatment decreased from 86% (450 mg/day) to 67% (600 mg/day) and to 44% (900 mg/day). After restudying the patients at three, six, and 12 months and after dose adjustment in 11/44 patients (25%), 31 patients (70%) remained responders. Loss of permanent antiarrhythmic efficacy was best predicted by the initial dose that achieved a response. No patient died suddenly or had arrhythmogenic effects during Holter monitoring. Side effects occurred in 36% of patients but these rarely limited long-term treatment. CONCLUSIONS--A younger age, low spontaneous arrhythmia variability, and particularly a low titration dose were the best predictors of the short and long term efficacy of propafenone. All other responders should have repeated Holter recordings during the first year of treatment. [ABSTRACT FROM PUBLISHER]

The introduction of programmed electrical stimulation of the heart opened up new ways for the diagnosis and treatment of recurrent tachycardias. Programmed stimulation not only allows study of the site of origin and mechanisms of arrhythmias, but also the evaluation of the modes of reproducible initiation and termination of tachycardia and the study of effects of drugs on the tachycardia mechanisms. By analyzing results of invasive and non-invasive programmed stimulation, the most successful pacing modality to reproducibly terminate tachycardia can be identified, but complications of pacing can also be recognized (such as the initiation of other arrhythmias). Careful consideration of the results of programmed electrical stimulation is necessary to select the best implantable unit for a particular patient, and to design or redesign new or already implanted antitachycardia units. [ABSTRACT FROM PUBLISHER]

The safety and efficacy of adding oral carvedilol (25 mg twice daily) to standardized treatment of unstable angina was assessed in a multicenter, randomized, double-blind, placebo- controlled trial on 116 patients with acute unstable angina. Patients were monitored in an intensive care unit and underwent 48-hour Holter monitoring to assess transient ischemia. Carvedilol as adjunctive therapy resulted in a significant reduction of median heart rate (65 vs 75 beats/min, p <0.05), mean systolic blood pressure (133 vs 130 mm Hg, p <0.05), and mean rate-pressure product (8,337 vs 10,042, p <0.05). Carvedilol reduced the ischemic burden during 48 hours of treatment by 75% (49 vs 204 minutes), including a 36% reduction of patients with ischemic episodes (p <0.05), a 66% reduction of the mean number of ischemic episodes (8 vs 24, p <0.05), and a 76% reduction in the mean duration of ischemic episodes (50 vs 205 minutes, p <0.05). Side effects occurred in 8 of 59 patients (13.6%) in the carvedilol group and in 5 of 54 patients (8.8%) given placebo. Although not significant, the early onset of maximal blood pressure reduction and the delayed effect on heart rate were closely correlated to drug-induced hypotension and bradycardia in the carvedilol group. Thus, carvedilol as an adjunctive to standardized treatment effectively reduces heart rate and blood pressure, and thus the ischemic burden in patients with unstable angina pectoris, but requires close monitoring of patients at risk for bradycardia or hypotension. [ABSTRACT FROM AUTHOR]

Long QT syndrome (LQTS) is a congenital arrhythmogenic channelopathy characterized by impaired cardiac repolarization. Increasing evidence supports the notion that LQTS is not purely an “electrical” disease but rather an “electro-mechanical” disease with regionally heterogeneously impaired electrical and mechanical cardiac function. In the first part, this article reviews current knowledge on electro-mechanical (dys)function in LQTS, clinical consequences of the observed electro-mechanical dysfunction, and potential underlying mechanisms. Since several novel imaging techniques – Strain Echocardiography (SE) and Magnetic Resonance Tissue Phase Mapping (TPM) – are applied in clinical and experimental settings to assess the (regional) mechanical function, advantages of these non-invasive techniques and their feasibility in the clinical routine are particularly highlighted. The second part provides novel insights into sex differences and sex hormone effects on electro-mechanical cardiac function in a transgenic LQT2 rabbit model. Here we demonstrate that female LQT2 rabbits exhibit a prolonged time to diastolic peak – as marker for contraction duration and early relaxation – compared to males. Chronic estradiol-treatment enhances these differences in time to diastolic peak even more and additionally increases the risk for ventricular arrhythmia. Importantly, time to diastolic peak is particularly prolonged in rabbits exhibiting ventricular arrhythmia – regardless of hormone treatment – contrasting with a lack of differences in QT duration between symptomatic and asymptomatic LQT2 rabbits. This indicates the potential added value of the assessment of mechanical dysfunction in future risk stratification of LQTS patients. [ABSTRACT FROM AUTHOR]

Background: Despite the known effects of drug-eluting stents (DES), other cofactors attributed to patient characteristics affect their success. Interest focused on designing a study minimizing these factors to answer continuing concerns on the heterogeneity of response to different DESs. The study's aim was to investigate the feasibility and impact of an intra-individual comparison design in patients (pts) with two coronary artery stenosis treated with a Sirolimus- (SES) and a Paclitaxel- (PES) eluting stent. Methods and results: The study was conducted as a prospective, randomized, multi-center trial in 112 pts who consented to treatment with a SES and a PES. Pts were eligible if they suffered from the presence of two single primary target lesions in two different native coronary arteries. Lesions were randomized to either SES or PES treatment. The primary endpoint was in-stent luminal late loss (LLL), as determined by quantitative angiography at 8months; clinical follow up was obtained at 1, 8, and 12months additionally. The LLL (0.13±0.28mm SES vs. 0.26±0.35mm PES, p=0.011) showed less neointima in SES. With a predefined cut-off criterion of 0.2mm difference in LLL, 53/87 pts SES and PES were similar effective. 34/87 pts had a divergent result, 26 pts had greater benefit from SES while 8 pts had greater benefit from PES. Overall, MACE (MI, TLR, and death) occurred in 19 (17%) pts. Based on lesion analysis of 108 lesions treated with SES and 110 lesions treated with PES, 5 (4.6%) lesions with SES and 3 (2.7%) lesions with PES required repeated TLR. Conclusion: An intra-individual comparison design to assess differences in efficacy of different DESs is feasible, safe and achieves similar results to inter-individual studies. This study is among the first to show that failure of one DES does not necessarily implicate failure of another DES and vice versa. [ABSTRACT FROM AUTHOR]

Aims: Short QT syndrome type 1 (SQT1) is a genetic channelopathy caused by gain-of-function variants in human-ether-a-go-go (HERG) underlying the rapid delayed-rectifier K+ current (IKr), leading to QT-shortening, ventricular arrhythmias, and sudden cardiac death. Data on efficient pharmacotherapy for SQT1 are scarce. In patients with primary carnitine-deficiency, acquired-short QT syndrome (SQTS) has been observed and rescued by carnitine supplementation. Here, we assessed whether carnitine exerts direct beneficial (prolonging) effects on cardiac repolarization in genetic SQTS., Methods and Results: Adult wild-type (WT) and transgenic SQT1 rabbits (HERG-N588K, gain of IKr) were used. In vivo electrocardiograms (ECGs), ex vivo monophasic action potentials (APs) in Langendorff-perfused hearts, and cellular ventricular APs and ion currents were assessed at baseline and during L-Carnitine/C16-Carnitine-perfusion. Two-dimensional computer simulations were performed to assess re-entry-based ventricular tachycardia-inducibility. L-Carnitine/C16-Carnitine prolonged QT-intervals in WT and SQT1, leading to QT-normalization in SQT1. Similarly, monophasic and cellular AP duration (APD) was prolonged by L-Carnitine/C16-Carnitine in WT and SQT1. As underlying mechanisms, we identified acute effects on the main repolarizing ion currents: IKr-steady, which is pathologically increased in SQT1, was reduced by L-Carnitine/C16-Carnitine and deactivation kinetics were accelerated. Moreover, L-Carnitine/C16-Carnitine decreased IKs-steady and IK1. In silico modelling identified IKr changes as the main factor for L-Carnitine/C16-Carnitine-induced APD-prolongation. 2D simulations revealed increased sustained re-entry-based arrhythmia formation in SQT1 compared to WT, which was decreased to the WT-level when adding carnitine-induced ion current changes., Conclusion: L-Carnitine/C16-Carnitine prolong/normalize QT and whole-heart/cellular APD in SQT1 rabbits. These beneficial effects are mediated by acute effects on IKr. L-Carnitine may serve as a potential future QT-normalizing, anti-arrhythmic therapy in SQT1., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy., Methods: KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes., Results: KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P < .0001, LQT1-SupRep vs. WT, P = ns). Under β-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour., Conclusions: This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: A variety of health-related mobile applications (apps) and wearables often encompass a narrow application area. Our study therefore aims to provide the basis for the development of an app that comprehensively assists patients to deal with their disease in the best possible way and that improves the course of the disease in the long term., Methods: We conducted a multicenter analysis of patients using a questionnaire study at two German clinics and surveyed 100 patients with cardiovascular disease. For the analysis of the interviews, particularly Likert scales were used., Results: 24.0% were female, median age was 62.5 years. Leading causes for hospitalization were coronary artery disease (40.0%) and heart failure (22.0%). The most frequent pre-existing conditions were arterial hypertension (55.0%), atrial fibrillation or atrial flutter (31.0%), and again coronary artery disease (31.0%). Typical disease associated feelings were fear for life (43.0%) and uncertainty (43.0%). When considering future management of the disease, 75.0% felt motivated, 70.0% felt confident, and 68.0% felt hopeful. Of the patients surveyed, 60.0% indicated a willingness to use the app and another 24.0% were potentially willing to do so. Furthermore, significantly more patients < 63 years stated a willingness or potential willingness to use the app (p = 0.029). For those considering an app usage in general, the most favoured features were a document management (81.8%) and a medication management (65.9%). While only 36.4% indicated that the app could at least partially alleviate their worries, 94.3% expected a reduction in organizational effort. With respect to age groups, there was no significant difference (organizational effort: p = 0.239; worries: p = 0.275)., Conclusions: Particularly younger patients < 63 years with cardiovascular disease show a substantial willingness to use an app as a special health support, particularly in terms of document and medication management. They especially hope for a reduction in organizational effort., (© 2024. The Author(s).)

Electromechanical reciprocity - comprising electro-mechanical (EMC) and mechano-electric coupling (MEC) - provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions - such as (drug-induced) acquired long QT syndrome (aLQTS) - might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC in vivo, we used tissue phase mapping cardiac MRI and a 24-lead ECG vest in healthy (control) and I Kr -blocker E-4031-induced aLQTS rabbit hearts. MEC was studied in vivo by acutely increasing cardiac preload, and ex vivo by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT-interval, RTn370) was prolonged compared to control (P < 0.0001) with increased spatial and temporal RT heterogeneity (P < 0.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico-basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (P < 0.0001). Additionally, regional RT-dispersion increased in aLQTS. Motion-correction allowed us to determine APD-prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload-changes prevented a clear analysis of MEC ex vivo. Mechano-induced RT-prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT-related arrhythmogenesis, warranting further mechanistic investigations. KEY POINTS: Electromechanical reciprocity comprising excitation-contraction coupling (EMC) and mechano-electric feedback loops (MEC) is essential for physiological cardiac function. Alterations in electrical and/or mechanical heterogeneity are known to have potentially pro-arrhythmic effects. In this study, we aimed to investigate how electrical changes impact on the mechanical function (EMC) and vice versa (MEC) both under physiological conditions (control) and in acquired long QT syndrome (aLQTS). We show that changing the electrical function (in aLQTS) results in significantly altered mechanical heterogeneity via EMC and, vice versa, that increasing the preload acutely prolongs repolarization duration and increases electrical heterogeneity, particularly in aLQTS as compared to control. Our results substantiate the hypothesis that LQTS is an ‛electro-mechanical', rather than a 'purely electrical', disease and suggest that acute MEC effects may play an additional role in LQT-related arrhythmogenesis., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: In transcatheter aortic valve replacement (TAVR), complications may force the need for a surgical bailout, but knowledge is rare about outcomes in Germany., Methods: Using national health records, we investigated all TAVR in German hospitals between 2007 and 2020, focusing on 2018-2020. We extracted data on those interventions with need for a surgical bailout., Results: A total of 159,643 TAVR were analyzed, with an overall rate of surgical bailout of 2.30 %, an overall in-hospital mortality of 3.85 %, and in-hospital mortality in case of bailout of 16.51 %. The number of all annual TAVR procedures increased substantially (202 to 22,972), with the rate of surgical bailout declining from 27.23 to 0.61 % and overall mortality from 11.39 to 2.29 %. However, in-hospital mortality after bailout was still high (28.37 % in 2020). The standardized rates of overall mortality and surgical bailout between 2018 and 2020 were significantly lower for balloon-expandable and self-expanding transfemoral TAVR than for transapical TAVR after risk adjustment [transapical/transfemoral balloon-expandable/transfemoral self-expanding TAVR: in-hospital mortality: 5.66 % (95 % CI 4.81 %; 6.52 %)/2.30 % (2.03 %; 2.57 %)/2.32 % (2.07 %; 2.57 %); surgical bailout: 2.33 % (1.68 %; 2.97 %)/0.79 % (0.60 %; 0.98 %)/0.42 % (0.31 %; 0.53 %)]. Coronary artery disease [risk-adjusted OR = 1.50 (1.21; 1.85), p < 0.001] and atrial fibrillation [OR = 1.29 (1.07; 1.57), p = 0.009] were found to be the main risk factors for bailout., Conclusions: Rates of TAVR with need for a surgical bailout and overall in-hospital mortality have declined noticeably over the years in Germany. However, the outcomes are still unfavorable after surgical bailout, as in-hospital mortality is continuously high. We present risk factors for surgical bailout to improve preparation of subsequent measures. It must be a major goal to further reduce the rate of surgical bailouts in the future., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background:  Literature demonstrated that procedure volumes affect outcomes of patients undergoing transcatheter aortic valve implantation. We evaluated the outcomes of surgical aortic valve replacement., Methods:  All isolated surgical aortic valve replacement procedures in Germany in 2017 were identified. Hospitals were divided into five groups from ≤25 (very low volume) until >100 (very high volume) annual procedures., Results:  In 2017, 5,533 patients underwent isolated surgical aortic valve replacement. All groups were of comparable risk (logistic EuroSCORE, 5.12-4.80%) and age (66.6-68.1 years). In-hospital mortality and complication rates were lowest in the very high-volume group. Multivariable logistic regression analyses showed no significant volume-outcome relationship for in-hospital mortality, stroke, postoperative delirium, and mechanical ventilation > 48 hours. Regarding acute kidney injury, patients in the very high-volume group were at lower risk than those in the very low volume group (odds ratio [OR] = 0.53, p  = 0.04). Risk factors for in-hospital mortality were previous cardiac surgery (OR = 5.75, p  < 0.001), high-grade renal disease (glomerular filtration rate < 15 mL/min, OR = 5.61, p  = 0.002), surgery in emergency cases (OR = 2.71, p  = 0.002), and higher grade heart failure (NYHA [New York Heart Association] III/IV; OR = 1.80, p  = 0.02). Risk factors for all four complication rates were atrial fibrillation and diabetes mellitus., Conclusion:  Patients treated in very low volume centers (≤25 operations/year) had a similar risk regarding in-hospital mortality and most complications compared with very high-volume centers (>100 operations/year). Only in the case of acute kidney injury, very high-volume centers showed better outcomes than very low volume centers. Therefore, surgical aortic valve replacement can be performed safely independent of case volume., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Previously, overall comparable outcomes were seen for balloon-expandable (BE) or self-expanding (SE) transfemoral transcatheter aortic valve replacement (TAVR). However, subgroup analyses based on large case numbers are still needed., Methods: German national data of all BE and SE transfemoral TAVR treating aortic valve stenosis in 2019 and 2020 were analysed. We then compared different outcomes and performed a subgroup analysis for the endpoint in-hospital mortality., Results: Overall, 46,243 TAVR were analysed, 19,910 BE, and 26,333 SE. Patients in the SE group had a significantly higher logistic EuroSCORE (13.61 vs 12.66%, p < 0.001), age (81.55 vs 79.99a, p < 0.001), and proportion of women (54.82 vs 40.06%, p < 0.001). Both groups showed a similar in-hospital mortality with 2.37% in BE and 2.35% in SE (p = 0.916). In-hospital mortality also did not differ significantly after risk adjustment (OR = 0.98 [0.86, 1.13], p = 0.799). Patients in the SE group had a significantly lower risk of major bleeding (OR = 0.83 [0.73, 0.95], p = 0.006), but a significantly higher risk of stroke (OR = 1.38 [1.19, 1.59], p < 0.001), delirium (OR = 1.15 [1.06, 1.24], p = 0.001), and permanent pacemaker implantation (OR = 1.29 [1.21, 1.37], p < 0.001). In the subgroup analysis of in-hospital mortality, there were no significant differences in any of the observed subgroups (age < 75/75-79/80-84/ ≥ 85a, logistic EuroSCORE < 4/4- < 9/ ≥ 9, gender, NYHA III/IV, previous CABG, peripheral vascular disease, COPD, pulmonary hypertension, renal disease GFR < 30 ml/min, and diabetes mellitus)., Conclusion: In the direct comparison of balloon-expandable and self-expanding TAVR, there are no differences for in-hospital mortality in subgroups., (© 2023. The Author(s).)

Aims: Literature on percutaneous coronary intervention (PCI) stated an inverse relationship between hospital volume and mortality, but the effects on other characteristics are unclear., Methods: Using German national records, all coronary angiographies with coronary artery disease in 2017 were identified. We applied risk-adjustment to account for differences in population characteristics., Results: Of overall 528,188 patients, 55.22% received at least one stent, with on average 1.01 stents implanted in all patients. Based on those patients who received at least one stent, this corresponds to an average number of 1.82 stents. In-hospital mortality across all patients was 2.93%, length of hospital stay was 6.46 days, and mean reimbursement was €5,531. There were comparatively more emergency admissions in low volume centers and more complex cases (3-vessel disease, left main stenosis, and in-stent stenosis) in high volume centers. In multivariable regression analysis, volume and likelihood of stent implantation ( p =0.003) as well as number of stents ( p =0.020) were positively correlated. No relationship was seen for in-hospital mortality ( p =0.105), length of stay ( p =0.201), and reimbursement ( p =0.108). Nonlinear influence of volume suggests a ceiling effect: In hospitals with ≤100 interventions, likelihood and number of implanted stents are lowest (∼34% and 0.6). After that, both rise steadily until a volume of 500 interventions. Finally, both remain stable in the categories of over 500 interventions (∼60% and 1.1)., Conclusion: In PCI, lower volume centers contribute to emergency care. Higher volume centers treat more complex cases and show a higher likelihood of stent implantations, with a stable safety., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Vera Oettinger et al.)

Aims: Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2., Methods and Results: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM-10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3-10 µM (by 20-32%/25-30%/44-45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3-3 µM., Conclusion: A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: In pure aortic regurgitation, transcatheter aortic valve replacement (TAVR) is not yet used on a regular base. Due to constant development of TAVR, it is necessary to analyze current data., Methods: By use of health records, we analyzed all isolated TAVR or surgical aortic valve replacements (SAVR) for pure aortic regurgitation between 2018 and 2020 in Germany., Results: 4,861 procedures-4,025 SAVR and 836 TAVR-for aortic regurgitation were identified. Patients treated with TAVR were older, showed a higher logistic EuroSCORE, and had more pre-existing diseases. While results indicate a slightly higher unadjusted in-hospital mortality for transapical TAVR (6.00%) vs. SAVR (5.71%), transfemoral TAVR showed better outcomes, with self-expanding compared to balloon-expandable transfemoral TAVR having significantly lower in-hospital mortality (2.41% vs. 5.17%; p  = 0.039). After risk adjustment, balloon-expandable as well as self-expanding transfemoral TAVR were associated with a significantly lower mortality vs. SAVR (balloon-expandable: risk adjusted OR = 0.50 [95% CI 0.27; 0.94], p  = 0.031; self-expanding: OR = 0.20 [0.10; 0.41], p  < 0.001). Furthermore, the observed in-hospital outcomes of stroke, major bleeding, delirium, and mechanical ventilation >48 h were significantly in favor of TAVR. In addition, TAVR showed a significantly shorter length of hospital stay compared to SAVR (transapical: risk adjusted Coefficient = -4.75d [-7.05d; -2.46d], p  < 0.001; balloon-expandable: Coefficient = -6.88d [-9.06d; -4.69d], p  < 0.001; self-expanding: Coefficient = -7.22 [-8.95; -5.49], p  < 0.001)., Conclusions: TAVR is a viable alternative to SAVR in the treatment of pure aortic regurgitation for selected patients, showing overall low in-hospital mortality and complication rates, especially with regard to self-expanding transfemoral TAVR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Oettinger, Hilgendorf, Wolf, Stachon, Heidenreich, Zehender, Westermann, Kaier and von zur Mühlen.)

Background: COVID-19 has caused the deferral of millions of elective procedures, likely resulting in a backlog of cases. We estimate the number of postponed surgical aortic valve replacement (sAVR) and transcatheter aortic valve replacement (TAVR) procedures during the first two waves of the COVID-19 pandemic in Germany., Methods: Using German national records, all isolated TAVR and sAVR procedures between 2007 and 2020 were identified. Using weekly TAVR and sAVR procedures between 2017 and 2019, we created a forecast for 2020 and compared it with the observed number of procedures in 2020., Results: In Germany, a total of 225,398 isolated sAVR and 159,638 isolated TAVR procedures were conducted between 2007 and 2020 that were included in our analysis. The reduction in all AVR procedures (sAVR and TAVR) for the entire year 2020 was 19.07% (95%CI: 15.19-22.95%). During the first wave of the pandemic (week 12-21), the mean weekly reduction was 32.06% (23.44-40.68%) and during the second wave of the pandemic (week 41-52), the mean weekly reduction was 25.58% (14.19-36.97%). The number of sAVR procedures decreased more than the number of TAVR procedures (24.63% vs. 16.42% for the entire year 2020)., Conclusion: The first year of the COVID-19 pandemic saw a substantial postponing of AVR procedures in Germany. Postponing was higher for sAVR than for TAVR procedures and less pronounced during the second wave of the COVID-19 pandemic., (© 2023. The Author(s).)

Background: The COVID-19 pandemic led to extensive restrictions in Germany in 2020, including the postponement of elective interventions. We examined the impact on ST-elevation myocardial infarction (STEMI) as an acute and non-postponable disease., Methods: Using German national records, all STEMI between 2017 and 2020 were identified. Using the number of STEMI cases between 2017 and 2019, we created a forecast for 2020 and compared it with the observed number of STEMI in 2020., Results: From 2017 to 2020, 248,062 patients were treated for STEMI in Germany. Mean age was 65.21 years and 28.36% were female. When comparing forecasted and observed STEMI in 2020, a correlation can be seen: noticeable fewer STEMI were treated in those weeks respectively months with an increasing COVID-19 hospitalization rate (monthly percentage decrease in STEMI: March - 14.85%, April - 13.39%, November - 11.92%, December - 22.95%). At the same time, the crude in-hospital mortality after STEMI increased significantly at the peaks of the first and second waves (relative risk/RR of monthly in-hospital mortality: April RR = 1.11 [95% CI 1.02; 1.21], November RR = 1.13 [1.04; 1.24], December RR = 1.16 [1.06; 1.27])., Conclusion: The COVID-19 pandemic led to a noticeable decrease in the number of STEMI interventions in Germany at the peaks of the first and second waves in 2020, corresponding to an increase in COVID-19 hospitalizations. At the same time, in-hospital mortality after STEMI increased significantly in these phases. Impact of the COVID-19 pandemic on STEMI numbers and in-hospital mortality in Germany. Relative difference between forecasted and observed STEMI numbers (above figure), the relative risk of in-hospital mortality (middle figure) as well as number of new hospital admissions for COVID-19 per million inhabitants according to Roser et al. 27 (bottom figure)., (© 2022. The Author(s).)

Extracorporeal hemoadsorption with the CytoSorb adsorber is increasingly being used during the past years. The use in combination with extracorporeal membrane oxygenation (ECMO) is feasible, but frequency of its use and outcomes have not been assessed in larger cohorts. We analyzed all patients treated with veno-venous (VV) ECMO either with or without CytoSorb in Germany from 2017 to 2019. Data were retrieved from a nationwide claim dataset collected by the Research Data Center of the Federal Bureau of Statistics. During this three-year episode, 7,699 patients were treated with VV ECMO. Among these, the number of CytoSorb-treated patients constantly increased from 156 (6.6%) in 2017 to 299 (11.8%) in 2019. In this large cohort hemoadsorption with the CytoSorb adsorber was associated with higher mortality and increased treatment costs. Due to limited information in the dataset about the severity of disease comparison of outcomes of patients treated with and without CytoSorb has to be interpreted with caution. Further studies have to examine if this finding is due to a negative effect of hemoadsorption with the CytoSorb device or is rather to be attributed to disease severity., (Copyright © ASAIO 2022.)

Background: Severe aortic valve stenosis inhibits renal perfusion, thereby potentially worsening renal function, in particular in elderly patients most often assigned to transcatheter aortic valve implantation (TAVI). Pre-TAVI diagnostics and the procedure itself may adversely impact renal function, however renal perfusion and function may also improve post-procedure. This study aimed to clarify the impact of TAVI planning and procedure on kidney function METHODS: In this retrospective study, kidney function of patients who underwent transfemoral TAVI at a tertiary university hospital between 2016 and 2019 was analyzed. The present study investigated kidney function at baseline, after computed tomography (CT) was performed for evaluation of TAVI, after TAVI, at discharge and at follow-up., Results: Among 366 patients, the prevalence of acute kidney injury (AKI) was 14.5% after TAVI. Independent predictors of AKI were arterial hypertension, baseline creatinine, AKI post CT and coronary intervention during pre-procedural diagnostics. At discharge and follow-up, 2.1% and 3.4%, respectively had sustained relevant impairment of kidney function (defined as creatinine/baseline creatinine > 1.5 or renal replacement therapy). Patients with known chronic kidney disease showed no higher rates of short- and long-term impairment, but higher rates of improvement of renal function after TAVI., Conclusions: In most cases TAVI does not worsen renal function. A sustained impairment after TAVI was found in only a few cases. This was independent of reduced baseline kidney function. Transfemoral TAVI can thus be planned and performed even in patients with higher stages of chronic kidney disease.

Background: The hospital mortality of patients suffering from pulmonary failure requiring venovenous extracorporeal membrane oxygenation (V-V ECMO) or extracorporeal carbon dioxide removal (ECCO 2 R) is high. It is unclear whether outcome correlates with a hospital's annual procedural volume., Methods: Data on all V-V ECMO and ECCO 2 R cases treated from 2007 to 2019 were retrieved from the German Institute for Medical Documentation and Information. Comorbidities and outcomes were assessed by DRG, OPS, and ICD codes. The study population was divided into 5 groups depending on annual hospital V-V ECMO and ECCO 2 R volumes (<10 cases; 10-19 cases; 20-29 cases; 30-49 cases; ≥50 cases). Primary outcome was hospital mortality., Results: A total of 25 096 V-V ECMO and 3607 ECCO 2 R cases were analyzed. V-V ECMO hospitals increased from 89 in 2007 to 214 in 2019. Hospitals handling <10 cases annually increased especially (64 in 2007 to 149 in 2019). V-V ECMO cases rose from 807 in 2007 to 2597 in 2019. Over 50% of cases were treated in hospitals handling ≥30 cases annually. Hospital mortality was independent of the annual hospital procedural volume (55.3%; 61.3%; 59.8%; 60.2%; 56.3%, respectively, p = 0.287). We detected no differences when comparing hospitals handling <30 cases to those with ≥30 annually (p = 0.659). The numbers of ECCO 2 R hospitals and cases has dropped since 2011 (287 in 2007 to 48 in 2019). No correlation between annual hospital procedural volume and hospital mortality was identified (p = 0.914)., Conclusion: The number of hospitals treating patients requiring V-V ECMO and V-V ECMO cases rose from 2007 to 2019, while ECCO 2 R hospitals and their case numbers decreased. We detected no correlation between annual hospital V-V ECMO or ECCO 2 R volume and hospital mortality., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The literature has shown an inverse volume-outcome relationship for transcatheter aortic valve implantation (TAVI). However, little is known about emergency admissions in Germany. Using German national electronic health records, we identified all isolated balloon-expandable and self-expanding transfemoral TAVI in 2018. The focus was on those patients with emergency admission. 17,295 patients were treated with TAVI, including 1682 emergency cases. 49.2% of the emergency admissions were female, the mean age was 81.2 years and the logistic EuroSCORE was 23.3%. The percentage of emergency cases was higher in lower volume than in higher volume centers (p < 0.001): In detail, centers performing < 50 TAVI showed an emergency admission rate of ~ 15%, those with > 200 TAVI a rate of ~ 11%. After propensity score adjustment, analyzing the outcomes for an increase in volume per 10 emergency admissions, higher volume centers showed significantly better outcomes regarding in-hospital mortality (OR = 0.872, p = 0.043), major bleeding (OR = 0.772, p = 0.001), stroke (OR = 0.816, p = 0.044), mechanical ventilation > 48 h (OR = 0.749, p = 0.001), length of hospital stay (risk adjusted difference in days of hospitalization per 10 emergency admissions: - 1.01 days, p < 0.001), and reimbursement (risk adjusted difference in reimbursement per 10 emergency admissions: -€314.89, p < 0.001). Results were not significant for acute kidney injury (OR = 0.951, p = 0.104), postoperative delirium (OR = 0.975, p = 0.480), and permanent pacemaker implantation (OR = 1.010, p = 0.732). In conclusion, regarding transfemoral TAVI, the percentage of emergency cases was higher in lower volume centers in Germany. However, higher volume centers show significantly better outcomes for in-hospital mortality and complication rates as well as resource utilization parameters., (© 2022. The Author(s).)