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Background Evidence in non-ischaemic cardiogenic shock (CS), especially regarding prognostic markers and use of mechanical circulatory support (MCS), is scarce. Aim The aim of this study was to evaluate left ventricular ejection fraction (LVEF) as a prognostic marker as well as a factor to guide the use of MCS in non-ischaemic CS. Methods In this international observational study, patients with non-ischaemic CS (e.g. caused by severe de-novo or acute on chronic heart failure; but not by acute myocardial infarction) treated with or without MCS from 18 tertiary-care centers in five countries were enrolled. Cox regression models adjusted for age, sex, SCAI class, lactate, prior resuscitation, mechanical ventilation and pH were fitted to evaluate the association between LVEF and 30-day mortality as well as the interaction between MCS use, LVEF and 30-day mortality. Results A total of 807 patients were enrolled, of whom 387 (47,9%) were treated with and 418 (52.1%) without MCS; mean age was 63 [interquartile range (IQR) 51.5–72) years, 601 (74.5%) were male, 486 (60.2%) had acute on chronic heart failure, 221 (32.7%) had an ischaemic cardiomyopathy and 277 (34.5%) had prior cardiac arrest. The baseline LVEF was 20 (IQR 15–30) % and baseline lactate was 4.9 (IQR 2.6–8.5) mmol/l. There was no significant association between LVEF and 30-day mortality risk [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.74–1.22 if LVEF was considered as a continuous variable; HR 1.09, 95% CI 0.83–1.44 if LVEF was considered as a categorical variable with ≤20% vs. >20%]. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with a depressed LVEF (HR 0.74, 95% CI 0.52–1.05, interaction-p = 0.04). Conclusion In this retrospective, multicenter, international study of patients with non-ischaemic CS, LVEF was not a predictor of 30-day mortality risk. However, we observed a significant interaction between MCS use and LVEF, indicating a lower morality risk with MCS use only in patients with a depressed LVEF. This provides rationale to use LVEF as a parameter to guide MCS therapy in non-ischaemic CS, and calls for a randomized trial on this topic. Funding Acknowledgement Type of funding sources: None.

Background and aims Low-density lipoprotein cholesterol (LDL-C) reduction is an essential part of the 2019 ESC/EAS dyslipidemia guidelines [1]. Only 18% of patients achieve 2019 ESC/EAS LDL-C target goal in secondary prevention [2]. “Jena auf Ziel – JaZ” (“Jena on target”) is a prospective study that aims at LDL-C target attainment in all patients with ST-elevation myocardial infarction (STEMI) and determination of reasons for failed target attainment. Methods All STEMI patients were started on atorvastatin 80 mg/ezetimibe 10 mg on admission. LDL-C levels were monitored during the hospital stay and a 12 months follow-up period. Patients were educated about cardiovascular risk factor optimization. Individual patient cards to document LDL-C levels over time were used to enforce LDL-C target attainment. Results In the first 50 consecutive patients, LDL-C levels were 3.39±1.23 mmol/L on admission, 1.84±0.86 mmol/L on discharge and 1.30±0.65 mmol/L during the first follow-up visit (6–8 weeks). On atorvastatin 80 mg/ezetimibe 10 mg 14 out of 50 patients (28%) reached the LDL-C goal on discharge, 36 out of 50 patients (72%) after 6–8 weeks. After addition of bempedoic acid or PCSK9-inhibitors all patients which were followed up in our lipid clinic reach the EAS/ESC-LDL-C target. Only two patients reported myalgias of which one patient refused to continue with lipid-lowering drugs. One patient had elevated liver enzymes, which resolved after switching to a lower statin dose. Conclusions One out three STEMI patients reached the EAS/ESC-LDL-C target during the initial hospital stay on atorvastatin 80 mg/ezetimibe 10 mg. Adding bempedoic acid or PCSK9 inhibitors resulted in LDL-C target attainment of all patients during follow-up. EAS/ESC-LDL-C target attainment is feasible and well-tolerated in empowered, well-educated patients. Funding Acknowledgement Type of funding sources: None.

Background Due to the high volume and broad availability of troponin testing and invasive coronary diagnostic in Germany, the entity of myocardial infarction with non-obstructive coronary arteries (MINOCA) is gaining increasing clinical and economic significance. As a main feature, no detectable obstructive coronary artery can be found upon angiography despite clinical symptoms related to acute coronary syndrome. Our investigation focuses on the procedural and economic impact of MINOCA and related clinical outcomes in a single-center patient collective of a university heart center. Methods All patients who were admitted to our hospital under the suspicion of an acute coronary syndrome within a 12-month period (2017–2018) for further diagnostics and treatment were screened. Included patients showed a pathological troponin elevation and received invasive coronary angiography. Associated costs, procedural and various clinical parameters as well as timelines and parameters of work-flow were obtained. Results 3021 patients were initially screened and 660 were included. Of those, 103 patients were attributed to the MINOCA group. 542 patients presented with a “classical” myocardial infarction, and thus formed the MIOCA (myocardial infarction with obstructive coronary arteries) group. Baseline characteristics were summarized in Table 1. MINOCA patients were less frail, less diabetic, more likely female and showed no relevant difference in age or other selected comorbidities. The emergency department was the primary point of hospital admission for >70% of the patients from both groups. 50% of the patients arrived in the afternoon on a weekday. MINOCA patients were less present during the weekend as MIOCA patients (8.5% vs. 19.7%; p=0.002). With regard to a potential seasonal occurrence, both MINOCA and MIOCA cases show a pattern with two peaks (Figure 1). In-hospital mortality (MIOCA vs. MINOCA: 59 (11.1%) vs. 0 (0%) patients; p Conclusion Despite MINOCA being mostly a benign syndrome with favorable clinical outcome, it still utilizes relevant financial and capacity resources including high care monitoring and an in-hospital treatment of relevant length. Funding Acknowledgement Type of funding sources: None.

Background Intravascular lithotripsy (IVL) is a relatively novel treatment option for calcified lesions in peripheral artery disease. Little is known about the mid to long-term functional status of the patients and target lesion revascularization rate (TLR) after IVL only procedure. Purpose To evaluate the course of ankle-brachial-index (ABI) and to assess the rate of revascularization 1 year after intravascular lithotripsy performed on calcified peripheral lesions. Methods Between December 2018 and January 2021 IVL was performed on 61 limbs of 51 patients presenting with Rutherford classes 2–5. Ankle-brachial-index (ABI) was documented before the procedure as well as 1 day, 6 months and 1 year after the procedure within a single center real-life registry. Further endpoint was revascularization with PTA or peripheral bypass surgery. The vast majority of cases were done as IVL only procedure (58%) All procedures were done in upper leg/pelvic stenosis. Results ABI measurement after 12 months was done in 42 of 51 patients (82%). Three pts were missed due to media sclerosis. Due to loss of follow-up, ABI after 6 months could not be performed on 4/61 patients (7,8%) and 12-month-ABI in another 8/51 cases (15,6%). Initial baseline ABI of 0.6±0.26 before the procedure increased to 0.8±0.25 (p Conclusions In our large single center registry, IVL performed mainly as a stand-alone procedure was safe and effective even after a mid-term follow up. TLR was necessary in 13%, which is lower than in previous published IVL data (20,7% as in DISRUPT-PAD-II) [1]. ABI after 12 months improved but did maintain statistical significance, compared with other procedure like scoring balloon [2]. Funding Acknowledgement Type of funding sources: None.

Background Elevated levels of uric acid (UA) have been associated with worsening of outcomes in cardiovascular and renal disease and may lead to gout. Patients with acute decompensated heart failure (ADHF) may develop hyperuricemia under intensified diuretic treatment. In this setting, the effect of empagliflozin on serum uric acid remains unknown. Aim/Purpose The aim of this subanalysis in patients with ADHF was to assess how additive treatment with empagliflozin influences the concentration of serum uric acid and potential related outcomes. Methods In the single-center, prospective, double-blind, placebo-controlled EMPAG-HF trial, patients with ADHF were screened and randomized within 12 hours following hospital admission to receive either empagliflozin 25 mg or placebo in addition to standard medical treatment over five days. Sixtypatients (mean age 74,7±9,9, 39% female) were enrolled and randomized 1:1 irrespective of left ventricular ejection fraction or the presence of diabetes. UA in serum was determined daily and renal handling of UA was evaluated by fractional excretion of UA (FEUA). Two-way mixed ANOVA and Wilcoxon rank-sum test were used for statistical analyses. Results The empagliflozin group comprised 30 patients and the placebo group comprised 29 patients. There were no differences in baseline patient characteristics including LVEF, NT-proBNP, eGFR, HbA1c. In the placebo group, UA increased from baseline 487.86±32.21 μmol/l to 500.38±28.37 μmol/l at day (d) 2 (p=0.045), 512.36±29.43 μmol/l at d3 (p=0.018), and 518.46±31.14 μmol/l at d4 (p=0.021). By contrast, in the empagliflozin group, UA tended to decrease compared to baseline and was significantly lower compared to placebo at d3 (436.08±23.94 vs. 512.36±29.43 μmol/l, p=0.049), d4 (423.20±24.12 vs. 518.46±31.14 μmol/l, p=0.018), and d5 (423.17±24.75 vs. 508.62±31.08 μmol/l, p=0.037). Serum UA returned to baseline levels in both groups 30 days after cessation of empagliflozin. The reduction of UA in the empagliflozin group was associated with a significant enhancement in FEUA (5.49±0.81% vs. 9.38±1.07%, p=0.004). Conclusion Our data suggest that the additive treatment with empagliflozin in patients with acute decompensated heart failure lowers the levels of serum uric acid compared to loop diuretics alone. This effect may be attributed to an improved renal elimination of UA and a better preservation of kidney function. It remains to be clarified whether this uricosuric effect of empagliflozin also contributes to its prognostic benefits in heart failure. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University, Jena, Germany) Boehringer Ingelheim Inc.

Background The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is recommended in the current resuscitation guidelines of the European Resuscitation Council as a rescue attempt for selected patients for whom extended resuscitation measures do not lead to the establishment of a spontaneous circulation (ROSC). We aim to characterize and investigate the value of neuron specific enolase (NSE) for assessing the neurological prognosis after cardiopulmonary resuscitation (CPR) as these have so far only been evaluated in resuscitated patients without extracorporeal circulatory support. Methods We retrospectively analyzed the records of patients, who received a VA-ECMO under ongoing CPR between 2004 and 2021 and were treated in a cardiac intensive care unit (ICU) of a university, tertiary care center. Outcome will be measured clinically by using the Glasgow Outcome Score (GOS) four weeks after ICU discharge. Neurological prognosis will be estimated by serum concentration of NSE (baseline until 96h). Serum free hemoglobin (fHb, baseline until 96h) serves as a marker for identifying a potential confounding effect of relevant parallel hemolysis. Results 190 patients were included in our study (baseline characteristics, Figure 1). 154 patients (84.5%) died within 4 weeks after ICU admission or remained unconscious (GOS 1+2), 29 survived (15.5%) with a residual slight to severe neurological deficit (GOS 3–5). Mean duration of VA-ECMO treatment was 103.4±112.1 h. In a wake-up attempt 48–96 h after CPR, patients with GOS 3–5 showed significantly more frequent adequate responses to speech (84% vs. 30.3%; p Conclusion The neuroprotein NSE makes an early, neurological, prognostic assessment of resuscitated patients possible even during VA-ECMO treatment and could be used in sedated patients as a biomarker for evaluation of treatment decision in acute heart failure such as therapy continuation, eligibility for heart transplantation or LVAD implantation. Funding Acknowledgement Type of funding sources: None.

Aim To evaluate the impact of timing of active left ventricular (LV) unloading in relation to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) implantation on outcomes of patients with cardiogenic shock (CS). Methods and results Data from 421 patients with CS treated with active LV unloading on top of VA-ECMO at 18 tertiary-care centers in 4 countries were collected. Only patients in whom both devices were implanted within 24 hours of each other were considered and patients were stratified by timing of device implantation in early vs. delayed active LV unloading (e.g. active LV unloading before vs. after VA-ECMO). Cox and logistic regression models (adjusted for age, sex, lactate, cardiopulmonary resuscitation (CPR), VA-ECMO assisted CPR and enrollment center) were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as several safety outcomes. Overall, 310 (73.6%) patients were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (hazard ratio 0.63, 95% confidence interval 0.46–0.87) and a higher likelihood of weaning from mechanical ventilation (odds ratio 1.25, 95% confidence interval 1.03–1.52), but not with more complications. Importantly, postponing active LV unloading in these patients was associated with higher mortality risk (Figure 1), and lower likelihood of successful weaning from mechanical ventilation. Conclusion This exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO as a primary treatment strategy, as opposed to a bail-out approach. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted research grant from Abiomed

Background Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy that leads to severe heart failure and, once clinically relevant, poses a high mortality risk. Epidemiological data for CA are still sparse and heterogeneous, but urgently needed since novel therapies against ATTR-CA are now available. Aim We aimed to assess minimum prevalence rates of CA among cardiac and non-cardiac patients undergoing routine echocardiography in an echo lab of a large university clinic serving all medical specialities in central Germany. Methods We established a retro- and prospective database based on suspicious findings in echocardiography for all echocardiographic exams over an 8.5 year period (03/2013 and 09/2021). During this time, 41,375 patients underwent at least one echo exam. Indication for echos were mixed, and consisted of non-cardiac and cardiac patients with acute and chronic illnesses as well as screening exams (e.g. before major surgery or chemotherapy). Suspicious echocardiography were retrospectively analysed whether they underwent further diagnostic or if it remained an unproven suspicion (figure). All echos of suspicious cases were comprehensively re-analysed regarding novel surrogate parameters and indices for CA. Various clinical and laboratory parameters were collected. Results The mean age of the cohort of 41,375 patients was 65.1±15.8 years for the first or only echo examination with a slightly unbalanced gender distribution (45% female). The age distribution is shown in the table. While 128 patients were suspected, the diagnosis was falsified in 16 patients and proven in 47 patients (light chain n=16, ATTR n=31; figure). A substantial proportion of patients with suspicious echo received no further diagnostic work-up (N=65). Over the given time frame of 101 months, the prevalence of suspicious echocardiograms was 1 per 323 patients (or 31 per 10,000). The proven cases had a prevalence of 1 per 880 patients (or 11.3 per 10,000). Since ATTR-CA is a disease of the elderly, we saw a vanishingly small number of cases in persons younger than 70 years (table), whereas 90% of all CA patients were older than 70 years. At timing of diagnosis, AL-CA patients were almost 10 years younger compared to diagnosis of ATTR-CA (69.1±8.4 years vs. 77.4±8.5 years). In patients older than 80 years, the prevalence rate of ATTR-CA peaked with 22.6 cases per 10.000 patients (0.23%). The prevalence rate of ATTR-CA was roughly twice as high compared to AL-CA. Conclusion For the first time, an estimation of minimum prevalence rates for CA for a defined volume of echocardiograms in an all-comers population is provided. In a mixed population of a hospital of maximum care CA prevalence rate is much higher than expected. Awareness for this “rare” disease is needed, since routine echo exams can prompt suspicion in clinically silent or so far unrecognized CA cases. Funding Acknowledgement Type of funding sources: None.

Background Transcatheter aortic valve implantation (TAVI) is the accepted state-of-the-art treatment for elderly patients suffering from severe symptomatic aortic stenosis (AS). Co-morbidities at baseline are of great impact not only for individual peri-procedural risk stratification but also for the determination of long-term prognosis. The latter is of certain clinical interest, since a variety of co-existing disorders can be effectively treated in addition to TAVI. Purpose The current study aimed to elucidate the prognostic value of a wide range of baseline characteristics and co-morbidities with respect to long-term survival of TAVI patients in a prospective real-world single-center registry study. Methods A total of 445 patients with severe AS, which were treated by transfemoral TAVI, were included. A wide range of clinical, laboratory, functional and imaging parameters were prospectively assessed at baseline prior to TAVI. Mortality was recorded at 30 days, 1 year and 2 years after TAVI. Results The mean age of patients in this typical TAVI cohort was 78.7±7.3 years, 52% were female and the mean STS score was 5±3.9%. The mortality rates were as follows: 3.6% after 30 days, 16.4% after 1 and 22.6% after 2 years. Multivariate analysis could identify the following independent predictors of 2-year mortality assessed at baseline: sex, age, AS entity other than high-gradient, atrial fibrillation (Afib), renal function, relevant TR, systolic pulmonary artery pressure (PAPsys) and six-minute walk distance (SMWD). Among those, the strongest predictive value could be shown for Afib (OR 2.505, CI 1.509–4.157, p Conclusions Taken together, the results of the current study demonstrate the prognostic value of cardiovascular co-morbidities assessed prior to TAVI. We identified relevant TR and Afib as the strongest independent predictors of long-term mortality in our cohort. Since both conditions are effectively treatable, special emphasis should be placed on the question, which patient might benefit from treatment, e.g., by transcatheter edge-to-edge repair of TR or rhythm control, in addition to TAVI. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Else Kröner-Fresenius-Stiftung, Research Program “Else Kröner-Forschungskolleg AntiAge”

Background Transcatheter aortic valve implantation (TAVI) has developed rapidly in the last decade and is now recommended as state-of-the-art treatment for elderly patients suffering from severe symptomatic degenerative aortic stenosis (AS). The extent of mitral regurgitation (MR) following TAVI is likely to be of prognostic relevance. This raises the question whether treating MR following TAVI improves outcome of patients with significant MR. Purpose The current study was aimed to elucidate the prognostic value of MR at different follow-up (FU) timepoints after TAVI in a prospective real-world single-center registry study. Methods A total of 445 patients with severe AS, which were treated by transfemoral TAVI, were included and a wide range of clinical, laboratory, functional and imaging parameters were prospectively assessed. Mortality was recorded at 30 days, 1 year and 2 years after TAVI. Complete FU data including echocardiography were available at 6 to 8 weeks (n=334) as well as 6 months (n=235) after TAVI. Results All patients (mean age: 78.7±7.3 years, 52% female, mean STS score: 5±3.9%) were successfully treated by transfemoral TAVI using balloon- or self-expanding prostheses and showed mortality rates of 3.6% after 30 days, 16.4% after 1 year and 22.6% after 2 years. Moderate or severe (relevant) MR was detectable in 39% of the patients at baseline, in 27% of patients after 6 weeks (p=0.001) and in 28% of patients after 6 months (p=0.036, compared to baseline). Multivariate analysis identified independent predictors of 2-year mortality: clinical frailty scale and PAPsys at 6 to 8 weeks post-TAVI as well as BNP and relevant MR 6 months post TAVI. Among those parameters, MR after 6 months was the strongest predictor of long-term mortality (OR 3.192, CI 0.971–10.487, p=0.056). Kaplan-Meier survival analysis displayed significantly worse 2-year survival rates in patients suffering from relevant MR at 6 months (12.1% versus 4.8%, p=0.042). Conclusions Taken together, this real-life single-center experience underlines the prognostic value of relevant MR 6 months after TAVI with respect to long-term survival. Interestingly, MR was not predictive at the 6 to 8 weeks FU suggesting that early remodeling includes MR with prognostic relevance in those patients. Whether MR treatment, e.g., by transcatheter edge-to-edge repair, will improve patient outcomes post-TAVI has to be tested in prospective trials. Funding Acknowledgement Type of funding sources: None.

Background and aims Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9) (1). Previous studies suggest that inclisiran provides sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. Patients included in the ORION program received inclisiran on top of maximally tolerated statin therapy and demonstrated a profound 50% LDL-C reduction as early as 3 months (2). The aim of this retrospective, multi-center analysis was to use individual patient data to determine the extent of the variability in LDL-C reduction in response to inclisiran administration in a real-world setting. Methods Since February 2021 the German Inclisiran Network (GIN) enrolled patients who received inclisiran due elevated LDL-cholesterol (LDL-C) levels in German lipid clinics. In contrast to patients included in the ORION program inclisiran could be administered to a broad range of patients with elevated LDL-C levels, including patients naive of lipid-lowering drugs, as well as patients on apheresis who failed to attain LDL-C goals. Results In 10 lipid clinics in Germany a total of 117 consecutive patients received inclisiran. Patients, who were not on stable lipid-lowering medication at least 3 months prior to inclisiran administration, were excluded. Thus, a total of 61 patients were analyzed. Mean LDL-C level at baseline was 151.86±64.31 mg/dl (95 percent confidence interval (CI): 135.39 to 168.33 mg/dl). After 3 months, inclisiran reduced LDL-C levels by 34.6% (95% CI: 29.3 to 39.8%), mean LDL-C levels were 103.26±60.36 mg/dl (95% CI: 87.8 to 118.72 mg/dl). At baseline 18 (30%) patients received statins, 22 (36%) ezetimibe and 13 (21%) bempedoic acid. Twenty-five (41%) patients were not on any lipid lowering therapy at baseline and 15 (25%) were on apheresis and failed to attain LDL-C target levels at baseline. Altogether there was a high inter-individual variability in LDL-C reduction 3 months after the first administration of inclisiran (Figure 1). Interestingly, patients who received statins at baseline demonstrated a trend towards a more profound LDL-C reduction (42.6±20.6 vs. 30.33±19.2%). This effect, however, was not significant. Two patients did not demonstrate any LDL-C reduction after the first administration. Inclisiran was well tolerated. Only one patient reported a minor injection-site reaction. No further side-effects were reported. Conclusion These results indicate that there is substantial individual variability in the LDL-C reduction after the first administration of inclisiran. Inclisiran was well tolerated without any serious side-effects. A longer follow-up period and further research is warranted to elucidate reasons for the high inter-individual variability in LDL-reductions in this real-world setting. Funding Acknowledgement Type of funding sources: None.

Seit der letzten Herausgabe von Leitlinien zur Behandlung von Erwachsenen mit angeborenem Herzfehler durch die European Society of Cardiology (ESC) im Jahr 2010 sind umfangreiche neue Daten publiziert worden, die eine Neuauflage des Dokuments erforderlich gemacht haben. Dies betrifft insbesondere die katheterinterventionelle Behandlung von Herzfehlern, die Risikostratifizierung mit Hinblick auf den optimalen Zeitpunkt fur Intervention und Re-Intervention, aber auch die medikamentose Therapie und die Versorgungsstrukturen. Der vorliegende Kommentar fasst die wesentlichen Neuerungen zusammen und nimmt Bezug auf Besonderheiten in Deutschland.

Die im August 2019 publizierte ESC-Leitlinie zu Diagnose und Management des chronischen Koronarsyndroms ersetzt die zuletzt 2013 veroffentlichten Handlungsempfehlungen bei Patienten mit stabiler chronischer koronarer Herzerkrankung. Diese aktualisierte Leitlinie fuhrt als auffalligste Veranderung mit der Bezeichnung „chronisches Koronarsyndrom“ eine neue Terminologie ein, die den dynamischen Charakter der koronaren atherosklerotischen Erkrankung unterstreichen soll. Ebenfalls neu eingebracht wurden 6 klinische Szenarien, anhand derer die weitere Diagnostik und Therapieempfehlungen in den Leitlinien erortert werden. Die hierbei notwendige Bestimmung von Pratestwahrscheinlichkeiten wurde um den Begriff der „klinischen Wahrscheinlichkeit“ erganzt. Eine wesentliche Abwertung bei der nichtinvasiven Diagnostik einer koronaren Herzerkrankung erfahrt das Belastungs-EKG, welches nur noch als Alternativtest empfohlen wird, falls andere nichtinvasive oder invasive Bildgebungsverfahren nicht zur Verfugung stehen. In diesem Zusammenhang wird die Bedeutung der koronaren Computertomographie gestarkt. Ist eine Koronarangiographie zur Diagnose einer KHK notwendig, so soll – abgesehen von wenigen Ausnahmen – bei Fehlen eines klaren regionalen Ischamienachweises eine funktionelle invasive Messmethode regelhaft vor einer PCI eingesetzt werden. Erstmalig finden sich ausfuhrliche Empfehlungen zur antithrombotischen Medikation. Im Gegensatz zu den vorherigen Leitlinien wird die Notwendigkeit der weiterfuhrenden Diagnostik und Behandlung von symptomatischen Patienten ohne Nachweis von Stenosen der epikardialen Koronararterien betont, ebenso wie das Management von Patienten mit refraktarer Angina pectoris.

Die Mitral- und Trikuspidalklappeninsuffizienz sind haufige Herzklappenerkrankungen. Sie gehen als unabhangige Risikofaktoren mit einer erhohten Sterblichkeit bei Herzinsuffizienz einher. Die kathetergestutzte Rekonstruktion der Klappen stellt eine mittlerweile relevante Alternative zur rein medikamentosen bzw. chirurgischen Behandlung dar. Wahrend die kathetergestutzte Therapie der Trikuspidalklappeninsuffizienz in ersten Registern Effektivitat und Sicherheit demonstrierte, liegen fur die kathetergestutzte Therapie der Mitralklappeninsuffizienz mittlerweile mehrere randomisierte Studien vor. Dieses Papier stellt die Ergebnisse aktueller Studien dar und gibt Empfehlungen zur Indikation interventioneller Behandlungsverfahren bei Mitral- und Trikuspidalklappeninsuffizienz. Zur Sicherung der Qualitat dieser Verfahren werden von der Deutschen Gesellschaft fur Kardiologie die Kriterien fur die Zertifizierung von Zentren zur kathetergestutzten Therapie der Mitralklappeninsuffizienz aktualisiert.

Background Transcatheter tricuspid valve repair (TTVr) is a novel modality for treatment of severe tricuspid regurgitation (TR) in patients at high surgical risk. So far, the most frequently used system is the MitraClip® providing two different clip types (NTR vs XTR). Purpose To compare XTR vs NTR clip systems for TTVr regarding safety, feasibility, and effectiveness. Methods 35 consecutive high-risk patients (78.4±7.9 years, EUROScore II 10.7±10.8%, STS Score 7.9±4.1) with symptomatic TR were treated using the MitraClip® system between 2017–2020. with an NTR (N=18, 51.4%) or XTR (N=17, 48.6%) system. The primary outcome was successful TTVr with TR reduction of ≥1 grade with no mortality, single leaflet device attachment (SLDA), or conversion to surgery until hospital discharge. At 30-day follow-up, TR severity grade and NYHA functional class were assessed. Results We found more severe initial TR grades in the XTR group compared to the NTR group expressed with wider TR V. contracta (14.8±4.3 vs 11.1±3.8 mm, p=0.011), larger EROA (0.99±0.4 vs 0.72±0.3 cm2, p=0.032), wider coaptation depth (9.6±2.8 vs 7.3±0.4 mm, p=0.036) and V. cava inferior (30.7±3.6 vs. 25.8±6.4 mm in NTR, p=0.013). 5 patients (29.4%) in the XTR and 3 patients (16.7%) in the NTR group presented initially with torrential TR. No significant differences were observed for clinical characteristics, comorbidities, co-medication, laboratory parameters or initial NYHA functional class (3.0±0.5 in NTR vs 3.2±0.4 in XTR, p=0.45). TTVr was safe with no intraprocedural deaths, emergency surgery or major vascular complications. Duration of the procedure and fluoroscopy did not differ. Both, NTR and XTR system led to procedural success in 72.2% (N=13) and 76.5% (N=13), respectively. At discharge, a significant reduction of initial TR grade was observed in both groups (2.4±0.9 in NTR and 2.3±0.9 in XTR, p Conclusion MitraClip® NTR and XTR systems for TTVr of severe TR in high-risk patients are safe and effective leading to a significant reduction of TR and clinical improvement. The XTR system seems to allow successful treatment of more severe TR stages compared to NTR. Funding Acknowledgement Type of funding sources: None.

Background Liver transplantation (LTx) is often the only treatment strategy in patients with advanced liver disease. Since the donor pool is limited, careful preoperative examination of the cardiac functional status is crucial. Especially the presence of pulmonary hypertension (PH) either coincidental or as part of porto-pulmonary hypertension (PoPHT) is known to play a prognostic role in post-transplant survival and graft durability. However, right heart function itself may play a role even in the absence of PH. Purpose We retrospectively evaluated right heart function data acquired during transthoracic echocardiography (TTE) in the evaluation process for LTx listing to identify patient populations at risk for poor long-term prognosis. Methods We performed a single-center retrospective cohort study of patients that underwent LTx between 2011 and 2020. All patients ultimately underwent LTx; Survival data were assessed at 90 days, 1 year and 3 years. The waiting period from time of cardiac assessment to the actual operation was blinded. We evaluated right heart end-diastolic diameter (RVEDd), tricuspid annular plane systolic excursion (TAPSE), as well as right atrial area (RAA). We pre-specified cut-offs for abnormal values with RVEDd above 39 mm, TAPSE below 18 mm and RAA above 16 cm2. Results We evaluated 351 patients who underwent LTx. 247 data sets were complete and could be included in the primary analysis (mean age 56.3±10.3 years, 75.7% male). Patients had a median Lab-MELD-Score of 14 points (IQR: 10–21 points). 23.8% of patients received a living donor transplant. The left ventricular ejection fraction was not compromised in any of the subjects (mean LVEF: 68.6±9.0%). The median waiting time in days between TTE and LTx was 142 days (IQR: 37–434 days) The primary end-point of mortality occurred in 44 or 17.8% of patients over a Period of three years. In univariate Cox-regression the pre specified cut-offs for TAPSE and RAA were not associated with a statistically significant survival (HR 0.663, CI: 0.33–1.33, p: 0.25). However, univariate analysis revealed that increased RVEDd was associated with post-LTx survival (HR 1.98, CI: 1.09–3.58, p=0.025) as well as Log-Rank (Mantel-Cox) in the Kaplan-Meier-estimate (Chi2: 5.25, p:0.022). In multivariable analysis including several laboratory values as well as the Lab-Meld-Score (Figure 2), RVEDd group remained the only significant parameter predicting mortality (HR 2.12, CI: 1.02–4.41, p=0.04). The Kaplan Meier analysis showed a significant difference in survival at 3 years of follow-up. Combining right ventricle parameters in a secondary analysis did not provide any additional benefit in predicting survival Conclusion Analysis of right heart function and especially dilatation was able to provide additional information concerning long-term outcome post-LTx in this retrospective analysis even when taking into consideration that moderate to severe PH or PoPHT was ruled out beforehand. Funding Acknowledgement Type of funding sources: None.

Objective Peripheral vascular disease (PVD) is a major cause of morbidity and mortality with increasing need for interventional therapies. Vascular calcification increases risk of complications and may impair the effect of antiproliferative therapy. Intravascular lithotripsy (IVL) using pulsatile sonic pressure waves to modify intimal and medial calcium is a promising approach for those patients to overcome the drawbacks of vascular calcification. Purpose A single-center, prospective registry of patients undergoing peripheral lithotripsy was established. Periprocedural safety events as well as short and long term follow-up clinical data were evaluated. Methods A prospective review of cases using IVL was performed for the period from December 2018 to January 2021 at our center. Angiographic images were quantified by using the QVA 8.0 module, Medis Suite Version 3.2.60.4 developed by Medis Imaging Systems. Results 61 cases of IVL were performed in 51 patients with Rutherford class 3. Mean age was 71 years with 78% (28) of the patients being men. Diabetes was present in 80% and renal insufficiency in 47% of the cases. The median calcified lesion length treated was 82 mm (10; 390 mm) with a PACCS sore of 3 (1; 3), indicating a highly calcified status. In 41% (n=25), predilation was necessary. We treated 8 iliac-, 19 common femoral-, 52 superficial femoral-, 5 deep femoral-, 29 popliteal- and 2 crural- lesions with balloon sizes ranging from 4.0 to 7.0 mm. In 35 (57%) cases IVL was used as a stand-alone therapy, in the remaining 26 an adjunctive therapy (DCB and/or stent) was used. We were able to reach an acute luminal gain of 2.5 mm. A ballon rupture occurred in 6 (10%) cases. There were no other complications. Mean ABI improved from 0.6 to 0.8 (p Conclusion This first real-world data of IVL reports compelling safety of IVL in a complex, difficult-to-treat patient cohort. For the first time, clinical follow-up data were presented and demonstrated a sustained improved ABI after 6 months. This innovative approach will gain more interest in the future, especially since long term effects of paclitaxel eluting devices are controversially discussed. Funding Acknowledgement Type of funding sources: None. ABI initial follow-up

Background Arrhythmias in elderly patients (>70 years) are common in daily clinical practice. Most frequently, they are based on atrial fibrillation or other atrial tachycardia with an indication for oral anticoagulation and specific antiarrhythmic medications. The electrographic (ECG) documentation related to symptoms is essential before therapy initiation. In case of suspected AVNRT based on surface ECG, an electrophysiological study (EP) with ablation as curative strategy should be planned. Methods We analysed all patients >70 years with AVNRT diagnosed by electrophysiologic (EP) studies between May 2018 and December 2020. Results An EP study for suspected AVNRT was performed in 27 patients >70 years. The diagnosis of AVNRT was confirmed in 20 patients (75%). From all EP- studies with the diagnosis of AVNRT (n=93) in this period, 20 patients (22%) were older than 70 years (mean age 77 years with a range of 70–85 years), 12 were women. In most of the patients, the duration of symptoms was short (3 month). Only 4 patients had symptoms of paroxysmal tachycardia longer than 10 years. Except for 2 patients, all patients had at least one ECG- documentation (12- lead- ECG, Holter- ECG, telemetric ECG and/or in the loop recorder). In 12 patients, a 12- lead- ECG- documentation was available, in 5 patients the tachycardia has been registered in the Holter-ECG and in 1 in a loop recorder. In the 12- lead- ECG before ablation in sinus rhythm the PQ interval was with 196 (120- 300) ms in the upper range. In 16/ 20 patients was during the EP- study a sustained AVNRT (CL 410, 314- 538 ms) inducible. In the others, up to 3 typical AV- nodal- echo beats were induced in the EP- study. A slow pathway ablation/ modification was performed in all patients in typical position. In 2 patients, the implantation of a dual- chamber- pacemaker was necessary due to intermittent high- degree AV-nodal-block during the same hospital stay. In both patients, a first degree AV-block with PQ- interval of 250 and 300 ms was pre-existing. Discussion Especially for the elderly patients with new onset of clinical symptoms of arrhythmia, clinical anamnesis including an ECG- documentation is required for planning the therapeutic strategy. A borderline long PQ- interval as sign of an age- dependent fibrosis in the AV- node and, therefore, altered conduction properties in the AV node can be a cause of AVNRT in these older patients. In patients with pre-existing long PQ- interval (>250 ms), the risk of pacemaker implantation after successful ablation is higher. In this group of patients, medical therapeutic options are limited and often associated with the need of pacemaker implantation. Funding Acknowledgement Type of funding sources: None.

Background Doxorubicin (Dox) is a chemotherapeutic drug with cardiotoxicity as a severe side effect. Interestingly, Dox increases the expression of ceramide synthase 2 (CerS2) and increases long- chain ceramide levels with proinflammatory effects. Aim The purpose of our study was to identify the role of increased long- chain ceramides synthesized by CerS2 in Dox mediated cardiotoxicity in vitro and in vivo. Methods We incubated HL-1 cells (murine cardiomyocytes) with 0.7 μM Dox for 24h. In parallel cells were pretreated with fumonisin B (100 μM, 4h, FuB) to reduce Dox effects. We generated CerS2 ko mice and treated them with Dox and also generated doxycycline- inducible CerS2 mice. Expression of genes and proteins were measured with immunofluorescence (IF), western blot (WB) or qPCR. Ceramide levels were determined with mass spectrometry. Cellular staining was assessed by confocal laser scanning microscopy. Mitochondrial viability and activity were detected using seahorse analyzer. Results Protein expression measurement showed increased CerS2 level in vitro (2.4±0.32, p=0.03 for WB, 2.2±0.10, p Conclusion Our data show that Dox mediated cardiotoxicity is in part mediated by CerS2 and ceramides. CerS2 could be a valuable drug target for treatment of chemotherapy- associated cardiomyopathies. Funding Acknowledgement Type of funding sources: None. Immunofluorescence HL-1

Infective endocarditis (IE) is a life-threatening disease, caused by septic vegetations and inflammatory foci on the surface of the endothelium and the valves. Due to its complex and often indecisive presentation the mortality rate is still about 30%. Most frequently bacterial microorganisms entering the bloodstream are the underlying origin of the intracardiac infection. While the disease was primarily restricted to younger patients suffering from rheumatic heart streptococci infections, new at risk categories for Staphylococcus (S.) aureus infections arose over the last years. Rising patient age, increasing drug resistance, intensive treatment conditions such as renal hemodialysis, immunosuppression and long term indwelling central venous catheters but also the application of modern cardiac device implants and valve prosthesis have led to emerging incidences of S. aureus IE in health care settings and community. The aetiologic change has impact on the pathophysiology of IE, the clinical presentation and the overall patient management. Despite intensive research on appropriate in vitro and in vivo models of IE and gained knowledge about the fundamental mechanisms in the formation of bacterial vegetations and extracardiac complications, improved understanding of relevant bacterial virulence factors and triggered host immune responses is required to help developing novel antipathogenic treatment strategies and pathogen specific diagnostic markers. In this review, we summarize and discuss the two main areas affected by the changing patient demographics and provide first, recent knowledge about the pathogenic strategies of S. aureus in the induction of IE, including available experimental models of IE used to study host-pathogen interactions and diagnostic and therapeutic targets. In a second focus we present diagnostic (imaging) regimens for patients with S. aureus IE according to current guidelines as well as treatment strategies and surgical recommendations.

Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential. Therapy in NMS includes withdrawal of the causative medication and intensive care treatment possibly with administration of dantrolene.In this case report, we describe the clinical course of a 48 year old man who developed typical clinical symptoms and laboratory parameters of malignant hyperthermia syndrome after injection of haloperidol.

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Background Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) is increasingly used for treatment of severe cardiogenic shock, although it causes an increase in left ventricular (LV) afterload and might therefore hamper myocardial recovery. Recently, the addition of catheter-based left ventricular assist device (cLVAD) on top of VA-ECMO has been used to unload the LV and to improve outcome measures. However, there is limited data on predictors of outcome in this high-risk population. Aim The aim of this study was to evaluate predictors of 30-day survival in a multicentre cohort of severe cardiogenic shock patients treated with cLVADon top of VA-ECMO. Material and methods We report on consecutive patients from six tertiary care centers being treated with cLVAD in addition to VA-ECMO for treatment of cardiogenic shock. The primary endpoint is 30-day all-cause mortality. To identify predictors of the primary endpoint, multivariate analysis using an “elastic net” variable selection algorithm was done after imputation of missing variables. Results A total of 220 patients treated with cLVAD on top of VA-ECMO were included in the analysis. Of these, 79.1% were male with a median age of 55.5 (25thpercentile 48.0, 75thpercentile 65.6) years. In 60.5% of the patients, acute myocardial infarction was the underlying cause of cardiogenic shock and in 44.6% VA-ECMO was used for refractory cardiac arrest (eCPR). In the multivariable analysis, the following baseline parameters were significantly associated with the primary endpoint: Age (odds ratio of 1.68 per standard deviation), duration of cardiopulmonary resuscitation (OR 2.08 per SD), lactate (OR 1.04 per SD) and time from onset of shock to VA-ECMO (OR 1.30 per SD). Conclusion and outlook In this large-scale multicentre analysis of severe cardiogenic shock patients treated with VA-ECMO plus additional cLVAD unloading, age, duration of cardiopulmonary resuscitation, lactate and time from onset of shock to VA-ECMO were significantly associated with 30-day all-cause mortality. To further investigate this topic, we will evaluate predictors of outcome in distinct patient populations such as acute myocardial infarction vs. acute heart failure and patients without vs. patients with prior cardiopulmonary association.

Neuroleptic malignant syndrome (NMS) is a rare disorder caused by drug-induced dopamine-receptor-blockage or low dopamine concentration in the brain. It is a severe reaction to neuroleptic drugs in antipsychotic therapy. Symptoms in NMS typically consist of fever, muscle rigidity and cognitive changes; laboratory findings include elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis. To differentiate NMS from other malignant hyperthermia syndromes identifying the offending drug and clinical history are essential. Therapy in NMS includes withdrawal of the causative medication and intensive care treatment possibly with administration of dantrolene.In this case report, we describe the clinical course of a 48 year old man who developed typical clinical symptoms and laboratory parameters of malignant hyperthermia syndrome after injection of haloperidol.

Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable-adjusted associations between serum albumin and the rate of death after transplantation. The median follow-up time was 2.7 years. Those with severe (0.5–2.9 g/dL) and mild hypoalbuminemia (3.0–3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12–1.62) and 1.15 (95% CI: 1.04–1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1-year and overall mortality rate ratios were 1.48 (95% CI: 1.21–1.81) and 1.26 (95% CI: 1.11–1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.

Introduction: Diabetic cardiomyopathy (DbCM) contributes to the high risk of heart failure (HF) in diabetics, but mechanisms underlying DbCM remain unclear. We previously showed that highly saturated fat feeding in mice altered cardiomyocyte sphingolipid profiles leading to DbCM and that some of these maladaptations were dependent on autophagy and ceramide synthase 5 (CerS5). Hypothesis: In the present study, we sought to further understand the cellular processes in which lipid overload leads to DbCM in in the context of sphingolipids. Methods: Mice fed an obesogenic diet and in vitro studies using H9c2 cardiomyocytes were utilized in this study. Results: Increased oxidative stress and enhanced apoptosis were identified in the hearts of animals subjected to lipid overload, while animals treated with the sphingolipid synthesis inhibitor myriocin were protected. Similarly, cardiomyocytes treated with palmitate showed a sphingolipid-dependent increase of reactive oxygen species (ROS) and mitophagy. Treatment with mitochondria-targeted ceramide analogs induced cardiomyocyte cell death in an increasing chain length manner, which was exacerbated by inhibiting mitophagy. This suggested that lipotoxicity to cardiomyocytes occurs in part through oxidative stress in a sphingolipid-dependent manner, and mitophagy may occur to prevent further damage. Our observation that only longer chain ceramides led to these outcomes suggested involvement of CerS2 which specifically produces very long chain ceramides (C20 and higher). Overexpression of CerS2 showed increased mitophagy in cardiomyocytes and knockdown of CerS2 by CRISPR-CAS9 technology decreased mitophagy. Conclusions: Taken together, our data suggest that lipid overload induces mitophagy potentially as a protective measure in defense from CerS2-induced mitochondrial damage, oxidative stress and cell death in DbCM.

To investigate the correlation between the neuropathologic findings after laser-induced interstitial thermotherapy (LITT) and MRI temperature maps during laser irradiation, a total of six pig brains from cadavers were treated with a Nd:YAG laser (lambda = 1,064 nm, 3.8 W) for 15 minutes. For MRI monitoring, we used a phase-sensitive two-dimensional (2D) fast low-angle shot (FLASH) sequence on a 1.5-T Magnetom SP. Temperature maps were acquired every minute (accuracy

Laser-induced thermotherapy (LITT) is a minimally invasive neurosurgical approach to the stereotactic treatment of brain tumors in poorly accessible regions. Its clinical applicability has been shown in several experimental and clinical studies under on-line monitoring by magnetic resonance imaging (MRI). This review characterizes LITT as an alternative neurosurgical approach with specific focus on the typical histological alterations and ultrastructural cellular changes following laser irradiation in the central nervous system. The spatial and temporal pattern of these changes is discussed in their relevance to the neurosurgical treatment of neoplastic lesions using LITT.