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Aims Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS. Methods and results Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints. Conclusion In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy. Study registration number This study was registered in the PROSPERO (ID: CRD42021245477).

Cardiogenic shock is still a major driver of mortality on intensive care units and complicates ∼10% of acute coronary syndromes with contemporary mortality rates up to 50%. In the meantime, percutaneous circulatory support devices, in particular venoarterial extracorporeal membrane oxygenation (VA-ECMO), have emerged as an established salvage intervention for patients in cardiogenic shock. Venoarterial extracorporeal membrane oxygenation provides temporary circulatory support until other treatments are effective and enables recovery or serves as a bridge to ventricular assist devices, heart transplantation, or decision-making. In this critical care perspective, we provide a concise overview of VA-ECMO utilization in cardiogenic shock, considering rationale, critical care management, as well as weaning aspects. We supplement previous literature by focusing on therapeutic issues related to the vicious circle of retrograde aortic VA-ECMO flow, increased left ventricular (LV) afterload, insufficient LV unloading, and severe pulmonary congestion limiting prognosis in a relevant proportion of patients receiving VA-ECMO treatment. We will outline different modifications in percutaneous mechanical circulatory support to meet this challenge. Besides a strategy of running ECMO at lowest possible flow rates, novel therapeutic options including the combination of VA-ECMO with percutaneous microaxial pumps or implementation of a venoarteriovenous-ECMO configuration based on an additional venous cannula supplying towards pulmonary circulation are most promising among LV unloading and venting strategies. The latter may even combine the advantages of venovenous and venoarterial ECMO therapy, providing potent respiratory and circulatory support at the same time. However, whether VA-ECMO can reduce mortality has to be evaluated in the urgently needed, ongoing prospective randomized studies EURO-SHOCK (NCT03813134), ANCHOR (NCT04184635), and ECLS-SHOCK (NCT03637205). These studies will provide the opportunity to investigate indication, mode, and effect of LV unloading in dedicated sub-analyses. In future, the Heart Teams should aim at conducting a dedicated randomized trial comparing VA-ECMO support with vs. without LV unloading strategies in patients with cardiogenic shock.

Aims Patients with pulmonary hypertension (PHT) are often excluded from surgical therapies for tricuspid regurgitation (TR). Transcatheter tricuspid valve repair (TTVR) with the MitraClip™ technique is a novel treatment option for these patients. We aimed to assess the role of PHT in severe TR and its implications for TTVR. Methods and results A total of 243 patients underwent TTVR at two centres. One hundred twenty-one patients were grouped as iPHT+ [invasive systolic pulmonary artery pressures (PAPs) ≥50 mmHg]. Patients were similarly stratified according to echocardiographic PAPs (ePHT). The occurrence of the combined clinical endpoint (death, heart failure hospitalization, and reintervention) was investigated during a follow-up of 330 (interquartile range 175–402) days. iPHT+ patients were at higher preoperative risk (P Conclusion The discordant echocardiographic and invasive diagnosis of PHT in severe TR predicts outcomes after TTVR.

Background Lead-induced tricuspid regurgitation (TR) is a frequent complication after pacemaker- and ICD-implantation that is associated with increased mortality and hospitalizations. Purpose The aim of this pilot study was to investigate if lead implantation guided by transesophageal echocardiography (TEE) is feasible and might be able to reduce lead-associated TR. Methods 21 patients with indication for new pacemaker/ICD including a trans-tricuspid lead implantation and TR < grade 2+ were prospectively enrolled and underwent TEE-guided lead implantation in addition to fluoroscopy. Leads were placed according to a dedicated echo protocol with focus on a transgastric en face view of the tricuspid valve targeting a lead position in a tricuspid valve commissure (preferentially postero-septal) and an apical ventricular lead position. (Figure 1) Transthoracic echocardiography (TTE) was performed before implantation and at discharge. 121 consecutive patients with standard lead implantation guided by fluoroscopy only served as a historical control group. TR was assessed by an experienced cardiologist and graded according to current guidelines. Results Key baseline characteristics of overall 124 patients with a mean age of 74 years didn't differ between groups. Of note, there was no significant difference regarding device type and baseline TR. TEE-guided lead implantation was possible in all 21 patients in the TEE-group in deep conscious sedation without occurrence of serious adverse events. Lead placement in a commissure, mostly postero-septal, was possible in 95.2% of patients without worsening of TR (20/21 pts). Based on TEE-guidance, lead position or length was altered in 52.4% of patients (11/21 pts, 6 pts with lead repositioning, 5 pts with modification of lead length). Compared to baseline, the 21 patients in the TEE-group did not show worsening of TR at discharge. In contrast, TR worsening by one grade occurred in 13.6% of patients (14/103 pts) with new onset of TR ≥2+ in 6.8% of patients (07/103 pts) in the control group (p=0.001). At discharge, lead position was evaluated using 2D and 3D TTE in a subset of patients. In all examined patients (14/14 pts) lead position was unchanged compared to intraprocedural position and stable during inspiration vs. expiration as well as in upright vs. horizontal position. Conclusion TEE-guidance during PM/ICD-implantation was safe and feasible and resulted in steps to optimize lead position in a relevant number of patients. At discharge lead position remained stable and TEE-guided lead implantation was associated with less worsening of TR than standard lead implantation guided by fluoroscopy. Funding Acknowledgement Type of funding sources: None. TEE view with targeted lead position

Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. Funding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER

Background The outcome of patients with low-flow low-gradient (LFLG) aortic stenosis after transcatheter aortic valve replacement (TAVR) is not well evaluated. Long-term clinical success is thought to be less pronounced in LFLG patients compared to patients with high gradient (HG) aortic stenosis. Purpose The purpose of this study was to characterise different LFLG groups and determine their outcome after TAVR. We hypothesised that there would be relevant differences in baseline characteristics and patient survival after TAVR. Methods All patients undergoing TAVR for severe aortic stenosis at our centre between 2013 and 2019 were included in the study. Patients have been split into groups according preinterventional echocardiography data according to mean pressure gradient (dPmean), ejection fraction (EF), and stroke volume index (SVi). Patients with a dPmean Results 1,772 patients were analysed (mean follow-up 2.2 years, median age 81.7 [77.5–85.7] years) and split into groups: HG, 953 patients (54.3%), cLFLG, 446 patients (25.2%), and pLFLG 373 patients (21.1%). Baseline characteristics showed significant differences (p Rates of periprocedural complications including death, device failure, pericardial effusion, stroke or myocardial infarction were comparable between groups. Mortality rate (figure 1) was highest for cLFLG patients (43.4% [95% confidence interval, 37.3–48.6%]) compared to HG (25.1% [21.6–28.5%]) or pLFLG (32.9% [26.9–38.4%]), Log-rank test, Conclusion In this all-comer analysis, almost half of the patients belong toLFLG groups with considerable differences in patient characteristics. While equally safe during the procedure, patients with LFLG aortic stenosis show increased 3-year mortality rates compared to patients with HG aortic stenosis. Further studies evaluating this are needed. Funding Acknowledgement Type of funding sources: None. Figure 1. 3-year mortalityFigure 2. STS score-adjusted mortality

Aims The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. Methods and results Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2–5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57–1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47–1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01–4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18–2.56), P = 0.005], without interaction (P int = 0.76) between study groups. Conclusion Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

Background Transcatheter aortic valve replacement (TAVR) is the treatment of choice in most patients with severe aortic stenosis. The Society of Thoracic Surgeons (STS) score is a well established risk score to estimate morbidity, mortality and procedural risk of patients undergoing TAVR. However, tricuspid annular Dilatation (TAD), which is an increasingly recognized pathology associated with increased mortality, is not implemented in the STS Score. Purpose The purpose of this analysis was to investigate the incremental prognoctic value of TAD over the STS score. Methods Maximal septo-lateral diameter of the tricuspid annulus was measured in 923 patients on 3-dimensional MDCT datasets. A cut-off of 23 mm/m2 body-surface area was revealed by receiver-operating curve statistics and used to define TAD. Incremental prognostic Information was tested with c-index statistics and continuous net reclassification improvement (NRI). Patients were followed for 2 years and all-cause mortality was defined as study endpoint. Results Of 923 patients included in this analyis, TAD was found in 370 patients (40%). Patients with TAD had a significantly higher mortality (hazard ratio 2.18 with 95% CI 1.71 and 2.78, p4) and TAD. Estimated survival rates in patients with a low STS score and TAD and patients with a high STS score and no TAD were similiar (75.8% with 95% CI 68.9 and 83.5 and 74.8% with 95% CI 69.2 and 80.7, respectively). Kaplan-Meier curves are shown in Figure 1. Conclusion TAD is a common entity in patients undergoing TAVR for severe aortic stenosis. It is associated with significantly higher mortality and provides incremental prognostic Information over the STS score. Funding Acknowledgement Type of funding source: None

Aims To test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation. Methods and results We included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P Conclusion In post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.

Background Automated plaque quantification derived from coronary CT angiogragphy (CCTA) datasets provides exact and reliable assessment of coronary atherosclerosis burden. Purpose To investigate the long-term predictive value of quantified coronary plaque volume (PV) in comparison to Calcium Score (CACS). Methods Dedicated software was used to quantify PV in 1577 patients. A combination of cardiac death and acute coronary syndrome was used as endpoint. Incremental prognostic value was tested with c-statistics and continuous net reclassification improvement (NRI). The Morise Score was used to summarize patients clinical risk profile. Results Patients were followed for 10.4 years. The combined endpoint occurred in 59 patients, of whom 36 suffered from cardiac death, 18 had non-fatal myocardial infarction and 5 presented with unstable angina requiring revascularisation. The additive predictive value of PV and CACS was tested against a baseline model (c-index 0.741) including clinical risk and the number of diseased coronary segments (segment-Involvement score). While PV provided additive prognostic value (rise in c-index to 0.763, p=0.01 and NRI 0.247, p=0.03), CACS did not (c-index 0.749, p=0.2 and NRI 0.162, p=0.12). A threshold of 110.5 mm3, which was established by a previous analysis of our group, provided excellent separation of patients into low (no PV), intermediate (PV 110.5 mm3) risk categories based upon quantified PV (see attached Figure). Conclusion Quantification of PV from CCTA datasets provides excellent prognostic information on long-term follow-up.

Background/Introduction To date, no prehospital administered drug has shown to influence favourable neurological outcome in patients with out-of-hospital cardiac arrest (OHCA). Early administration of antiplatelet and anticoagulant medication might affect organ microcirculation and therefore favourable neurological outcome in the setting of OHCA. Purpose To evaluate the effect of prehospital acetylsalicylic acid and heparin (AH) administration on favourable neurological outcome and overall survival after OHCA in a large multicentre registry. Methods We examined patients with cardiac causes of OHCA that were prospectively included in the German Resuscitation Registry. Patients that were administered AH in the prehospital setting were matched in a 1:4 ratio with patients that were not administered AH. Pairs were matched for age >80 years, public place of collapse, initial ECG rhythm, witnessed by lay people and by emergency medical services (EMS), bystander CPR, usage of vasopressors, ECG signs of ACS or diagnosed ACS, coronary angiography conducted and hypothermia conducted. Analyses in the patients were stratified by treatment arm. Data was collected from 2011 to 2017 and analysed from January 2019 to March 2019. The primary endpoint was favourable neurological outcome at hospital discharge defined as cerebral performance category (CPC) 1 or 2. Secondary endpoints were return of spontaneous circulation (ROSC) as well as survival to hospital discharge. Logistic regression analysis and chi square analysis were used to evaluate the primary and secondary endpoints, respectively. Results Within the German Resuscitation Registry, 17,139 patients included between 2011 and 2017 had a presumably cardiac cause of OHCA with completed follow-up data. 205 patients were administered AH in the prehospital setting, whereas 16,934 were not. After matching in a 1:4 ratio, 174 patients in the AH group and 696 in the noAH group were suitable for analysis of the primary and the secondary endpoints. Prehospital AH administration was associated with favourable neurological outcome (OR for CPC 1 or 2 at hospital discharge 1.489 [1.026–2.162], p=0.036). Patients with AH were more likely to have ROSC (73.6% vs. 65.7% in the noAH group, p=0.047). Survival to hospital discharge was not statistically different between groups (32.8% vs. 28.5% in the noAH group). Consort flow-diagram Conclusion(s) In this matched-pair analysis, prehospital administration of AH was associated with an enhanced ROSC rate and with favorable neurological outcome. Randomized controlled trials are needed to confirm these results.

Background The TROPICAL-ACS trial showed that platelet function testing (PFT) guided de-escalation of P2Y12-inhibitor is a safe alternative treatment strategy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). No specific data are available on the efficacy of this strategy in patients with multivessel coronary artery disease (CAD). Purpose To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with multivessel CAD. Methods Two-thousand six-hundred-two biomarker-positive ACS patients were 1:1 randomized to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint (net clinical benefit) was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used log-rank statistics and Cox regression analysis with interaction testing to assess the effect of multivessel CAD on the primary and ischemic endpoints. Results Patients with multivessel (n=709) versus single-vessel CAD (n=1,901) exhibited a higher risk for the primary endpoint (10.2% vs. 7.6%; HR 1.36; 95% CI 1.02–1.81; p=0.034). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with single-vessel CAD (6.7% vs. 8.5%; pnon-inferiority = 0.001; Figure 1A) and multivessel CAD (9,5% vs. 10.9%; pnon-inferiority=0.041; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between single-vessel and multivessel CAD for both the primary (HR 0.78 [0.56–1.08]; p=0.137 in patients with single-vessel CAD vs. 0.86 [0.54–1.37; p=0.524 in patients with multivessel CAD; pinteraction=0.732) and combined ischemic endpoints (HR 0.80 [0.44–1.45]; p=0.456 in patients with single-vessel CAD vs. 0.71 [0.35–1. 46]; p=0.356 in patients with multivessel CAD; pinteraction=0.823). Kaplan-Meier curves Conclusion A guided de-escalation of P2Y12-inhibitor appears to be safe and effective in ACS patients with both single-vessel and multivessel CAD. Acknowledgement/Funding Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Background Tricuspid annular dilatation is an increasingly recognized entity associated with poor outcomes in patients with valvular heart disease, which led to upvaluation of tricuspid annuloplasty in current European and U.S. guidelines on valvular heart disease. Purpose To investigate the prognostic role of tricuspid annular dilatation measured in multi-slice CT (MDCT) datasets in patients undergoing transfemoral aortic valve replacement (TAVR). Methods All consecutive patients with available MDCT data undergoing TAVR at our institution between 2013 und 2016 were included. Maximal septal-lateral diameter was obtained from 3-dimensional MDCT datasets. Receiver-operating curves (ROC) analysis was performed to obtain an ideal cut-off for septal-lateral dilatation in systolic and diastolic heart phase. All-cause mortality served as endpoint. Results The study included 1137 patients, of whom 299 died within a mean follow-up period of 1.8±1 years. Mean patient's age was 80.6 years and 51.5% were women. TAVR was performed via transfemoral approach in all patients and balloon-expandable prosthesis were used in 69.4% of patients. ROC analysis revealed a cut-off of 45.7 mm for diastolic MDCT scans (n=859) and 36.1 mm for systolic MDCT scans (n=278). Patients above this threshold experienced a significantly higher mortality within the follow-up period (s. attached Figure, hazard ratio 1.63 with 95% CI 1.39 and 1.92, p Conclusion Tricuspid annular dilatation assessed with MDCT in patients undergoing TAVR is associated with 63% higher all-cause mortality. Future studies will have to determine whether interventional tricuspid annuloplasty techniques can reduce mortality in this group of patients.

Background Transcatheter edge-to-edge tricuspid valve repair (TTVR) is a novel treatment approach in heart failure patients with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk. Aim The aim of this study was to investigate the mean tricuspid valve gradient (TVG) over time and compare patient characteristics and outcome of patients with a post-procedure TVG of >3 mmHg vs. ≤3 mmHg. Methods All patients who were treated between between March 2016 and October 2018 with TTVR were included in this analysis. Trans-thoracic echocardiographic assessment of TVG was performed pre-procedurally, pre-discharge, after 1, 6, and 12 month. Results We treated 145 consecutive patients with moderate-to-severe secondary TR with TTVR. Patients were treated with TTVR for severe TR alone (70 patients) or in combination with mitral valve repair for concomitant severe mitral regurgitation and severe or moderate-severe TR with significant annulus dilatation (75 patients). One clip was implanted in 17 (11.7%), 2 clips in 83 (57.2%), 3 clips in 40 (27.6%) and 4 clips in 4 patients (2.8%). Reduction of at least 1 degree of TR was achieved in 136 Patients (93.8%). The median baseline TVG of all patients was 1 mmHg [Inter Quarter Range, IQR 1.0–1.4 mmHg]. The median TVG – measured at post-procedural trans-thoracic echocardiogram pre-discharge – increased to 2 mmHg [IQR, 1.6–3.0 mmHg] and remained constant up to 12 month (2.0 mmHg [IQR 1.0–2.0 mmHg). Of these, twenty-five patients showed an elevated TVG >3 mmHg post-procedurally. Patients with TVG >3 mmHg were younger (73.1±11.0 vs. 77.5±9.2 years, p=0.038) and presented with lower levels of pro-BNP at baseline (median 2276 ng/l [IQR, 906–5150] vs. 4182 ng/l [2310–8629], p=0.008) compared to patients with TVG ≤3mmHg. All other baseline characteristics were balanced. There were no differences in procedural success (TR reduction of ≥1 grade in 96% vs. 93.3%, p=0.946) and number of clips implanted (p=0.697). At one month follow-up there were no differences in NYHA class (NYHA class ≥3 in 24% vs. 30.8%, p=0.559), quality of life measured with the Minnesota Living With Heart Failure questionnaire (32.0±22.9 vs. 31.1±16.3, p=0.833), 6 minute walking distance (255.5±140.6 vs. 250.5±111.7 metre, p=0.872). The clinical endpoints 1-year mortality (HR 1.07; 95% CI [0.43–2.65], p=0.88) and the combined endpoint mortality and hospitalization for heart failure at one year (HR 1.07; 95% CI [0.46 to 2.48], p=0.88, see Figure) did not differ between patients with a TVG >3 mmHg vs. patients with a TVG ≤3mmHg. Figure 1 Conclusion TTVR results in a small increase in the tricuspid valve gradient, which remains constant up to one year. A small cohort of patients shows an elevated TVG higher than 3 mmHg after the procedure. This elevation has no impact on NYHA class at 1 month and the clinical endpoints mortality and hospitalization for heart failure at 1 year.

Background According to current recommendations, transcatheter aortic valve implantation (TAVI) should only be performed among patients with a life expectancy of at least one year. However, many deaths occur within the first year after TAVI. Purpose To assess the causes of death within one year after TAVI. Methods Data was taken between November 2007 and December 2017 from the EVERY-TAVI registry. Patients who died during TAVI or experienced mechanical complications requiring surgery were excluded from the analysis. We assessed the causes of death over 3 periods post-TAVI: within the first 30 days, between 30 and 90 days, and between 90 and 365 days. Results Overall, 2389 patients underwent TAVI without mechanical complications. Among them, 320 (1.3%) died within one year. Age was the main cause of death, accounting for 73 deaths (22.8%), followed by heart failure (20.6%) and infections (18.7%). During the first month, cardiogenic shock was the main cause of death (25.4%), followed by infections (22.2%) and terminal heart failure (20.6%), while age was responsible of only one death (1.6%). During the two following months, heart failure was the main cause of death (33.3%), followed by infections (21.2%), and the percentage of deaths due to age increased to 18.2%. After 3 months, age was the main cause of death (31.4%), followed by infection (16.8%) and heart failure (16.2%). Causes of death within one year of TAVI Cause of death All (n=320) 90 days (n=191) Older age, n (%) 73 (22.8) 1 (1.6) 12 (18.2) 60 (31.4) Terminal heart failure, n (%) 66 (20.6) 13 (20.6) 22 (33.3) 31 (16.2) Infection, n (%) 60 (18.7) 14 (22.2) 14 (21.2) 32 (16.8) Terminal renal failure, n (%) 26 (8.1) 4 (6.3) 5 (7.6) 17 (8.9) Cardiogenic shock, n (%) 26 (8.1) 16 (25.4) 4 (6.1) 6 (3.1) Malignancies, n (%) 18 (5.6) 0 (0.0) 2 (3.0) 16 (8.4) Sudden death, n (%) 17 (5.3) 6 (9.5) 2 (3.0) 9 (4.7) Stroke, n (%) 12 (3.7) 4 (6.3) 2 (3.0) 6 (3.1) Accident, n (%) 7 (2.2) 2 (3.2) 0 (0.0) 5 (2.6) Myocardial infarction, n (%) 7 (2.2) 2 (3.2) 2 (3.0) 3 (1.6) Non-cardiac surgery, n (%) 5 (1.6) 1 (1.6) 1 (1.5) 3 (1.6) Pulmonary embolism, n (%) 3 (0.9) 0 (0.0) 0 (0.0) 3 (1.6) Conclusion Cardiogenic shock is the main cause within the first month after TAVI, while older age is the main cause overall and after the initial months, highlighting the need to more carefully selection of patients undergoing TAVI.

Background A de-escalation of P2Y12-inhibitor treatment guided by platelet function testing (PFT) has been identified as a safe and alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, no specific data are available on the efficacy of such strategy in patients with high atherothrombotic risk (ATR). Purpose To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with low- vs. high-ATR. Methods The TROPICAL-ACS trial randomized 2,610 biomarker-positive ACS patients 1:1 to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used semi-parametric Cox regression analysis and interaction testing to assess the effect of low- vs. high-ATR on the primary and ischemic endpoints. High-ATR was defined as one of the following: (i) age ≥65 years or (ii) age Results Patients with high- (n=990) versus low-ATR (n=1,620) exhibited a higher risk for the primary endpoint (11.0% vs. 6.7%; HR 1.67; 95% CI 1.28–2.18; p Kaplan-Meier curves Conclusion A guided DAPT de-escalation strategy appears to be safe and effective in ACS patients regardless of the atherothrombotic risk. Further studies are needed for refining antiplatelet treatment strategies in ACS patients with varying levels of atherothrombotic risk. Acknowledgement/Funding Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Background Severe tricuspid regurgitation (TR) impairs right-ventricular forward stroke volume and left-ventricular preload leading to a reduction of cardiac output (CO). Transcatheter tricuspid valve repair (TTVR) is a novel experimental treatment strategy for TR and an alternative to surgery in fragile patients. The clinical impact of improved CO after TTVR on the prognosis of chronic heart failure patients is currently unknown. Purpose This study has been designed to analyze the impact of TTVR on CO and the association to post-interventional hospitalization for congestive heart failure (CHF) and all-cause mortality. Methods Between February 2017 and October 2018 we prospectively enrolled 70 patients suffering from chronic heart failure (median age 78 years; 54% female; 90% NYHA III or IV; median NT-pro-BNP of 3,540 ng/ml) due to severe TR (all ≥ grade 3 of 4). All patients underwent TTVR with isolated intervention to the tricuspid valve (n=41) or combined mitral and tricuspid intervention due to concomitant mitral regurgitation (n=29). Invasive CO was measured shortly before TTVR under general anesthesia using transpulmonary thermodilution. For a more physiologic assessment, non-invasive CO was measured using the inert gas rebreathing technique (Innocor, Innovision, Glamsbjerg, Denmark). Non-invasive CO was assessed 2 weeks prior TTVR (baseline), at the day of discharge from the hospital (post-procedural) and after a median of 193 days (interquartile range, IQR 53 to 360 days; follow-up). Results Invasive CO significantly correlated to non-invasive assessment of CO at baseline (Pearsons correlation coefficient r=0.36, p0.5 l/min in 33 patients (high ΔCO). Hospitalization for CHF was significantly lower with high ΔCO (18%), when compared to low ΔCO (54%; p Conclusion Successful TTVR with maintenance of improved CO impacts patient prognosis and is associated to a reduced rate of hospitalization and all-cause mortality.

Background Macrophages are the most abundant immune cells in the myocardial tissue in steady state. The sterile inflammation caused by myocardial infarction triggers a massive immune reaction, which leads to a profound influx of neutrophils and monocytes. In the postacute phase of infarction macrophages play an essential role in reparative processes. Recently, it has become clear that macrophages in the heart have a dual developmental origin from embryonic and bone marrow (BM) hematopoiesis. In this study, we sought to investigate the contribution of embryonic derived macrophages to the cardiac macrophage pool in steady state as well as the acute and chronic phase after ischemia/reperfusion injury. Methods/Results To address the origin of macrophages in steady state we used different models of lineage tracing to determine the developmental origin of cardiac macrophages. Using FLT3-Cre mice and radiation-independent CD45.1/.2 bone marrow chimera, we found that the resident macrophage population in the heart is mainly independent of definitive hematopoiesis (approximately 70–80% of cardiac macrophages). The BM-dependent population on the other hand is replenished by blood-derived monocytes. Further we used the radiation-independent CD45.1/.2 bone marrow chimera to characterize the origin of macrophages at different time points after I/R-injury. In the acute phase after myocardial infarction we observed a profound influx of BM-derived macrophages in the infarct region and also in the remote area. 30 days after I/R-injury the composition of the resident macrophage pool was mainly comprised of BM-independent macrophages, similar to steady state conditions. To address the role of BM-derived macrophages we used CCR2-ko mice, which have low numbers of inflammatory monocytes in peripheral blood. CCR2-ko mice showed reduced macrophage numbers in the acute phase after myocardial infarction. Using positron emission tomography we investigated the influence of CCR2-deficiency on cardiac function after I/R-injury. In comparison to WT mice, CCR2-ko mice showed a significantly increased infarct size. Cardiac remodeling, determined by end-diastolic volume, on the other hand was improved in CCR2-ko mice. The ejection fraction was similar in both groups. Conclusion The cardiac macrophage pool is mainly comprised of BM-independent macrophages. In response to I/R-injury monocyte-derived macrophages transiently enter the myocardium but do not persist in significant numbers over time. The influx of BM-derived macrophages after I/R-injury was reduced using CCR2-ko mice, which led to improved cardiac remodeling. Our findings are of potential importance for understanding the cardiac immune response and for the therapeutic targeting of macrophages in inflammatory conditions. Acknowledgement/Funding German Society of Cardiology, German Centre for Cardiovascular Research, LMU Excellence, SFB 914

Background Computed tomography (CT) imaging is considered as standard of care for transcatheter aortic valve replacement (TAVR) prothesis sizing. ECG-triggered high-pitch helical CT data acquisition on dual-source CT systems is associated with less contrast volumes, but CT image reconstruction of the aortic valve is limited to a single time point within the cardiac cycle. Although systolic CT imaging of the aortic valve is recommended due to the changes in aortic annulus area during the cardiac cycle, this recommendation is not supported by clinical outcome data. Purpose The study aimed to assess the impact of systolic vs. diastolic CT imaging of the aortic annulus for TAVR sizing on patient outcomes in a large series of patients. Methods In the study CT images of 1346 patients undergoing TAVR at our centre from 2013–2016 were re-evaluated. Patients were stratified into two groups with 0–35% and 36–99% of the RR-interval as systolic and diastolic CT imaging. Outcomes according to VARC2-criteria at 30 days and long-term survival were analysed. Results CTs of 1135 out of 1346 patients were analysed retrospectively, 278 (24.5%) of which were acquired during systole and 859 (75.5%) during diastole. Mean age was 80.6±7.6 years and 52.2% were female. Mean follow-up, available for 83.4% of patients, was 2.1±0.8 years. No significant difference in baseline characteristics was observed across both groups. Aortic annular area measurements were significantly larger in systole (mean aortic anulus area: systole: 4.8±1.0 cm2; diastole: 4.5±1.0 cm2, p There was no difference between groups concerning the combined endpoints for device success or early safety according to VARC2-criteria. Overall 30-day mortality was 3.4% (systole: 4.2% and diastole: 3.1%, p=0.35). Device failure occurred in 2.7% (systole: 2.9% and diastole: 2.7%, p=0.83). Permanent pacemaker implantation was required in 20.1% (systole: 18.7%, and diastole: 20.5%; p=0.55). Stroke rate at 30 days was 2.9%, n=33 and was similar in the two groups. The landmark analysis demonstrates the 30-day and 1-year mortality rates for both groups (Figure). Figure 1. Landmark analysis mortality Conclusion The current analysis does not suggest that systolic CT imaging for TAVR sizing is associated with improved early or late outcomes. Accordingly, full-cycle CT imaging which usually is associated with higher contrast volumes, should be avoided in this elderly population, which often presents with reduced kidney function.

Aims Guided de-escalation of P2Y12-inhibitor treatment was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. Safety and efficacy of this strategy may differ in relation to patient's age. This pre-specified analysis of the TROPICAL-ACS trial aimed to assess the impact of age on clinical outcomes following guided de-escalation of antiplatelet treatment in ACS patients. Methods and results Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). We used Cox regression models to assess the associations of age on clinical endpoints and interactions. In younger patients (age ≤70, n = 2240), the 1 year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to Bleeding Academic Research Consortium criteria) was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.51-0.96; P = 0.03, number needed to treat = 42]. In elderly patients (age >70, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; HR 1.17, 95% CI 0.69-2.01; P = 0.56). When the impact of age, as a continuous variable, was analysed on outcomes after guided de-escalation vs. control treatment, an increasing relative risk reduction was observed in the primary endpoint by decreasing age (Pint = 0.02), due to significant reductions in bleeding. Conclusion Treatment effects of guided de-escalation for P2Y12 inhibitors depend on patient's age with younger patients deriving a significant net clinical benefit. Although the safety and efficacy of guided de-escalation in the elderly was similar to uniform prasugrel therapy, this should be further investigated due to the limited sample size of this group.

Aims Alcohol is a risk factor for cardiac arrhythmias. Retrospective analyses suggest supraventricular arrhythmias consecutive to acute alcohol consumption, but prospective data are limited. We intended to prospectively associate acute alcohol consumption with cardiac arrhythmias. Methods and results At the 2015 Munich Octoberfest, we enrolled 3028 voluntary participants who received a smartphone-based ECG and breath alcohol concentration (BAC) measurements. ECGs were analysed for cardiac arrhythmias (sinus tachycardia, sinus arrhythmia, premature atrial/ventricular complexes, atrial fibrillation/flutter) and respiratory sinus arrhythmia. By multivariable adjusted logistic regression we associated BACs with cardiac arrhythmias. Similarly, we analysed 4131 participants of the community-based KORA S4 Study (Co-operative Health Research in the Region of Augsburg) and associated cardiac arrhythmias with chronic alcohol consumption. In our acute alcohol cohort (mean age 34.4 ± 13.3 years, 29% women), mean BAC was 0.85 ± 0.54 g/kg. Cardiac arrhythmias occurred in 30.5% (sinus tachycardia 25.9%; other arrhythmia subtypes 5.4%). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall (odds ratio (OR) per 1-unit change 1.75, 95% confidence interval (CI) 1.50–2.05; P Conclusions Acute alcohol consumption is associated with cardiac arrhythmias and sinus tachycardia in particular. This partly reflects autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday heart syndrome. ClinicalTrials.org accession number NCT02550340.

Aims In clopidogrel-treated patients undergoing coronary stenting, high on-treatment platelet reactivity was linked to a higher risk of stent thrombosis (ST). Platelet response to clopidogrel is significantly influenced by genetic factors. Recently published findings showed a highly significant impact of a common polymorphism (Q192R) within the paraoxonase-1 ( PON1 ) gene on clopidogrel treatment efficacy but no influence of the CYP2C19*2 genetic variant as previously demonstrated. The aim of this study was to assess the impact of the PON1 Q192R genotype in parallel to that of CYP2C19*2 on the antiplatelet effect of clopidogrel and the risk of ST in clopidogrel-treated patients. Methods and results In 1524 patients undergoing percutaneous coronary intervention, ADP-induced platelet aggregation was assessed in relation to PON1 Q192R and CYP2C19*2 genotypes. The clinical impact of genetic variants was investigated by comparing genotype frequencies of both genetic variants in a registry of 127 cases with early ST vs. an early ST-free control cohort ( n = 1439). For PON1 Q192R genotypes, platelet aggregation values were similar across all genotype groups ( P = 0.65). For CYP2C19*2 genotypes, significantly higher aggregation values were found in CYP2C19 wt/*2 and \*2/\*2 patients when compared with wt/wt allele carriers ( P < 0.0001). Comparing genotype frequencies between ST cases and controls, no differences were observed for PON1 Q192R genotype distributions ( P = 0.23), whereas the genotype distribution differed for CYP2C19*2 genotypes ( P = 0.019). Conclusion The PON1 Q192R genotype did not influence platelet response to clopidogrel or the risk of ST in clopidogrel-treated patients, whereas the CYP2C19*2 genotype impacted on both antiplatelet effect of clopidogrel and risk of coronary ST.