Abstract Background Access-related vascular and bleeding complications during transcatheter aortic valve implantation (TAVI) are associated with significant morbidity and mortality. Ultrasound-guided (USG) puncture may reduce the incidence of these events, particularly in large-bore arterial access. However, large-scale data on this approach are limited and it has not yet fully been implemented into standard clinical practice during TAVI. Purpose We compared access-related vascular and bleeding complications in USG versus fluoroscopy-guided (FG) access from a large multicenter TAVI registry. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 9,295 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. USG and FG access were performed in 1,992 (21.4%) and 7,303 (78.6%) patients, respectively. A propensity score was used to match 1,023 FG with 1,023 USG access patients in a 1:1 fashion. The primary endpoint was a composite of minor and major vascular complications at the TAVI-access site or bleeding type II-IV. Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Mean age was 81.9±6.25 years and 48.0% of patients were female. Comorbidities and clinical variables were well-balanced in matched groups. The overall risk profile was comparable in USG vs. FG (mean EuroSCORE II: 3.4 [2.1, 6.4] vs. 3.6 [2.2, 5.7], p=0.54). The primary end point occurred in 12.0% in the USG and 17.7% in the FG group, p<0.001. While major large bore access-related vascular complications did not differ significantly (3.5% vs. 4.2%, p=0.49), there was a trend towards lower minor complications for USG compared to FG (5.9% vs. 7.8%, p=0.096). Large bore access-related bleeding occurred in 5.5% versus 7.8% (p=0.04) of patients. Endovascular balloon inflation was required in 0.6% and 3.3% (p<0.001) of all large-bore access vascular complications. Stroke (1.7% vs. 1.5%, p=0.86) and stage III/IV acute kidney injury (3.0% vs. 2.2%, p=0.42) were similar in both groups. Conclusion In patients treated with transfemoral TAVI, ultrasound-guidance for gaining access was associated with lower rates of access-related vascular complications or type II-IV bleeding. Endovascular treatment was required more frequently in case of a fluoroscopy-guided approach. These findings challenge the fact that most TAVI procedures were performed with fluoroscopy-guidance.

Aims Heart failure‐related cardiogenic shock (HF‐CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute‐on‐chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute‐on‐chronic HF‐CS. Methods and results In this international observational study, patients with HF‐CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30‐day mortality, adjusted logistic/Cox regression models were fitted. Patients ( n = 1030) with HF‐CS were analysed, of whom 486 (47.2%) presented with de novo HF‐CS and 544 (52.8%) with acute‐on‐chronic HF‐CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute‐on‐chronic HF‐CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute‐on‐chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10–1.72, p = 0.005). Conclusion In this large HF‐CS cohort, acute‐on‐chronic HF‐CS was associated with more severe CS and higher mortality risk compared to de novo HF‐CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF‐CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

Abstract Background The transfemoral approach has become the gold standard primary access for transcatheter aortic valve implantation (TAVI) due to low complication rates. An additional secondary access (ScA) is used for angiographic guidance of the procedure. Recently, small, single-center studies demonstrated feasibility of single-access for transfemoral TAVI without a secondary access. However, comparative and large-scale data are missing. Purpose We assessed vascular and bleeding complications of ScA and Single access (SA) approaches in a large multicenter registry to evaluate both strategies. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. In 9,457 patients who qualified for analysis ScA (80.7% femoral, 19.3% radial) were performed in 8709 (92%) and SA in 748 (8%). Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Median age was 81.9[IQR 78.2, 85.1] years and 48.9% of patients were female (median logistic EuroSCORE II: 3.3% [IQR 2.1, 5.6]). Peripheral artery disease was comparable between groups (13.5 vs. 14.0%, p=0.73). While overall major access-related vascular complications did not differ significantly (6.1% vs. 4.8%, p=0.20), there was a higher incidence of minor complications for ScA compared to SA (9.0% vs. 2.8%, p<0.001). Secondary access complications amounted to 2.7% in the ScA group and were mainly characterized as bleeding (1.2%) and pseudoaneurysms (1.2%) mostly treated conservatively (1.2%), yet in some cases surgical repair was needed (0.8%). No significant difference was observed regarding type III/IV bleeding (4.1% vs. 4.3%, p=0.91), stroke rate (2.4% vs. 3.6%, p=0.05), stage III/IV acute kidney injury (2.4% vs. 2.4%, p=1.00) or all-cause 30-day mortality (5.8% and 5.7%, p=0.99) for ScA compared to SA groups. Conclusion In patients treated with transfemoral TAVI, a single access approach was associated with lower rates of minor access-related vascular complications without compromising overall outcomes, suggesting potential benefits of a minimally-invasive TAVI approach with the omission of additional vascular access.

Abstract Background High-sensitivity cardiac troponin (hs-cTn) is the laboratory gold-standard to diagnose myocardial infarction (MI). Yet, discrimination between different entities of myocardial injury, i.e. acute and chronic myocardial injury, and Type 1 (T1MI) versus Type 2 MI (T2MI), is still most challenging. Since, management of these entities is substantially different, there is an unmet clinical need for better discrimination. In clinical practice creatine-kinase (CK) is often used to decide whether patients with elevated hs-cTn concentrations are referred to primary invasive coronary angiography. However, it is unclear if the combined evaluation of CK and hs-cTn improves the discrimination between different types of myocardial injury, and MI. Objective Our aim was to evaluate, if the combination hs-cTnI with CK improves discrimination of acute versus chronic myocardial injury, and T1MI versus T2MI. Methods We included patients presenting with suspected MI to the emergency department of a tertiary center. CK and hs-cTnI (Architect STAT) were determined at presentation, and after 1h and 3h. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. STEMI patients were excluded from analyses. We calculated ratios of hs-cTnI and CK for each patient at each timepoint. Receiver-operator-curves with corresponding area under the curve (AUC) were used to assess the discriminative performance and compared with hs-cTnI alone. Logistic regression analysis was applied to calculate odds ratios (OR; 95% confidence intervals) for all ratios as well as hs-cTnI to distinguish T1MI vs T2MI, and chronic injury vs. any acute injury (acute myocardial injury, T1MI, T2MI). ORs are displayed using restricted cubic splines and values were entered log-transformed in the model. Results Of 3346 patients (median age 63 years, 36.4% women), 427 (12.8%) had MI, 103 (3.1%) had acute and 864 (25.8%) chronic injury. Log-transformed ratio of hs-cTnI/CK at presentation resulted in an AUC of 0.75 with an OR per SD for T1MI of 2.74 [2.14, 3.58], which was similar to hs-cTnI alone (AUC 0.76, p=0.75, OR per SD 3.07 [2.35, 4.09]). No significant differences were observed for measurements at 1h and 3h (Figure 1 A-C). Additionally, there was no improvement of discriminative performance regarding the discrimination of chronic and any acute myocardial injury by using hs-cTnI/CK ratios at any timepoint (AUCratio0h 0.77, AUChsTnI0h 0.8, p=0.17; ORratio0h per SD 3.44 [2.96, 4.02], ORhs-cTnI0h per SD 4.35 [3.66, 5.20]) (Fig. 1D-F). Restricted cubic splines show the overlapping correlation of increased propability for T1MI and any acute injury with higher hs-cTnI/CK ratios as well as hs-cTnI alone. (Figure 2). Conclusion The addition of CK to hs-cTnI does not improve discriminative capacity between patients with T1MI and T2MI, as well as between chronic and any acute myocardial injury compared to hs-cTnI alone.Figure 1:ROC curvesFigure 2:Natural cubic splines

Abstract Introduction Transthoracic bedside echocardiography (TTE) in the emergency department is recommended in patients with suspected myocardial infarction (MI), who do not qualify for early discharge using accelerated protocols. The prognostic value of routine echocardiographic parameters like wall motion abnormalities in patients with suspected MI, has not been evaluated so far. Therefore, our aim was to analyze whether TTE is a suitable risk stratification tool in patients presenting with suspected MI. Methods In a prospective cohort study, 2,719 patients presenting to the emergency department with symptoms indicate of MI were recruited. Patients with ST-segment elevation myocardial infarction (STEMI) and without available TTE were excluded. In the final dataset of 2,086 patients, pathological TTE-findings were defined as the composite of reduced systolic left ventricular(LV) function <50%, regional wall motion abnormalities (WMA) and severe valvular defects. Patients were followed up for up to 5 years to assess all-cause mortality and major adverse cardiac events (MACE), composited of cardiac rehospitalization, revascularization, MI excluding the index events, and death. Kaplan-Meier survival curves were created and compared using the log rank test. Cox-proportional hazard ratios with adjustment for age, sex, cardiovascular risk factors and high-sensitivity troponin were calculated for individual echocardiographic pathological findings. Results Among 2,086 patients 63.7% were male and the mean age was 64 years. Acute myocardial infarction was present in 308 (14.7%). 32.5% showed any pathological TTE-findings: A reduced systolic LV-function was detected in 18.6%, 18.4% had wall motion abnormalities, composed of 7.5% with akinesia and 10.9% with hypokinesia. Severe valvular defects were present in 7.8%. In patients with any pathological TTE-finding the rate of MACE was significantly higher than in patients without pathological findings (p<0.001, Figure 1A): After 5 years, MACE occurred in 320 (29.99%) of patients with a normal TTE, whereas 319 (59.65%) patients with at least one pathology developed MACE after 5 years. Overall mortality as a single component of the combined endpoint occurred in 86 (8.71%) patients with a normal TTE, while in patients with pathologies 152 (30.46%) had died (p<0.001, Figure 1B). Following cox-regression, valvular defects (HR 2,23 (95% CI 1,66-2,78)), highly reduced systolic LV-function <30% (HR 2,51 (95% CI 1,68-3,76)), and akinesia (HR 1,94 (95% CI 1,30-2,91)), were independent predictors of all-cause mortality at five years (Figure 2). Conclusion We describe the value of TTE as prognostic tool in patients with suspected MI and found that patients with pathologies in TTE were at substantially higher cardiovascular risk compared to patients without pathologies. Especially regional akinesia, highly reduced LV-function and severe valvular defects were strong predictors of mortality within 5 years.Kaplan-Meier survival curvesAdjusted cox-proportional hazard ratios

Abstract Introduction Patients with symptoms indicative of acute myocardial infarction (MI) frequently present to the emergency department (ED) and undergo a structured diagnostic assessment. Apart from MI, other diagnoses are frequently identified, including myocardial injury. In these patients estimation of long-term risk is crucial to guide preventive strategies. Purpose To assess and compare the long-term incidence of all-cause death and cardiovascular events in patients with MI, myocardial injury and other causes of acute chest pain. Methods We conducted a prospective, observational cohort study enrolling consecutive patients presenting with suspected MI to the ED of a tertiary hospital. The final diagnoses were adjudicated by two independent cardiologists according to the 4th Universal Definition of MI using high-sensitivity cardiac troponin T (hs-cTnT). Patients were followed to assess incidental all-cause death and a composite endpoint (cardiovascular death, MI, or myocardial revascularization). We used Kaplan-Meier plots for crude and Cox regression models (providing hazard ratios [95% confidence intervals]) for adjusted (sex, age, cardiovascular risk factors, heart failure, renal function) time-to-event analyses, respectively, using patients with other causes of chest pain as reference. Results Overall, we prospectively included 2,714 patients with a median age of 64 (25th, 75th: 51, 75) years, of whom 1,745 (64.3%) were male. In total, 143 (5.3%) had ST-elevation MI (STEMI), 128 (4.7%) Type 1 Non-ST-elevation MI (NSTEMI), 236 (8.7%) Type 2 NSTEMI, 86 (3.2%) acute myocardial injury, 677 (24.9%) chronic myocardial injury, and 1,444 (53.2%) other diagnoses of chest pain not involving hs-cTn elevation. The median follow-up time was 4.6 (4.5, 7.3) years. The highest rates of all-cause death were observed in patients with myocardial injury (81.6 [71.7, 92.3] events/1000 patient-years) and infarction (55.9 [46.3, 66.7]), compared to other diagnoses (12.2 (9.8, 15.1). Figure 1 provides the Kaplain-Meier estimates for the final diagnoses. In adjusted Cox regression analyses, all patients with MI or myocardial injury were at significantly higher risk for all-cause death, compared to patients with other causes of chest pain (Figure 2A). Additionally, the risk for the secondary composite endpoint (cardiovascular death, MI, revascularization) was significantly increased in those with acute or chronic myocardial injury, and patients with Type 1 NSTEMI or STEMI, but not Type 2 NSTEMI (Figure 2B). Conclusion Patients with acute myocardial infarction and acute or chronic myocardial injury are at high long-term risk for death and incident cardiovascular events. Importantly, those patients with acute myocardial injury showed the highest mortality rate. Further studies need to determine appropriate management strategies for patients with myocardial injury.Kaplan-Meier plot for final diagnosesForest plot of adjusted outcome analysis

Abstract Background Transcatheter aortic valve implantation (TAVI) has become the most common treatment for patients with severe aortic stenosis (AS) in Europe and North America. Current European guidelines recommend transfemoral TAVI for patients with severe, symptomatic AS aged ≥75 years. However, this cut-off is based solely on coincidentally existing patient cohort mean age of randomized controlled trials and individual risk factors might have a greater impact on outcomes after TAVI compared to age alone. Purpose This study aimed to validate the guideline-recommended age cut-off of 75 years compared to a comorbidity focused approach. Methods Using long-term prospective single-centre data, we analysed 4,278 patients with severe, symptomatic AS undergoing transfemoral TAVI between 2008-2022. A multivariable Cox regression model was fitted to assess predictors of all-cause mortality. Based on this model, a comorbid profile was defined as at least one prevalent comorbidity from the final model. Kaplan-Meier estimates were calculated for all-cause mortality after 3 years for young (<75 years) and elderly (≥75 years), and comorbid and non-comorbid patients. Results A total of 1,620 patients were included in the final analysis (<75 years: N=302 [18.6%], 70.8 [IQR 67.4-73.3] years; ≥75 years: N=1,318 [81.4%], 82.6 [IQR 79.5-85.6] years). In multivariable analysis, male gender (hazard ratio [HR] 1.37, 95%-confidence interval [CI] 1.06-1.77), atrial fibrillation (AF) (HR 1.78, 95%-CI 1.35-2.33), chronic obstructive pulmonary disease (COPD) (HR 1.44, 95%-CI 1.07-1.93) and chronic kidney disease (CKD) (eGFR <60ml/min/1.72m2) (HR 0.99, 95%-CI 0.98-0.99) were identified as predictors independently associated with all-cause mortality. Overall, 64% of patients were defined as comorbid by at least one risk factor emerging as an independent predictor: AF/COPD/CKD. While there was no difference in all-cause mortality between patients aged < or ≥75 years (27.5% vs. 23.9%, p=0.62) (Figure 1A), 3-year mortality rates were significantly higher in comorbid (30.4%) compared to non-comorbid subjects (14.5%, p<0.001) (Figure 1B). No difference was found comparing non-comorbid young to non-comorbid elderly (16.2% vs. 14.1%, p=0.69), but comorbid young showed higher mortality than non-comorbid elderly patients (34.0% vs. 14.1%, p<0.001) (Figure 1C). According to age-adjusted multivariable analysis, a comorbid risk profile was independently associated with all-cause mortality (HR 2.09, 95%-CI 1.49-2.93), whereas age was not predictive. Conclusion In a large all-comer TAVI patient cohort age was not predictive for mortality within a 3-year follow-up. This finding was true for both, non-comorbid as well as comorbid patients. Thus, outcome of patients with AS undergoing transfemoral TAVI depends on patients’ comorbidities rather than age. Our findings do not confirm the guideline recommended binary age cut-off currently recommended for patients with severe symptomatic AS.Figure 1

Abstract Introduction The diagnostic management of patients with symptoms indicative of acute myocardial infarction (MI) is largely based on the clinical assessment of symptoms, ECG and diagnostic algorithms based on high-sensitivity cardiac troponin (hs-cTn). Additionally, guidelines recommend transthoracic echocardiography (TTE) for patients neither eligible for rule-out nor rule-in. Purpose To assess the diagnostic performance of TTE in the diagnostic management of patients with suspected MI. Methods We conducted a prospective, observational cohort study enrolling consecutive patients presenting with symptoms suggestive of MI to the emergency department of a tertiary care hospital. Management was at the discretion of the treating physician. The final diagnosis was adjudicated by two independent cardiologists according to the 4th Universal Definition of MI. Evaluation in the emergency department included TTE with an assessment of left-ventricular (LV) function and regional wall motion abnormalities (WMA). We calculated diagnostic performance parameters (sensitivity, specificity, and negative and positive predictive value [NPV, PPV] with 95% confidence intervals) to rule-out or rule-in MI, respectively, for the presence of WMA. Performance was calculated for patients stratified to the observe and rule-in groups after application the ESC 0/1-hour algorithm using hs-cTnI. Patients without available TTE and those with STEMI were excluded. WMA were only reported if the acoustic window allowed a reasonable evaluation. Variables associated with the conduction of coronary angiography were studied using logistic regression. Results Overall, 2,163 patients with available TTE were included, of those 1,707 (78.9%) patients had data on WMA available, with 360 (21.1%) having any WMA (hypokinesia or akinesia) detected. Median age was 64 (51, 75) years, 1,383 (63.9%) were males and 383 (17.7%) were diagnosed with MI. Application of the ESC 0/1-hour algorithm resulted in assignment of 729 (42.9%) and 308 (18.6%) patients to the rule-out and -in groups, respectively, with 599 (38.5%) patients remaining in the observe group. Of these, 45 (7.5%) had MI. Performance of the ESC 0/1-hour algorithm was good and is shown in Figure 1. In the observe group, detection of WMA poorly identified patients with MI (PPV 12.7%, Figure 1). Absence of WMA resulted in moderate performance to rule-out MI (NPV 94.0%, Figure 1). Adjusted for age, sex, symptoms, baseline hs-cTnI, presence of ischemic signs on ECG and cardiovascular risk factors, the presence of WMA was significantly associated with the conduction of coronary angiography at index presentation (OR 2.7 [1.8, 4.0], p < 0.001). Conclusion The diagnostic value of bedside TTE is limited for the rule-out or -in of MI. Still, patients with prevalent WMA were significantly more likely to undergo coronary angiography.Performance of TTE in ESC 0/1-hour alg.

Abstract Background/Introduction Inflammation is recognized as a residual risk factor and mediator in patients with Atherosclerotic Cardiovascular Disease (ASCVD). High-sensitivity C-Reactive Protein (hsCRP), a marker of systemic inflammation, can be affected by modifiable risk factors (modRF). On the other hand, ASCVD and its extent might modify hsCRP levels. Data regarding the relationship between hsCRP, modRF and the extent of ASCVD remain scarce. Purpose We aimed to analyse the inflammatory burden in relation to the number of vascular beds affected by atherosclerosis and modRF in a contemporary large-scale population cohort. Methods After exclusion of individuals with inflammatory disorders, cancer, hsCRP concentrations >10 mg/L, missing hsCRP values and/or missing covariates 3,348 cases were left for analysis. Vascular beds affected were defined as coronary, peripheral and cerebrovascular atherosclerotic disease. ModRF were classified as follows: Lack of physical activity (PA) as <1.5 hours/week of exercise, a BMI ≥25 kg/m2 was considered as overweight, active smoking was defined as either current or quitted smoking within the last 6 months, and lastly poor adherence to a Mediterranean diet as a simple Mediterranean diet score (sMDS) of ≤2 points. Multivariable analyses were computed with hsCRP as dependent variable and modRF as covariates according to the number of vascular beds affected adjusting for age, sex, diabetes and intake of cholesterol-lowering drugs. Results Of the 3,348 participants at baseline 1,622 (48.1%) were female and mean age was 62 (1st, 3rd quartile: 54, 69) years. Concerning modRF 1,199 (39.5%) individuals showed low levels of PA, 1,877 (58.7%) were defined as overweight, poor adherence to MDS was determined in 1,421 (51.9%) participants and 694 (20.8%) were active smokers. Whilst no ASCVD was present in 1,612 (48.1%) participants, 1,134 (33.9%) and 602 (18.0%) individuals displayed atherosclerosis in 1 or ≥2 vascular beds, respectively. We found a stepwise increase of hsCRP levels with each incremental increase of modRF (median hsCRP for 0–4 modRF: 0.7, 0.9, 1.2, 1.5, 2.5 mg/L, respectively; p <0.05) and according to the number of vascular beds (median hsCRP for 0-≥2 vascular beds affected: 1.0, 1.1, 1.3 mg/L, respectively; p <0.05). The highest hsCRP concentration was found in individuals with atherosclerosis ≥2 beds and 4 modRF (Figure 1). In multivariable regression analyses, an independent association for increasing numbers of modRF with hsCRP levels across the extent of ASCVD was demonstrated (Table 1). Conclusion We demonstrate an increasing inflammatory burden according to the number of modRF and also with the presence and extent of ASCVD in a contemporary population-based cohort. These findings emphasize the important role of subclinical inflammation in the pathogenesis of ASCVD, and might be helpful for the definition of target populations for anti-inflammatory compounds across the extent of atherosclerotic disease.Figure 1Table 1