Cardiac Magnetic Resonance Imaging Versus Computed Tomography to Guide Transcatheter Aortic Valve Replacement: A Randomized, Open-Label, Noninferiority Trial.

BACKGROUND: Computed tomography (CT) is recommended for guiding transcatheter aortic valve replacement (TAVR). However, a sizable proportion of TAVR candidates have chronic kidney disease, in whom the use of iodinated contrast media is a limitation. Cardiac magnetic resonance imaging (CMR) is a promising alternative, but randomized data comparing the effectiveness of CMR-guided versus CT-guided TAVR are lacking. METHODS: An investigator-initiated, prospective, randomized, open-label, noninferiority trial was conducted at 2 Austrian heart centers. Patients evaluated for TAVR according to the inclusion criteria (severe symptomatic aortic stenosis) and exclusion criteria (contraindication to CMR, CT, or TAVR, a life expectancy <1 year, or chronic kidney disease level 4 or 5) were randomized (1:1) to undergo CMR or CT guiding. The primary outcome was defined according to the Valve Academic Research Consortium-2 definition of implantation success at discharge, including absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance. Noninferiority was assessed using a hybrid modified intention-to-treat/per-protocol approach on the basis of an absolute risk difference margin of 9%. RESULTS: Between September 11, 2017, and December 16, 2022, 380 candidates for TAVR were randomized to CMR-guided (191 patients) or CT-guided (189 patients) TAVR planning. Of these, 138 patients (72.3%) in the CMR-guided group and 129 patients (68.3%) in the CT-guided group eventually underwent TAVR (modified intention-to-treat cohort). Of these 267, 19 patients had protocol deviations, resulting in a per-protocol cohort of 248 patients (121 CMR-guided, 127 CT-guided). In the modified intention-to-treat cohort, implantation success was achieved in 129 patients (93.5%) in the CMR group and in 117 patients (90.7%) in the CT group (between-group difference, 2.8% [90% CI, -2.7% to 8.2%]; P<0.01 for noninferiority). In the per-protocol cohort (n=248), the between-group difference was 2.0% (90% CI, -3.8% to 7.8%; P<0.01 for noninferiority). CONCLUSIONS: CMR-guided TAVR was noninferior to CT-guided TAVR in terms of device implantation success. CMR can therefore be considered as an alternative for TAVR planning. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03831087.

Improved detection of echocardiographically occult left ventricular thrombi following ST-elevation myocardial infarction.

AIM: The aim of this study was to investigate predictors of transthoracic echocardiography (TTE)-occult left ventricular (LV) thrombi (LVT) and to propose a clinical model for improved detection of TTE-occult LVT post-ST-elevation myocardial infarction (STEMI). Patients with acute STEMI are at significant risk for developing LVT. However, this complication often (up to 65%) remains undetected by using TTE, referred to as TTE-occult LVT. METHODS AND RESULTS: In total, 870 STEMI patients underwent TTE and cardiac magnetic resonance (CMR), the reference method for LVT detection, 3 days after infarction. Clinical (body mass index, peak cardiac troponin T) and echocardiographic [ejection fraction, apical wall motion scores (AWMSs)] predictors were analysed. Primary endpoint was the presence of TTE-occult LVT identified by CMR imaging. From the overall cohort, 37 patients (4%) showed an LVT by CMR. Of these thrombi, 25 (68%) were not identified by TTE. Transthoracic echocardiography-occult thrombi did not significantly differ in volume (1.4 vs. 2.74 cm3), diameter (19.0 vs. 23.3 mm), and number of fragments or shape compared with TTE-apparent LVT (all P > 0.05). For predicting these TTE-occult LVT, the 16-segment AWMS (AWMS16Seg) showed highest validity {area under the curve: 0.91 [95% confidence interval (CI): 0.89-0.93]; P < 0.001}, with an association independent of ejection fraction and 17-segment AWMS (AWMS17Seg) [odds ratio: 1.68 (95% CI: 1.43-1.97); P < 0.001] and clinical (body mass index, peak troponin) and angiographic (culprit lesion, post-interventional thrombolysis in myocardial infarction flow) associates of TTE-occult LVT (all P < 0.05). Dichotomization at AWMS16Seg ≥ 8 (n = 260, 30%) allowed for a detection of all TTE-occult LVT (sensitivity: 100%), with a corresponding specificity of 77%. CONCLUSION: After acute STEMI, AWMS16Seg served as a simple and very robust predictor of TTE-occult LVT. An AWMS16Seg-based algorithm to identify patients for additional CMR imaging offers great potential to optimize detection of TTE-occult LVT following STEMI.

Benefit of extracorporeal membrane oxygenation in myocardial infarction-induced cardiogenic shock.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is frequently used for emergency support in patients with profound cardiogenic shock (CS) of all etiologies. However, no controlled study investigating ECMO in myocardial infarction (AMI)-induced CS is available. METHODS: Retrospective analysis of patients experiencing AMI induced CS; ECMO therapy vs. non ECMO therapy. A total of 476 patients with AMI-induced CS were investigated. One hundred twenty-seven patients (26.7%) received emergency veno-arterial ECMO support, 349 patients did not receive ECMO support. Patients were propensity score matched based on relevant clinical and laboratory factors and revealed 127 matched pairs. RESULTS: Mean age of patients was 65.0±12.3 years and mean Syntax score was 25.9±7.3 in the full unmatched patient population. Survival at 1, 3 and 5 years after CS was 45.6%, 43.5%, and 41.3% in the ECMO group and 17.4%, 15.8%, and 14.9% in the full unmatched control group (log-rank: P<0.001). After propensity score matching, 1-, 3-, and 5-year survival was 14.4%, 13.5%, and 11.2% in the matched control group (P<0.001). Cox regression analysis identified ECMO support (HR: 2.57; 95% CI: 1.89-3.50; P<0.001) and completeness of revascularization (HR: 1.89; 95% CI: 1.74-2.34, P=0.003) to be independent predictors for long term survival. CONCLUSIONS: Extracorporeal life support by ECMO significantly increased survival in patients with AMI-induced CS. ECMO insertion increased survival probability 2.57-fold and should be considered as first line treatment in patients with profound AMI-induced CS.

Determinants and prognostic relevance of aortic stiffness in patients with recent ST-elevation myocardial infarction.

The association between aortic stiffness, cardiovascular risk factors and prognosis in patients with recent ST-elevation myocardial infarction (STEMI) is poorly understood. We analyzed the relationship between cardiovascular risk factors and arterial stiffening and assessed its prognostic significance in patients with recent STEMI. We prospectively enrolled 408 consecutive patients who sustained a first STEMI and underwent primary percutaneous coronary intervention (PPCI). Aortic pulse wave velocity (PWV), the most widely used measure of aortic stiffness, was determined by the transit-time method using velocity-encoded, phase-contrast cardiac magnetic resonance imaging. Patient characteristics were acquired at baseline and major adverse cardiac and cerebrovascular events (MACCE) were assessed at 13 [interquartile range (IQR) 12-31] months. Cox regression- and logistic regression analysis were performed to explore predictors of aortic stiffness and MACCE. Median aortic PWV was 6.6 m/s (IQR 5.6-8.3 m/s). In multivariable analysis, age [odds ratio (OR) 1.10, 95% confidence interval (CI), 1.08-1.14, p < 0.001] and hypertension (OR 2.45, 95% CI, 1.53-3.91, p < 0.001) were independently associated with increased PWV. Sex, diabetes, smoking status, dyslipidemia, and obesity were not significantly associated with PWV in adjusted analysis (all p > 0.05). High PWV significantly and independently predicted occurrence of MACCE in adjusted analysis [hazard ratio (HR) 2.45, 95% CI 1.19-5.04, p = 0.014]. In patients with recent STEMI, the impact of classical cardiovascular risk factors on aortic stiffness is mainly dependent on age and increased blood pressure. Increased aortic stiffness is associated with adverse clinical outcome post-STEMI, suggesting it as a relevant therapeutic target in this population. Trial (NCT04113356).

Association of plasma interleukin-6 with infarct size, reperfusion injury, and adverse remodelling after ST-elevation myocardial infarction.

AIMS: Little is known about the clinical relevance of interleukin (IL)-6 in patients with acute ST-elevation myocardial infarction (STEMI). This study examined the possible associations of plasma IL-6 concentrations with infarct size (IS), reperfusion injury and adverse left ventricular remodelling (LVR), in STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: We prospectively included 170 consecutive STEMI patients (median age 57 years, 14% women) treated with primary PCI between 2017 and 2019. Blood samples for biomarker analyses including IL-6 were collected on Day 2. Left ventricular ejection fraction (LVEF), IS, and reperfusion injury [microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH)] were determined using cardiac magnetic resonance (CMR) imaging on Day 4. Left ventricular remodelling was defined as ≥10% increase in left ventricular end-diastolic volume from baseline to 4 months CMR follow-up. Patients with IL-6 concentrations ≥median (17 ng/L) showed a significantly lower LVEF (43% vs. 52%, P < 0.001), larger IS (22% vs. 13%, P < 0.001), larger MVO (1.9% vs. 0.0%, P < 0.001), and more frequent IMH (52% vs. 18%, P < 0.001). Left ventricular remodelling was more common in patients with IL-6 ≥ median (24% vs. 9%, P = 0.005). In both linear and binary multivariable regression analyses, IL-6 remained independently associated with lower LVEF [odds ratio (OR): 0.10, 95% confidence interval (CI) 0.02-0.42, P = 0.002], larger IS (OR: 5.29, 95% CI 1.52-18.40, P = 0.009), larger MVO (OR: 5.20, 95% CI 1.30-20.85, P = 0.020), with presence of IMH (OR: 3.73, 95% CI 1.27-10.99, P = 0.017), and adverse LVR (OR: 2.72, 95% 1.06-6.98, P = 0.038). CONCLUSIONS: High concentrations of circulating plasma IL-6 on Day 2 after STEMI were independently associated with worse myocardial function, larger infarct extent, more severe reperfusion injury, and a higher likelihood for LVR, suggesting IL-6 as a useful biomarker of more serious outcome and potential therapeutic target. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04113356;NCT04113356.

Association of C-Reactive Protein Velocity with Early Left Ventricular Dysfunction in Patients with First ST-Elevation Myocardial Infarction.

C-reactive protein velocity (CRPv) has been proposed as a very early and sensitive risk predictor in patients with ST-elevation myocardial infarction (STEMI). However, the association of CRPv with early left ventricular (LV) dysfunction after STEMI is unknown. The aim of this study was to investigate the relationship between CRPv and early LV dysfunction, either before or at hospital discharge, in patients with first STEMI. This analysis evaluated 432 STEMI patients that were included in the prospective MARINA-STEMI (Magnetic Resonance Imaging In Acute ST-elevation Myocardial Infarction. ClinicalTrials.gov Identifier: NCT04113356) cohort study. The difference of CRP 24 ± 8 h and CRP at hospital admission divided by the time (in h) that elapsed during the two examinations was defined as CRPv. Cardiac magnetic resonance (CMR) imaging was conducted at a median of 3 (IQR 2-4) days after primary percutaneous coronary intervention (PCI) for the determination of LV function and myocardial infarct characteristics. The association of CRPv with the CMR-derived LV ejection fraction (LVEF) was investigated. The median CRPv was 0.42 (IQR 0.21-0.76) mg/l/h and was correlated with LVEF (rS = -0.397, p < 0.001). In multivariable linear as well as binary logistic regression analysis (adjustment for biomarkers and clinical and angiographical parameters), CRPv was independently associated with LVEF (ß: 0.161, p = 0.004) and LVEF ≤ 40% (OR: 1.71, 95% CI: 1.19-2.45; p = 0.004), respectively. The combined predictive value of peak cardiac troponin T (cTnT) and CRPv for LVEF ≤ 40% (AUC: 0.81, 95% CI 0.77-0.85, p < 0.001) was higher than it was for peak cTnT alone (AUC difference: 0.04, p = 0.009). CRPv was independently associated with early LV dysfunction, as measured by the CMR-determined LVEF, revealing an additive predictive value over cTnT after acute STEMI treated with primary PCI.

Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.

BACKGROUND: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. METHODS: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. FINDINGS: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. INTERPRETATION: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. FUNDING: Austrian Science Fund and German Center for Cardiovascular Research.

C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction.

BACKGROUND: The role of C-reactive protein velocity (CRPv) as an early and sensitive marker of an excessive inflammatory response in the setting of acute ST-elevation myocardial infarction (STEMI) is only poorly understood. The aim of this study was to investigate, in patients with STEMI treated with primary percutaneous coronary intervention (PCI), the association of CRPv with microvascular infarct pathology. METHODS AND RESULTS: This prospective cohort study included a total of 316 patients with STEMI undergoing PCI. CRPv was defined as the difference between CRP 24 ± 8 h and CRP at hospital admission, divided by the time (in h) that have passed during the two examinations. The association of biomarker levels with cardiac magnetic resonance (CMR)-determined microvascular obstruction (MVO) was evaluated. CMR was performed at a median of 3 [interquartile range 2-4] days after PCI. After adjustment for cardiac troponin T (cTnT), anterior infarction and TIMI flow pre and post-PCI, CRPv (odds ratio 2.70, 95% confidence interval (CI) 1.54-4.73; p = 0.001) remained significantly associated with the occurrence of MVO. CRPv (area under the curve [AUC] 0.76, 95% CI 0.71-0.81; p < 0.001) was a better predictor for MVO compared to 24 h CRP (AUC difference: 0.03, p = 0.002). The addition of CRPv to peak cTnT resulted in a higher AUC for MVO prediction than peak cTnT alone (AUC 0.86, 95% CI 0.82-0.90; p < 0.001 vs. AUC 0.84, 95% CI 0.79-0.88; p < 0.001. AUC difference: 0.02, p = 0.042). CONCLUSIONS: In patients with STEMI treated with primary PCI, CRPv was associated with microvascular infarct pathology with a predictive value incremental to cTnT, suggesting CRPv as an early and sensitive biomarker for more severe infarct pathology and outcome.

Estimating the extent of myocardial damage in patients with STEMI using the DETERMINE score.

BACKGROUND: Recently, a simple ECG score (DETERMINE score) has been proposed for estimating myocardial scar in patients with ischaemic cardiomyopathy. We sought to evaluate the usefulness of the DETERMINE score for the assessment of myocardial infarct size (IS) as well as microvascular obstruction (MVO), in the setting of ST-elevation myocardial infarction (STEMI). METHODS: This observational study enrolled 423 patients with STEMI (median age 56, 17% women), revascularised by primary percutaneous coronary intervention (PCI). For evaluation of the DETERMINE and Selvester scoring system (an established but complex ECG score for IS estimation), ECG was conducted before discharge (median: 4 (IQR 2-6) days). Cardiac magnetic resonance (CMR) was conducted within a week after infarction for determination of IS and MVO. RESULTS: Median DETERMINE score of the overall cohort was 8 points (IQR 5-11). A higher DETERMINE score was significantly associated with a larger IS (21% vs 11% of left ventricular myocardial mass (LVMM), p<0.001) as well as larger MVO (1.2% vs 0.0% of LVMM, p<0.001). In linear and binary multivariable logistic regression analysis, the DETERMINE score remained independently associated with IS (OR 1.09, 95% CI 1.02 to 1.17, p=0.014) and MVO (OR 1.12, 95% CI 1.04 to 1.21, p=0.003), after adjustment for Selvester score and clinical indicators of IS (high-sensitivity cardiac troponin T, high-sensitivity C reactive protein, N-terminal pro-B-type natriuretic peptide, TIMI flow pre-interventional and post-interventional PCI, anterior infarct localisation). CONCLUSIONS: In patients undergoing PCI for STEMI, the DETERMINE score provides an easy and inexpensive tool for appropriate estimation of infarct severity as determined by CMR.

Cardiac magnetic resonance imaging improves prognostic stratification of patients with ST-elevation myocardial infarction and preserved ejection fraction.

Aims: To evaluate the prognostic validity of clinical risk factors as well as infarct characterization and myocardial deformation by cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients with preserved left ventricular ejection fraction (LVEF) following primary percutaneous coronary intervention (PCI). Methods and results: This multicentre, individual patient-data analysis from two large CMR trials included 1247 STEMI patients. Cardiac magnetic resonance examinations were conducted 3 [interquartile range (IQR) 2-4] days after PCI. LVEF, infarct size, microvascular obstruction (MVO), and myocardial strain values were measured. Primary endpoint was defined as composite of major adverse cardiovascular events (MACE) including death, re-infarction, and congestive heart failure. A preserved LVEF (defined as LVEF ≥50%) was observed in 724 patients (=58%). In the overall cohort, 97 patients experienced a MACE event [follow-up time 12 (IQR 12-13) months], and 34 MACE events occurred in the group with preserved LVEF (5% vs. 12% incidence rate in patients with LVEF < 50%). TIMI risk score [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.02-1.59; P = 0.03] and female gender (HR 2.24, 95% CI 1.10-4.57; P = 0.03) emerged as independent clinical determinants of MACE in the patient group with preserved LVEF. Among CMR parameters, the presence of MVO (HR 2.39, 95% CI 1.05-5.46; P = 0.04) and reduced global longitudinal strain (GLS; HR 1.12, 95% CI 1.02-1.23; P = 0.02) independently predicted MACE in the LVEF-preserved population. The addition of MVO and GLS to the clinical prognostic markers (TIMI risk score, female gender) increased (P = 0.02) the prognostic validity [AUC 0.76 (95% CI 0.73-0.79)] compared to the clinical markers alone [AUC 0.65 (0.62-0.69)]. Conclusion: In contemporary treated STEMI patients showing preserved LVEF, a CMR-based risk prediction approach assessing MVO and GLS provided strong prognostic value that was incremental to clinical outcome parameters.

Association of Myocardial Injury With Serum Procalcitonin Levels in Patients With ST-Elevation Myocardial Infarction.

Importance: Myocardial tissue injury due to acute ST-elevation myocardial infarction (STEMI) initiates an inflammatory response that leads to a release of systemic inflammatory biomarkers, including C-reactive protein (CRP) and white blood cells, consequently reducing the usefulness of these routine biomarkers for identifying concomitant infections. The clinical role of procalcitonin (PCT), a promising marker of bacterial infection, to detect concomitant infection in acute STEMI is unknown, mainly because it is unclear whether myocardial injury per se induces systemic PCT release. Objective: To investigate the release of serum PCT in the acute setting of STEMI (24 and 48 hours after primary percutaneous coronary intervention) and to elucidate any associations with myocardial injury markers through a comprehensive assessment by cardiac magnetic resonance (CMR) imaging. Design, Setting, and Participants: This prospective cohort study conducted between 2016 and 2018 included 141 consecutive patients with STEMI treated with primary percutaneous coronary intervention. Concentrations of PCT, high-sensitivity CRP (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) and white blood cell counts were measured serially 24 and 48 hours after infarct. Exposures: Acute STEMI and primary percutaneous coronary intervention. Main Outcomes and Measures: The association of PCT and typical inflammatory marker levels with CMR-determined myocardial damage was assessed. Infarct size, extent of microvascular obstruction, and occurrence of intramyocardial hemorrhage as determined by CMR within the first week following STEMI were also evaluated. Results: In total, 141 patients with STEMI (117 men [83%]) having a median age of 56 years (interquartile range, 50-66 years) were included. The median PCT concentration was 0.07 µg/L (interquartile range, <0.06-0.11 µg/L) 24 hours after intervention and 0.07 µg/L (interquartile range, <0.06-0.09 µg/L) 48 hours after intervention. Whereas hs-CRP and hs-cTnT levels and white blood cell counts were significantly correlated with CMR markers of myocardial damage at both 24 and 48 hours after intervention, the PCT level showed no significant correlation with infarct size (at 24 hours: r = 0.07; P = .40; at 48 hours: r = 0.13; P = .12) or with microvascular obstruction (at 24 hours: r = -0.03; P = .75; at 48 hours: r = 0.09; P = .30). Furthermore, PCT levels at 24 hours (odds ratio, 1.25; 95% CI, 0.63-2.48; P = .52) and 48 hours (odds ratio, 1.56; 95% CI, 0.72-3.41; P = .26) were not significantly associated with the presence of intramyocardial hemorrhage. Conclusions and Relevance: In the acute phase after percutaneous coronary intervention for STEMI, circulating PCT levels remained unassociated with the extent of myocardial and microvascular tissue damage as visualized by CMR imaging.

Extracorporeal Life Support in Myocardial Infarction-Induced Cardiogenic Shock: Weaning Success.

BACKGROUND: Outcome data of patients with acute myocardial infarction (AMI)-induced cardiogenic shock (CS) receiving extracorporeal life support (ECLS) are sparse. METHODS: A consecutive series of 106 patients with AMI-induced CS receiving ECLS was evaluated regarding ECLS weaning success, hospital mortality, and long-term outcome. The Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) risk score was applied, and multivariable Cox regression analysis was performed. RESULTS: Mean patient age was 58.2 ± 11.2 years, and 78.3% were men. In 34 patients (32.1%), ECLS was implemented during ongoing cardiopulmonary resuscitation. De novo AMI was present in 58 patients (54.7%), and percutaneous coronary intervention complications were causative among 48 patients (45.3%). Multivessel coronary artery disease was diagnosed among 73.6% with mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores of 30.8 ± 4.8. Actuarial survival was 54.4% at 30 days, 42.2% at 1 year, and 38.0% at 5 years and was significantly higher among patients with low and intermediate IABP-SHOCK II risk scores at ECLS onset (log-rank P = .017). ECLS weaning with curative intention after a mean perfusion time of 6.6 ± 5.1 days was feasible in 51 patients (48.1%) and more likely among patients with complete revascularization (P = .026). Multivariable Cox regression analysis identified complete revascularization (hazard ratio, 2.38; 95% confidence interval, 1.1 to 5.1; P = .028) and absence of relevant mitral regurgitation at ECLS discontinuation (hazard ratio, 2.71; 95% confidence interval, 1.2 to 6.0; P = .014) to be associated with beneficial long-term survival after ECLS discontinuation. CONCLUSIONS: Emergency ECLS is a valuable option among patients with AMI-induced CS with low and intermediate IABP-SHOCK II risk scores. ECLS weaning is manageable, but additional revascularization of all nonculprit lesions is mandatory after ECLS implementation.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

BACKGROUND: Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. METHODS: In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. RESULTS: Patients with left ventricular remodeling (n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). CONCLUSIONS: Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

Driving ability after right-sided puncture of the common femoral artery during coronary angiography.

OBJECTIVES/BACKGROUND: To assess brake reaction time (BRT; key factor in driving ability) in patients receiving transfemoral coronary angiography (CAG). We assumed that patients would have a significantly impaired BRT after the procedure. METHODS: A prospective, observational study design was applied. Consecutive patients undergoing right-sided transfemoral CAG as part of the clinical routine were included. An experimental driving simulator was used to determine BRT after receiving a visual stimulus. The subjects applied the brake with their right foot as quickly as possible when a red-light signal appeared. The time interval between stimulus and brake application was taken as BRT. In addition to the total BRT, also its components were determined: neurologic reaction time, foot transfer time and brake travel time. BRT was determined before and 1 day after CAG (pre-post comparison). RESULTS: 71 patients were included in the analysis (58 male, age 61 ± 9 years). Total BRT was 594 ± 188 and 591 ± 198 ms before and after the CAG procedure, respectively (p = 0.270). Similarly, also the BRT components 'foot transfer time' and 'brake travel time' did not show significant differences between the two test occasions. However, neurologic reaction time decreased from 269 ± 67 to 255 ± 64 ms (p = 0.036). CONCLUSIONS: We found no impairment of BRT on the first day after puncture of the right-sided femoral artery in patients undergoing CAG. Therefore, with regard to BRT, it is regarded safe to resume driving from day 1 after CAG. Other factors of driving safety beyond BRT must also be considered.

Sitagliptin Accelerates Endothelial Regeneration after Vascular Injury Independent from GLP1 Receptor Signaling.

INTRODUCTION: DPP4 inhibitors (gliptins) are commonly used antidiabetic drugs for the treatment of type 2 diabetes. Gliptins also act in a glucose-independent manner and show vasoregenerative effects. We have shown that gliptins can remarkably accelerate vascular healing after vascular injury. However, the underlying mechanisms remain unclear. Here, we examined potential signaling pathways linking gliptins to enhanced endothelial regeneration. METHODS AND RESULTS: We used wild-type and GLP1 receptor knockout (Glp1r-/-) mice to investigate the underlying mechanisms of gliptin-induced reendothelialization. The prototype DPP4 inhibitor sitagliptin accelerated endothelial healing in both animal models. Improved endothelial growth was associated with gliptin-mediated progenitor cell recruitment into the diseased vascular wall via the SDF1-CXCR4 axis independent of GLP1R-dependent signaling pathways. Furthermore, SDF1 showed direct proproliferative effects on endothelial cells. Excessive neointimal formation was not observed in gliptin- or placebo-treated Glp1r-/- mice. CONCLUSION: We identified the SDF1-CXCR4 axis as a crucial signaling pathway for endothelial regeneration after acute vascular injury. Furthermore, SDF1 can directly increase endothelial cell proliferation. Gliptin-mediated potentiation of endothelial regeneration was preserved in Glp1r-/- animals. Thus, gliptin-mediated endothelial regeneration proceeds through SDF-1/CXCR4 in a GLP1R-independent manner after acute vascular injury.

Femoral access site closure without prior femoral angiography : A retrospective analysis.

AIMS AND BACKGROUND: Although guideline recommendations have shifted towards a transradial route, femoral puncture is still an established vascular access, especially for complex coronary interventions. The FemoSeal™ vascular closure device (FVCD) helps to reduce femoral compression time and access site complications after removal of the catheter sheath. To ensure safe use, an angiography of the femoral artery prior to FVCD deployment is recommended by the manufacturer. We postulate that omitting this angiography does not relevantly increase the risk for vascular complications. METHODS AND RESULTS: In this retrospective analysis of an all-comers population (n = 1923) including patients receiving a percutaneous coronary intervention (PCI), we could show that combined vascular complication rates without femoral angiography were low (primary endpoint 4.6%) and comparable to a randomized clinical trial that did perform angiography of the vascular access site in a cohort of patients receiving diagnostic coronary angiography only. In addition to this analysis, we could demonstrate that patients with an acute coronary syndrome, receiving periprocedural anticoagulation or anti-platelet therapy had an increased risk for the formation of arterial pseudoaneurysms; however, we did not observe any ischemic vascular event after FVCD deployment. CONCLUSION: Closure of the femoral access site after coronary angiography using the FVCD can be safely performed without femoral angiography; however, due to an increased risk for the formation of pseudoaneurysms we recommend the transradial access in situations with increased bleeding risk.

Reversal of tumor acidosis by systemic buffering reactivates NK cells to express IFN-γ and induces NK cell-dependent lymphoma control without other immunotherapies.

Like other immune cells, natural killer (NK) cells show impaired effector functions in the microenvironment of tumors, but little is known on the underlying mechanisms. Since lactate acidosis, a hallmark of malignant tissue, was shown to contribute to suppression of effective antitumor immune responses, we investigated the impact of tissue pH and lactate concentration on NK-cell functions in an aggressive model of endogenously arising B-cell lymphoma. The progressive loss of IFN-γ production by NK cells observed during development of this disease could be ascribed to decreased pH values and lactate accumulation in the microenvironment of growing tumors. Interestingly, IFN-γ expression by lymphoma-derived NK cells could be restored by transfer of these cells into a normal micromilieu. Likewise, systemic alkalization by oral delivery of bicarbonate to lymphoma-developing mice was capable of enhancing IFN-γ expression in NK cells and increasing the NK-cell numbers in the lymphoid organs where tumors were growing. By contrast, NK-cell cytotoxicity was dampened in vivo by tumor-dependent mechanisms that seemed to be different from lactate acidosis and could not be restored in a normal milieu. Most importantly, alkalization and the concomitant IFN-γ upregulation in NK cells were sufficient to significantly delay tumor growth without any other immunotherapy. This effect was strictly dependent on NK cells.