Evaluation of systemic inflammation in response to remote ischemic preconditioning in patients undergoing transcatheter aortic valve replacement (TAVR).

BACKGROUND: Systemic inflammation can occur after transcatheter aortic valve replacement (TAVR) and correlates with adverse outcome. The impact of remote ischemic preconditioning (RIPC) on TAVR associated systemic inflammation is unknown and was focus of this study. METHODS: We performed a prospective controlled trial at a single center and included 66 patients treated with remote ischemic preconditioning (RIPC) prior to TAVR, who were matched to a control group by propensity score. RIPC was applied to the upper extremity using a conventional tourniquet. Definition of systemic inflammation was based on leucocyte count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), assessed in the first 5 days following the TAVR procedure. Mortality was determined within 6 months after TAVR. RIPC group and matched control group showed comparable baseline characteristics. RESULTS: Systemic inflammation occurred in 66% of all patients after TAVR. Overall, survival after 6 months was significantly reduced in patients with systemic inflammation. RIPC, in comparison to control, did not significantly alter the plasma levels of leucocyte count, CRP, PCT or IL-6 within the first 5 days after TAVR. Furthermore, inflammation associated survival after 6 months was not improved by RIPC. Of all peri-interventional variables assessed, only the amount of the applied contrast agent was connected to the occurrence of systemic inflammation. CONCLUSIONS: Systemic inflammation frequently occurs after TAVR and leads to increased mortality after 6 months. RIPC neither reduces the incidence of systemic inflammation nor improves inflammation associated patient survival within 6 months.

The predictive role of early CRP values for one-year mortality in the first 2 d after acute myocardial infarction.

BACKGROUND: An excessive inflammatory reaction after acute myocardial infarction (AMI) is known to be harmful. New anti-inflammatory therapies are required. PURPOSE: This study assessed the predictive role of early CRP in patients with STEMI. METHODS: A total of 1003 patients with STEMI were analysed. A total of 180 patients with proven infection were excluded. CRP after 12, 24 and 48 h after pain onset were evaluated. RESULTS: Of 823 patients, 103 (12.5%) died within one year after AMI. The deceased patients showed higher CRP, even after already 12 h (6 vs. 13 mg/l, p < .001), 24 h (13 vs. 25 mg/l, p < .001) and after 48 h (40 vs. 92 mg/l, p < .001). A CRP of ≥8 mg/l, 12 h after AMI, was found in 45% and was independently associated with long-term mortality (OR: 2.7, p = .03), after 24 h: CRP ≥ 18 mg/l in 44% (OR: 2.5, p = .03), after 48 h: CRP ≥ 53 mg/l in 44% (OR 1.9, p = .03). Early CRP values correlated strongly with the later maximum value of CRP (p < .001). CONCLUSIONS: Already early CRP values are accurate for risk-prediction following AMI. By identifying patients who are beginning to develop an excessive inflammatory response, it may be possible to identify those who benefit from anti-inflammatory therapies.

The short term influence of right ventricular pacing burden on echocardiographic and spiroergometric parameters in patients with preserved left ventricular ejection fraction.

BACKGROUND: The incidence of worsened clinical outcome due to high right ventricular (RV) pacing burden in patients with preserved left ventricular function remains controversial. OBJECTIVE: To investigate the impact of RV pacing on several echocardiographic and spiroergometric parameters. METHODS: In 60 pacemaker patients with preserved left ventricular ejection fraction (LVEF) serial echocardiographies and spiroergometries were performed over a time course of 12 months. Additionally, in 48 patients retrospective echocardiographic analyses of the LV- and RV function were carried out up to 24 months after pacemaker implantation. RESULTS: The patients were divided into two groups: The high RV pacing burden group (hRVP: ≥ 40%) and the low RV pacing group (lRVP < 40%) according to the definitions in previous randomized MOST and DAVID trials. After a period of 12-month pacemaker therapy no changes to left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), LVEF, E/A-ratio; E/E'-ratio and tricuspid annular plane systolic excursion (TAPSE) could be revealed, independently of the RV pacing burden. Additionally, after 24-month long term follow-up there were no differences in LVEF and TAPSE in both groups. Accordingly, no relevant changes of peak exercise capacity, ventilatory anaerobic threshold or maximal oxygen consumption could be demonstrated independently of the RV pacing. CONCLUSIONS: In pacemaker patients with preserved LVEF the burden of RV pacing has no adverse influence on several echocardiographic and spiroergometric surrogate parameters of pacemaker-induced cardiomyopathy after a follow-up of 12 to 24 month. Despite this, screening for pacemaker induced cardiomyopathy should be performed especially in the presence of new heart failure symptoms.

Percutaneous Left Ventricular Assist Device Leads to Heart Rhythm Stabilisation in Cardiogenic Shock: Results from the Dresden Impella Registry.

BACKGROUND: Severe heart rhythm disturbances (SHRDs) occur regularly in cardiogenic shock (CS). Percutaneous left ventricular assist devices (pLVADs) can actively unload the left ventricle (LV), decreasing left ventricular end-diastolic pressure and wall tension, which are suspected parameters for the induction and maintenance of arrhythmias. The aim of this study was to describe effects of LV unloading on SHRD. METHOD: In the Dresden Impella Registry, 97 patients received an Impella CP in refractory CS. Of them, 19 had SHRDs, which were not stopped by common therapeutic strategies such as electrical defibrillation or antiarrhythmic drugs. They were only stopped after implantation of a micro-axial heart pump. This phenomenon was referred to as heart rhythm stabilisation (HRS). Clinical outcome and laboratory parameters were assessed and risk factors for the occurrence of HRS were identified. RESULTS: All 19 patients with refractory SHRD terminated immediately into a stable heart rhythm after insertion of the micro-axial heart pump. In 37% no additional defibrillation was needed. Of the patients with HRS, CS was mostly caused by myocardial infarction (68%). Resuscitation before pLVAD was performed in 89% for more than 30 minutes. Patients with HRS were resuscitated more frequently and for a longer duration than patients without HRS. After HRS, the serum lactate and norepinephrine dosage decreased in the first 12 hours, whereas left ventricular ejection fraction increased by 95%. CONCLUSIONS: Left ventricular unloading in patients with CS seems to be an option for treating patients with sustained life-threatening tachycardia, who are refractory to common treatment.

Regulation of circulating chromogranin B levels in heart failure.

BACKGROUND: Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF. METHODS AND RESULTS: We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair. CONCLUSION: CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.

Reduction of atrial fibrillation burden by pulmonary vein isolation leads to a decrease of CD11b expression on inflammatory cells.

Aims: It is hypothesized that inflammation could promote structural and electrical remodelling processes in atrial fibrillation (AF). Atrial infiltration of monocytes and granulocytes has been shown to be dependent on CD11b expression. The aim of this study was to investigate whether treatment of AF by pulmonary vein isolation (PVI) may lead to reduced inflammation, as indicated by a decrease of CD11b expression on monocytes and granulocytes. Methods and results: Flow-cytometric quantification analysis and determination of systemic inflammatory markers of peripheral blood were performed in 75 patients undergoing PVI 1 day before and 6 months after PVI. The extent of activation of monocytes and granulocytes was measured by quantifying the cell adhesion molecule CD11b. The mean expression of CD11b on monocytes (20.9 ± 2.5 vs. 10.2 ± 1.4; P < 0.001) and granulocytes (13.9 ± 1.6 vs. 6.8 ± 0.5; P < 0.001), as well as the relative count of CD11b-positive monocytes (P < 0.05) and CD11b-positive granulocytes (P < 0.01) were significantly reduced when comparing the identical patients before and 6 months after PVI. Systemic inflammatory parameters showed only a declining tendency after 6 months. Patients with unsuccessful PVI and ongoing AF on the day of follow-up showed no decrease in CD11b expression. Conclusions: A significant reduction of CD11b expression on monocytes and granulocytes, as a sign of reduced cellular inflammation, was achieved by treatment of AF using PVI. These data strongly support that AF is not only a consequence of but also a cause for inflammatory processes, which, in turn, may contribute to atrial remodelling.

Comparison of diverse platelet activation markers as indicators for left atrial thrombus in atrial fibrillation.

Atrial fibrillation (AF) is well known for being a major risk factor of thromboembolic stroke. We could recently demonstrate an association of monocyte-platelet aggregates (MPAs) with the degree of thrombogenicity in patients with AF. This study investigated platelet activation markers, as potential biomarkers for the presence of left atrial (LA) thrombus in patients with AF. One hundred and eight patients with symptomatic AF underwent transesophageal echocardiography (TEE) before scheduled cardioversion or pulmonary vein isolation. In order to determine the content of MPAs by flow-cytometric quantification analyses, blood was drawn on the day of TEE. The soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were obtained by Cytometric Bead Arrays (CBA). D-dimer levels were detected by quantitative immunological determination of fibrin degradation products. Clinical, laboratory, and echocardiographic standard parameters were obtained from all patients, including the determination of the flow in the left atrial appendage (LAA). Patients with detected LA thrombus (n = 28) compared with patients without thrombus (n = 80) showed an increased number of common risk factors, such as age, diabetes, heart failure, and coronary artery disease (CAD). The presence of LA thrombus was associated with significantly increased levels of MPAs (147 ± 12 vs. 304 ± 29 per µl; p < 0.00), sCD40L (106.3 ± 31.0 vs. 33.5 ± 2.1 pg/ml, p = 0.027), and D-dimer (0.13 ± 0.02 vs. 0.69 ± 0.21 mg FEU/l, p = 0.015). In contrast, sP-selectin showed no association with LA thrombus. A multivariate regression analysis showed that MPAs, sCD40L as well as D-dimers were independent indicators for the existence of LA thrombus. MPAs above 170 cells/µl indicated LA thrombus with a high sensitivity of 93% and a specificity of 73% (OR 62, 95% CI. 6.9-557.2, p < 0.001) in patients with AF, whereas the D-dimer lost their quality as independent indicator by using the conventional cut-off of 0.5 mg/l within the regression analysis. MPAs, as well as the D-dimer, correlated significantly negatively with the flow in the LAA measured during TEE. The content of MPAs, sCD40L, and D-dimer, but not sP-selectin showed an increased dependence on LA thrombus in patients with AF. In our study group, MPAs showed the best diagnostic test accuracy of the compared platelet markers. The different results of the examined platelet activation markers could be an indication of diverse mechanisms of LA thrombus in AF. Further studies should evaluate whether determination of MPAs in clinical routine may suffice to indicate the presence of LA thrombus in patients with AF.

Three-dimensional transoesophageal echocardiography is crucial for valid assessment of mitral valve leaflet morphology in severe mitral regurgitation prior to interventional repair.

BACKGROUND: Interventional mitral valve (MV) repair of severe symptomatic mitral regurgitation (MR) is a therapeutic option in high-risk surgical or inoperable patients. Assessment of the MV remains a crucial part of pre-interventional screening. Three-dimensional transoesophageal echocardiography (3D-TOE) may compensate for well-known pitfalls that occur in 2D-TOE. PURPOSE: We investigated whether the functional length of the central segments of the posterior and anterior MV leaflets (PML-P2 and AML-A2) is more reliably determined by 3D-TOE full volume datasets (3D-MPR) or orthogonal biplane-imaging (Xplane) when compared to 2D-TOE. METHODS AND RESULTS: Between February 2014 and August 2015, 265 consecutive patients with moderate to severe symptomatic MR were screened. Seventy patients were judged suitable for interventional MV repair by the in-house Heart-Team. Eventually, 59 patients remained for data analysis. Inter-observer variability was lowest in 3D-MPR followed by Xplane (r = 0.92 and 0.90, p < .001 for both) and highest in Mplane (r = 0.82, p < .001). Mean functional PML-P2 lengths were similar in Xplane (12.6 ± 1.7 mm) and 3D-MPR (12.1 ± 2.0 mm), however, significantly different in 2D-TOE (10.0 ± 2.1 mm, p < .001). 2D-TOE underestimated PML-P2 length with a bias of -2.5 mm compared to Xplane and -1.95 mm compared to 3D-MPR. In contrast, functional AML-A2 length was determined similar across all methods. CONCLUSIONS: Our results demonstrate the superiority of 3D-TOE over 2D-TOE for accurate MV assessment in MR, especially for the determination of the functional PML length. Erroneous MV leaflet assessment may result in inadequate therapy restriction if the MV is deemed not suitable for interventional repair.

Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death.

BACKGROUND: This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation. METHODS: From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers. Deidentified German patient data were used for a retrospective, nonrandomized analysis. RESULTS: Ninety-four patients (1.6%) were treated by the WCD in response to ventricular tachyarrhythmia/fibrillation. The incidence rate was 8.4 (95% confidence interval, 6.8-10.2) per 100 patient-years. Patients with implantable cardioverter-defibrillator explantation had an incidence rate of 19.3 (95% confidence interval, 12.2-29.0) per 100 patient-years. In contrast, an incidence rate of 8.2 (95% confidence interval, 6.4-10.3) was observed in the remaining cardiac diagnosis groups, including dilated cardiomyopathy, myocarditis, and ischemic and nonischemic cardiomyopathies. Among 120 shocked patients, 112 (93%) survived 24 hours after treatment, whereas asystole was observed in 2 patients (0.03%) with 1 resulting death. CONCLUSIONS: This large cohort represents the first nationwide evaluation of WCD use in patients outside the US healthcare system and confirms the overall value of the WCD in German treatment pathways.

Atheroprotective role of Caveolin-1 and eNOS in an innovative transplantation model is mainly mediated by local effects.

Endothelial dysfunction is crucial in the initiation of atherosclerosis, which is associated with a lack of nitric oxide. The endothelial NO synthase (eNOS) is responsible for constitutive synthesis of NO and inhibited by caveolin-1 (Cav1). In the current study, we examined the influence on intima formation through single and combined deletion of eNOS and Cav1 with a focus on differentiation of local and systemic effects. A sex-mismatch transplantation of denudated aortae from female C57BL/6n (WT), Cav1-/-, eNOS-/- and Cav1-/-/eNOS-/- (C/e--/--) mice in common carotid artery of male WT mice was performed. After six weeks on Western-type diet, the aortae were explanted and intimal lesions were quantified by determining the intima-media-ratio (IMR). Significantly larger plaques were observed in all knockout mice compared to WT. The highest IMR was detected in Cav1-/- arteries associated with an increased expression of α-smooth muscle actin (αSMA) and the proliferating cell nuclear antigen (PCNA). Both were reduced in aortae from C/e--/--. Galectin-3 (Gal3) immunostaining revealed only small infiltrations of macrophages. Systemic cell invasion was detected by Y chromosome fluorescence in situ hybridization (Y-FISH), which showed only small numbers of systemic cells and no differences between the genotypes. Loss of Cav1 increased vascular lesion by enhancing neointimal proliferation. The combined loss of Cav1 and eNOS, compared to Cav1-/-, lowered intima formation, suggesting an increasing effect of eNOS in the absence of Cav1 on vascular lesion. Furthermore, these effects seem to be mediated by local cells rather than by systemically invaded ones.

Association of platelet activation markers with recurrence of atrial fibrillation after pulmonary vein isolation.

Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.

Troubleshooter in electrical storm: Mechanical unloading leads to heart rhythm stabilization.

The electrical storm is a life-threatening situation which causes a complex antiarrhythmic treatment. We firstly report a rhythmological stabilization through mechanical unloading of the left ventricle in a health patient who developed electrical storm after endo- and epicardiac re-ablation and who previously underwent 27 unsuccessful defibrillations. No evidence for a specific etiology of the rhythm disturbances was found. After implantation of a percutaneous left ventricular assist device (pLVAD) a single additional defibrillation was needed to terminate ventricular fibrillation. This unique application of pLVAD might be an unprecedented escape strategy for patients who have exhausted all other commonly recommended therapy options.

Aortic stenosis: right and left ventricular function in the early postprocedural phase. Comparison between transcatheter and surgical aortic valve implantation.

BACKGROUND: While impact of surgical aortic valve replacement (SAVR) on the function of the right and left ventricle (RV, LV) has been studied extensively, the objective of this study was to compare the two different transcatheter approaches, transfemoral vs. transapical aortic valve implantation (tf-AVI, ta-AVI) and SAVR with respect to postoperative recovery of RV and LV function in patients with severe aortic stenosis. METHODS AND RESULTS: Conventional echocardiographic studies were performed before and after the procedure (< 8 days) in 74 consecutive patients undergoing tf-AVI, 88 with ta-AVI and 63 surgically treated patients. Post procedure, a marked deterioration in the tricuspid annular plane systolic excursion (TAPSE) was seen after SAVR (23.7 +/- 4 mm vs. 15.6 +/- 2.9 mm, P > 0.001) and ta-AVI (21.1 +/- 4.7 mm vs. 19.1 +/- 4.7 mm, P = 0.02), while TAPSE remained unchanged in the tf-AVI group (21.7 +/- 5 mm vs. 22.1 +/- 4.9 mm, P = 0.38). Additionally, a significant drop of the visually estimated right ventricular ejection fraction in the SAVR and ta-AVI group compared to tf-AVI could be seen (P < 0.001, P = 0.003, respectively) Among patients with a pre-existing reduced LV-function, despite similar baseline LVEF (38.5 +/- 7.1% vs. 37.4 +/- 5.6, P = 0.8), tf-AVI patients had better recovery of LVEF compared with ta-AVI (ALVEF 7.2 +/- 8% vs. 1.6 +/- 9.3%, P = 0.038). CONCLUSION: Our study underlines the less invasive nature of tf-AVI, causing less intraoperative trauma and pericardial adhesions to the heart. Given that acute RV failure after cardiac surgery remains a major cause of morbidity and mortality, the results of the present study suggest that in high-risk patients, TAVI and in particular tf-AVI could be favoured over SAVR in regard to a RV dysfunction.

Chronic diarrhea as the initial clinical manifestation of light-chain amyloidosis with cardiac involvement despite negative duodenal and rectal biopsies.

Early and accurate diagnosis and a prompt initiation of treatment are critical for the prognosis of light-chain amyloidosis. The present article describes a case involving a 62-year-old patient who experienced unexplained, chronic diarrhea with negative duodenal and rectal biopsies. Serum immunofixation, a free light-chain assay, electrocardiography and echocardiography were performed after the patient developed syncope. The results of these diagnostic investigations showed characteristic signs of systemic amyloidosis. Cardiac and bone marrow biopsies confirmed the diagnosis of systemic light-chain amyloidosis. The chronic diarrhea was found to be due to an autonomic neuropathy of the enteric nervous system.

Benefit of 3D Vena Contracta Area over 2D-Based Echocardiographic Methods in Quantification of Functional Mitral Valve Regurgitation.

BACKGROUND: The two-dimensional proximal isovelocity surface area (2D PISA) method in the quantification of an effective regurgitation orifice area (EROA) has limitations in functional mitral valve regurgitation (FMR), particularly in non-circular coaptation defects. OBJECTIVE: We aimed to validate a three-dimensional vena contracta area (3D VCA) against a conventional EROA using a 2D PISA method and anatomic regurgitation orifice area (AROA) in patients with FMR. METHODS: Both 2D and 3D full-volume color Doppler data were acquired during consecutive transoesophageal echocardiography (TEE) examinations. The EROA 2D PISA was calculated as recommended by current guidelines. Multiplanar reconstruction was used for offline analysis of the 3D VCA (with a color Doppler) and AROA (without a color Doppler). Receiver operating characteristic (ROC) analysis was used to calculate a cut-off value for the 3D VCA to discriminate between moderate and severe FMR as classified by the EROA 2D PISA. RESULTS: From 2015 to 2018, 105 consecutive patients with complete and adequate imaging data were included. The 3D VCA correlated strongly with the 2D PISA EROA and AROA (r = 0.93 and 0.94). In the presence of eccentric or multiple regurgitant jets, there was no significant difference in correlations with the 3D VCA. We found a 3D VCA cut-off of 0.43 cm2 to discriminate between moderate and severe FMR (area under curve = 0.98). The 3D VCA showed a higher interobserver agreement than the EROA 2D PISA (interclass correlation coefficient: 0.94 vs. 0.81). CONCLUSIONS: The 3D VCA has excellent validity and lower variability than the conventional 2D PISA in FMR. Compared to the 2D PISA, the 3D VCA was not affected by the presence of eccentric or multiple regurgitation jets or non-circular regurgitation orifices. With a threshold of 0.43 cm2 for the 3D VCA, we demonstrated reliable discrimination between moderate and severe FMR.

Imaging Predictors of Left Ventricular Functional Recovery after Reperfusion Therapy of ST-Elevation Myocardial Infarction Assessed by Cardiac Magnetic Resonance.

BACKGROUND: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. RESULTS: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = -0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = -0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = -0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. CONCLUSION: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI.

Myeloid PHD2 deficiency accelerates neointima formation via Hif-1α.

The key players of the hypoxic response are the hypoxia-inducible factors (Hif), whose α-subunits are tightly regulated by Prolyl-4-hydroxylases (PHD), predominantly by PHD2. Monocytes/Macrophages are involved in atherosclerosis but also restenosis and were found at hypoxic and sites of the lesion. Little is known about the role of the myeloid PHD2 in atherosclerosis and neointima formation. The study aimed to investigate the consequences of a myeloid deficiency of PHD2 in the process of neointima formation using an arterial denudation model. LysM-cre mice were crossed with PHD2fl/fl, PHD2fl/fl/Hif1αfl/fl and PHD2fl/fl/Hif2αfl/fl to get myeloid specific knockout of PHD2 and the Hif-α subunits. Denudation of the femoral artery was performed and animals were fed a western type diet afterwards with analysis of neointima formation 5 and 35 days after denudation. Increased neointima formation in myeloid PHD2 knockouts was observed, which was blunted by double-knockout of PHD2 and Hif1α whereas double knockout of PHD2 and Hif-2α showed comparable lesions to the PHD2 knockouts. Macrophage infiltration was comparable to the neointima formation, suggesting a more inflammatory reaction, and was accompanied by increased intimal VEGF-A expression. Collagen-content inversely correlated to the extent of neointima formation suggesting a destabilization of the plaque. This effect might be triggered by macrophage polarization. Therefore, in vitro results showed a distinct expression pattern in differentially polarized macrophages with high expression of Hif-1α, VEGF and MMP-1 in proinflammatory M1 macrophages. In conclusion, the results show that myeloid Hif-1α is involved in neointima hyperplasia. Our in vivo and in vitro data reveal a central role for this transcription factor in driving plaque-vascularization accompanied by matrix-degradation leading to plaque destabilization.

Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device.

Background: The APACHE II score assesses patient prognosis in intensive care units. Different disease entities are predictable by using a specific factor called Diagnostic Category Weight (DCW). We aimed to validate the prognostic value of the APACHE II score in patients treated with a percutaneous left ventricular assist device because of refractory cardiogenic shock (CS). Methods: From the Dresden Impella Registry, we analyzed 180 patients receiving an Impella CP®. The main outcome was the observed intrahospital mortality ( S ^ ( t h o s p ) ), which was compared to the predicted mortality estimated by the APACHE II score. Results: The APACHE II score, which was 33.5 ± 0.6, significantly overestimated intrahospital mortality ( S ^ ( t h o s p ) 54.4 ± 3.7% vs. APACHE II 74.6 ± 1.6%; p < 0.001). Nevertheless, the APACHE II score showed an acceptable accuracy to predict intrahospital mortality (ROC AUC 0.70; 95% CI 0.62-0.78). Thus, we adapted the formula for calculation of predicted mortality by adjusting DCW. The total registry cohort was randomly divided into derivation group for calculation of adjusted DCW and validation group for testing. Intrahospital mortality was much more precisely predicted using the adjusted DCW compared to the conventional DCW (difference of predicted and observed mortality: -4.7 ± 2.4% vs. -23.2 ± 2.3%; p < 0.001). The new calculated DCW was -1.183 for the total cohort. Conclusion: The APACHE II score has an acceptable accuracy for the prediction of intrahospital mortality but overestimates its total amount in CS patients. Adjustment of the DCW can lead to a much more precise prediction of prognosis.

Simple periprocedural precautions to reduce Doppler microembolic signals during AF ablation.

BACKGROUND: Doppler microembolic signals (MES) occur during atrial fibrillation ablation despite of permanent flushed transseptal sheaths, frequent controls of periprocedural coagulation status and the use of irrigated ablation catheters PURPOSE: To investigate the number and type of MES depending on the procedure time, prespecified procedure steps, the activated clotting time (ACT) during the ablation procedure and the catheter contact force. METHODS: In a prospective trial, 53 consecutive atrial fibrillation patients underwent pulmonary vein isolation by super-irrigated "point-by-point" ablation. All patients underwent a periinterventional, continuous transcranial Doppler examination (TCD) of the bilateral middle cerebral arteries during the complete ablation procedure. RESULTS: An average of 686±226 microembolic signals were detected by permanent transcranial Doppler. Thereby, 569±208 signals were differentiated as gaseous and 117±31 as solid MES. The number of MES with regard to defined procedure steps were as follows: gaseous: [transseptal puncture, 26 ± 28; sheath flushing, 24±12; catheter change, 21±11; angiography, 101±28; mapping, 9±9; ablation, 439±192; protamine administration, 0±0]; solid: [transseptal puncture, 8±8; sheath flushing, 9±5; catheter replacement, 6±6; angiography, not measurable; mapping, 2±5; ablation, 41±22; protamine administration, 0±0]. Significantly less MES occurred with shorter procedure time, higher ACT and the use of tissue contact force monitoring. CONCLUSION: The current study demonstrates that during atrial fibrillation ablation using irrigated, "point-by-point" RF ablation, masses of microembolic signals are detected in transcranial ultrasound especially in the period of RF current application. The number of MES depends on the total procedure time and the reached ACT during ablation. The use of contact force monitoring might reduce MES during RF ablation.

Data for validation and adjustment of APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device.

A precise prognosis is of imminent importance in intensive care medicine. This article provides data showing the overestimation of intrahospital mortality by APACHE II score in various subgroups of cardiogenic shock patients treated with a percutaneous left ventricular assist device. The data set includes additional baseline characteristics regarding age, pre-existing diseases, characteristics of coronary artery disease, characteristics of cardiopulmonary resuscitation, and hemodynamic parameter not included in the APACHE II score. Further data were provided which characterize derivation and validation group. Both groups were used for adjustment of the APACHE II approach. The data are supplemental to our original research article titled "Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device" (Mierke et al., IJC Heart & Vasculature. 40 (2022) 101013. https://doi.org/10.1016/j.ijcha.2022.101013).