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Purpose Recurrent stroke is considered to increase the incidence of severe disability and death. For correct risk assessment and patient management it is essential to identify the origin of stroke at an early stage. Transthoracic echocardiography (TTE) is the initial standard of care for evaluating patients in whom a cardioembolic source of stroke (CES) is suspected but its diagnostic capability is limited. Transesophageal echocardiography (TEE) is considered as gold standard; however, this approach is time consuming, semi-invasive and not always feasible. We hypothesized that adding a delayed-phase cardiac computed tomography (cCT) to initial multimodal CT might represent a valid alternative to routine clinical echocardiographic work-up. Material and Methods Patients with suspected acute cardioembolic stroke verified by initial multimodal CT and subsequently examined with cCT were included. The cCT was evaluated for presence of major CES and compared to routine clinical echocardiographic work-up. Results In all, 102 patients with suspected acute CES underwent cCT. Among them 60 patients underwent routine work-up with echocardiography (50 TTE and only 10 TEE). By cCT 10/60 (16.7%) major CES were detected but only 4 (6.7%) were identified by echocardiography. All CES observed by echocardiography were also detected by cCT. In 8 of 36 patients in whom echocardiography was not performed cCT also revealed a major CES. Conclusion These preliminary results show the potential diagnostic yield of delayed-phase cCT to detect major CES and therefore could accelerate decision-making to prevent recurrence stroke. To confirm these results larger studies with TEE as the reference standard and also compared to TTE would be necessary.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Over the past decades, there has been tremendous progress in understanding genetic alterations that can result in different phenotypes of human cardiomyopathies. More than a thousand mutations in various genes have been identified, indicating that distinct genetic alterations, or combinations of genetic alterations, can cause either hypertrophic (HCM), dilated (DCM), restrictive (RCM), or arrhythmogenic cardiomyopathies (ARVC). Translation of these results from “bench to bedside” can potentially group affected patients according to their molecular etiology and identify subclinical individuals at high risk for developing cardiomyopathy or patients with overt phenotypes at high risk for cardiac deterioration or sudden cardiac death. These advances provide not only mechanistic insights into the earliest manifestations of cardiomyopathy, but such efforts also hold the promise that mutation-specific pathophysiology might result in novel “personalized” therapeutic possibilities. Recently, the FLNC gene encoding the sarcomeric protein filamin C has gained special interest since FLNC mutations were found in several distinct and possibly overlapping cardiomyopathy phenotypes. Specifically, mutations in FLNC were initially only linked to myofibrillar myopathy (MFM), but are now increasingly found in various forms of human cardiomyopathy. FLNC thereby represents another example for the complex genetic and phenotypic continuum of these diseases.

Recurrent stroke is considered to increase the incidence of severe disability and death. For correct risk assessment and patient management it is essential to identify the origin of stroke at an early stage. Transthoracic echocardiography (TTE) is the initial standard of care for evaluating patients in whom a cardioembolic source of stroke (CES) is suspected but its diagnostic capability is limited. Transesophageal echocardiography (TEE) is considered as gold standard; however, this approach is time consuming, semi-invasive and not always feasible. We hypothesized that adding a delayed-phase cardiac computed tomography (cCT) to initial multimodal CT might represent a valid alternative to routine clinical echocardiographic work-up. Patients with suspected acute cardioembolic stroke verified by initial multimodal CT and subsequently examined with cCT were included. The cCT was evaluated for presence of major CES and compared to routine clinical echocardiographic work-up. In all, 102 patients with suspected acute CES underwent cCT. Among them 60 patients underwent routine work-up with echocardiography (50 TTE and only 10 TEE). By cCT 10/60 (16.7%) major CES were detected but only 4 (6.7%) were identified by echocardiography. All CES observed by echocardiography were also detected by cCT. In 8 of 36 patients in whom echocardiography was not performed cCT also revealed a major CES. These preliminary results show the potential diagnostic yield of delayed-phase cCT to detect major CES and therefore could accelerate decision-making to prevent recurrence stroke. To confirm these results larger studies with TEE as the reference standard and also compared to TTE would be necessary.

Heart failure is one of the major causes of death worldwide. Its pathophysiology is complex and involves alterations in calcium cycling and hypertrophic signaling, as well as subsequent loss of cardiomyocytes due to apoptosis, cardiac fibrosis and progressive contractile dysfunction. The Striatin-interacting phosphatase and kinase (STRIPAK) complex is a mammalian multiprotein complex that consists of phosphatases, kinases and various adaptor proteins. Yet, the STRIPAK complex has so far not been studied in cardiomyocytes. Now we show in cardiomyocytes that the STRIPAK associated kinase MST4 directly interacts with a recently described novel cardiac STRIPAK protein, Myoscape/STRIP2. Multi tissue immunoblot experiments showed that Mst4 abundance is also highly enriched in heart and skeletal muscle. Immunoblot analyses in human biopsy samples form patients with dilated (DCM n=10) or ischemic cardiomyopathy (ICM n=10) revealed that MST4 is strongly upregulated in DCM (12-fold pin vitro by 30% (pin vivo (-45%, n=6; P

This work focuses on implementing a standardized and symptom-oriented flowchart for advanced cardiac imaging in a 24/7 emergency setting using a dual-layer spectral detector CT system. This flowchart was designed to optimize patient management and standardize imaging workflow. It includes acquisition parameters and contrast agent protocols for the most relevant clinical questions regarding cardiac CT imaging in the interdisciplinary emergency department. The automated reconstruction of symptom-oriented spectral images represents an additional strength here. This implementation is designed to be time-efficient and user-friendly and improves diagnostic quality, independent of the qualification level of clinical and technical personnel.

BACKGROUND The MitraClip procedure requires transseptal access of the left atrium with a 24F guiding sheath. We evaluated invasively whether a MitraClip induced iatrogenic atrial septal defect (IASD) leads to development of a relevant interatrial shunt and right ventricular overload. METHODS A total of 69 patients who underwent a MitraClip procedure due to a severe mitral valve regurgitation (MVR) were included in the observational, retrospective cohort study. All pressures were directly measured throughout the procedure. Cardiac index (CI), systemic (Qs) and pulmonary (Qp) flow were calculated using the Fick method. RESULTS Successful MitraClip implantation increased CI (2.5 ± 0.62 vs 3.05 ± 0.77 L/min/m2 ; P

Biomarkers may significantly improve risk stratification algorithms for patients undergoing transcatheter aortic valve implantation (TAVI). While N-terminal pro-B-type natriuretic peptide (NT-proBNP) is established as a biomarker in the context of heart failure, its prognostic implications in patients with normal left ventricular ejection fraction (LVEF) undergoing TAVI are unclear.A total of 504 TAVI patients with normal LVEF were analyzed. Based on preprocedural NT-proBNP levels, patients were stratified into two groups comparing the upper quartile ("Q4", n = 126) with the lower three quartiles ("Q1-3", n = 378). The primary outcome of our study was survival.The "Q4" group included more men (46.8% vs. 34.9%, p = 0.017), had higher rates of atrial fibrillation (55.6% vs. 28.3%, p 0.001) and showed features of more advanced aortic stenosis (mean pressure gradient 49 mmHg vs. 40 mmHg, aortic valve area 0.6 cmNT-proBNP is associated with survival in TAVI patients with normal LVEF. In this patient group, preprocedural NT-proBNP levels do not only correlate with aortic stenosis, but reflect advanced cardiovascular dysfunction, including HFpEF, that might not be completely reversible after TAVI.

The implications of prosthesis-patient mismatch (PPM) in the context of transcatheter aortic valve implantation (TAVI) are still controversial. The objective of our study was thus to investigate the incidence and prognostic impact of PPM after TAVI.Our analysis included 613 TAVI patients in whom the indexed effective orifice area (iEOA) after TAVI was obtained in vivo using echocardiography. Prosthesis sizing was guided by pre-procedural ECG-gated computed tomography. Based on VARC-2 established criteria for significant PPM (iEOA ≤ 0.85 cmWe observed PPM after TAVI in 192 patients (31.3%) with moderate PPM being present in 150 subjects (24.5%) and severe PPM in 42 patients (6.9%). EuroSCORE, impaired LV function, and male gender were associated with PPM status. The "No PPM" group was characterized by higher rates of self-expandable valves (40.4% vs. 25.5%, p 0.001). In a multivariate analysis age 81.2 years, chronic obstructive pulmonary disease, peripheral artery disease, impaired LV function, acute kidney failure stage 3 as well as periprocedural myocardial infarction emerged as independent risk predictors for all-cause mortality after TAVI. After a median follow-up of 12.2 months PPM failed to show a significant association with overall survival (79.2% vs. 79.3%, p = 0.692).The incidence of PPM after TAVI seems to be substantially lower than after SAVR. PPM was less common using self-expandable valves. In our analysis, patients with PPM following TAVI did not have higher rates of all-cause mortality.

INTRODUCTION With subgroups of patients with hypertrophic cardiomyopathy (HCM) confers a 4% to 5% risk for adverse prognosis. Besides left-ventricular muscle mass (LV-MM) myocardial fibrosis (MF) assessable by late gadolinium enhancement in cardiovascular magnetic resonance (LGE-CMR) has been related to that. Myocardial fibrosis can also be demonstrated by late enhancement (LE) in late-enhanced multislice computed tomography (leMDCT). This analysis investigates leMDCT whether to enable quantification of LE load in terms of LE mass by percent LV-MM in HCM. METHODS In a prospective validation study, we included 30 consecutive patients with HCM who underwent leMDCT (64 slice) and LGE-CMR (1.5 T). The leMDCT scan was performed 7 minutes after injection of iodine contrast (Iopromid). Endocardial and epicardial planimetry served for the assessment of LV-MM. Visually detectable LE was quantified using the manual quantification method resulting in LE by percent LV-MM (%LE). The LGE-CMR data served for validation. RESULTS Mean (SD) age was 64.1 (13.9) years. Myocardial fibrosis prevalence was 63.3% (19/30 patients indentified by both leMDCT and LGE-CMR). In leMDCT, tissue density in LE areas compared with normal myocardium was higher (138.2 [23.9] HU vs 98.4 [16.5] HU, P < 0.001) but lower than in the LV cavity (138.2 [23.9] HU vs 169.2 [35.9] HU, P < 0.001). Late enhancement mass in leMDCT seemed to be 7.9 (8.5) g LE versus 8.6 [11] g LGE in CMR (P = 0.497, r = 0.95) resulting in a leMDCT/LGE-CMR relation of 1.2. Referring LE mass to LV-MM gave an LE proportion measured by leMDCT of 4 (3.9) %LE versus 3.9 (4.1) %LGE in LGE-CMR (r = 0.88, P = 0.75). Intraobserver/interobserver reliability of LE mass assessment showed an intraclass correlation coefficient of 0.99 and 0.97. CONCLUSIONS In patients with HCM, leMDCT provides volumetric assessment of LE mass-absolutely and by percent LV-MM.

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Patients (pts) with hypertrophic cardiomyopathy (HCM) may present with a variety of symptoms, including sudden cardiac death. Sudden cardiac death due to ventricular fibrillation correlates with the extent of intramural fibrosis (IF). IF can be detected using cardiac magnetic resonance (CMR) by

Data from the Women’s Health Study show that serum levels of growth-differentiation factor-15 (GDF-15), a distant member of the transforming growth factor-β superfamily, are an independent risk indicator for adverse cardiovascular events. However, the cellular sources, upstream regulators, and functional effects of GDF-15 in the cardiovascular system have not been elucidated. We have identified GDF-15 by cDNA expression array analysis as a gene that is strongly upregulated by nitrosative stress in cultured cardiomyocytes isolated from 1- to 3-day-old rats. GDF-15 mRNA and pro-peptide expression levels were also induced in cardiomyocytes subjected to simulated ischemia/reperfusion (I/R) via NO–peroxynitrite-dependent signaling pathways. GDF-15 was actively secreted into the culture supernatant, suggesting that it might exert autocrine/paracrine effects during I/R. To explore the in vivo relevance of these findings, mice were subjected to transient or permanent coronary artery ligation. Myocardial GDF-15 mRNA and pro-peptide abundance rapidly increased in the area-at-risk after ischemic injury. Similarly, patients with an acute myocardial infarction had enhanced myocardial GDF-15 pro-peptide expression levels. As shown by immunohistochemistry, cardiomyocytes in the ischemic area contributed significantly to the induction of GDF-15 in the infarcted human heart. To delineate the function of GDF-15 during I/R, Gdf-15 gene-targeted mice were subjected to transient coronary artery ligation for 1 hour followed by reperfusion for 24 hours. Gdf-15 –deficient mice developed greater infarct sizes and displayed more cardiomyocyte apoptosis in the infarct border zone after I/R compared with wild-type littermates, indicating that endogenous GDF-15 limits myocardial tissue damage in vivo. Moreover, treatment with recombinant GDF-15 protected cultured cardiomyocytes from apoptosis during simulated I/R as shown by histone ELISA, TUNEL/Hoechst staining, and annexin V/propidium iodide fluorescence-activated cell sorting (FACS) analysis. Mechanistically, the prosurvival effects of GDF-15 in cultured cardiomyocytes were abolished by phosphoinositide 3-OH kinase inhibitors and adenoviral expression of dominant-negative Akt1 (K179M mutation). In conclusion, our study identifies induction of GDF-15 in the heart as a novel defense mechanism that protects from I/R injury.