Mst4, a novel cardiac STRIPAK complex-associated kinase, regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy.

Myocardial failure is associated with adverse remodeling, including loss of cardiomyocytes, hypertrophy, and alterations in cell-cell contacts. Striatin-interacting phosphatase and kinase (STRIPAK) complexes and their mammalian STE20-like kinase 4 (Mst4) have been linked to development of different diseases. The role and targets of Mst4 in cardiomyocytes have not been investigated yet. Multitissue immunoblot experiments show highly enriched Mst4 expression in rodent hearts. Analyses of human biopsy samples from patients suffering from dilated cardiomyopathy revealed that Mst4 is upregulated (5- to 8-fold p < 0.001) compared with nonfailing controls. Increased abundance of Mst4 could also be detected in mouse models of cardiomyopathy. We confirmed that Mst4 interacts with STRIPAK components in neonatal rat ventricular cardiomyocytes, indicating that STRIPAK is present in the heart. Immunofluorescence stainings and molecular interaction studies revealed that Mst4 is localized to the intercalated disc and interacts with several intercalated disc proteins. Overexpression of Mst4 in cardiomyocytes results in hypertrophy compared with controls. In adult rat cardiomyocytes, Mst4 overexpression increases cellular and sarcomeric fractional shortening (p < 0.05), indicating enhanced contractility. Overexpression of Mst4 also inhibits apoptosis shown by reduction of cleaved caspase3 (-69%, p < 0.0001), caspase7 (-80%, p < 0.0001), and cleaved Parp1 (-27%, p < 0.001). To elucidate potential Mst4 targets, we performed phosphoproteomics analyses in neonatal rat cardiomyocytes after Mst4 overexpression and inhibition. The results revealed target candidates of Mst4 at the intercalated disc. We identified Mst4 as a novel cardiac kinase that is upregulated in cardiomyopathy-regulating cardiomyocyte growth and survival.

An ex-vivo and in-vitro dynamic simulator for surgical and transcatheter mitral valve interventions.

PURPOSE: Minimally invasive mitral valve surgery (MIMVS) and transcatheter edge-to-edge repair (TEER) are complex procedures used to treat mitral valve (MV) pathologies, but with limited training opportunities available. To enable training, a realistic hemodynamic environment is needed. In this work we aimed to develop and validate a simulator that enables investigation of MV pathologies and their repair by MIMVS and TEER in a hemodynamic setting. METHODS: Different MVs were installed in the simulator, and pressure, flow, and transesophageal echocardiographic measurements were obtained. To confirm the simulator's physiological range, we first installed a biological prosthetic, a mechanical prosthetic, and a competent excised porcine MV. Subsequently, we inserted two porcine MVs-one with induced chordae tendineae rupture and the other with a dilated annulus, along with a patient-specific silicone valve extracted from echocardiography with bi-leaflet prolapse. Finally, TEER and MIMVS procedures were conducted by experts to repair the MVs. RESULTS: Systolic pressures, cardiac outputs, and regurgitations volumes (RVol) with competent MVs were 119 ± 1 mmHg, 4.78 ± 0.16 l min-1, and 5 ± 3 ml respectively, and thus within the physiological range. In contrast, the pathological MVs displayed increased RVols. MIMVS and TEER resulted in a decrease in RVols and mitigated the severity of mitral regurgitation. CONCLUSION: Ex-vivo modelling of MV pathologies and repair procedures using the described simulator realistically replicated physiological in-vivo conditions. Furthermore, we showed the feasibility of performing MIMVS and TEER at the simulator, also at patient-specific level, thus providing new clinical perspectives in terms of training modalities and personalized planning.

Complications in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy: distribution and relevance. Results from an international, multicentre cohort study.

AIMS: Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). METHODS AND RESULTS: All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005-2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 patients (58%). Thirty-days mortality was 40% (198/501 patients). At least one device-related complication occurred in 252/486 (52%) patients, neurological AEs in 108/469 (23%), bleeding in 192/480 (40%), ischaemic AEs in 123/478 (26%). The 22% of patients with the most AEs accounted for 50% of all AEs. All types of AEs were associated with a worse prognosis. Aside from neurological ones, all AEs and device-related complications were more likely to occur in women; although prediction of AEs outside of neurological AEs was generally poor. CONCLUSION: Therapy and device-related complications occur in half of all patients treated with VA-ECMO and are associated with a worse prognosis. They accumulate in some patients, especially in women. Aside from neurological events, identification of patients at risk is difficult, highlighting the need to establish additional quantitative markers of complication risk to guide VA-ECMO treatment in CS.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Subannular repair in secondary mitral regurgitation with restricted leaflet motion during systole.

OBJECTIVE: Ventricular secondary mitral regurgitation (SMR) (Carpentier type IIIb) results from left ventricular (LV) remodelling, displacement of papillary muscles and tethering of mitral leaflets. The most appropriate treatment approach remains controversial. We aimed to assess the safety and efficacy of standardised relocation of both papillary muscles (subannular repair) at 1-year follow-up (FU). METHODS: REFORM-MR (Reform-Mitral Regurgitation) is a prospective, multicentre registry that enrolled consecutive patients with ventricular SMR (Carpentier type IIIb) undergoing standardised subannular mitral valve (MV) repair in combination with annuloplasty at five sites in Germany. Here, we report survival, freedom from recurrence of MR >2+, freedom from major adverse cardiac and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, MV reintervention and echocardiographic parameters of residual leaflet tethering at 1-year FU. RESULTS: A total of 94 patients (69.1% male) with a mean age of 65.1±9.7 years met the inclusion criteria. Advanced LV dysfunction (mean left ventricular ejection fraction 36.4±10.5%) and severe LV dilatation (mean left ventricular end-diastolic diameter 61.0±9.3 mm) resulted in severe mitral leaflet tethering (mean tenting height 10.6±3.0 mm) and an elevated mean EURO Score II of 4.8±4.6 prior to surgery. Subannular repair was successfully performed in all patients, without operative mortality or complications. One-year survival was 95.5%. At 12 months, a durable reduction of mitral leaflet tethering resulted in a low rate (4.2%) of recurrent MR >2+. In addition to a significant improvement in New York Heart Association (NYHA) class (22.4% patients in NYHA III/IV vs 64.5% patients at baseline, p<0.001), freedom from MACCE was observed in 91.1% of patients. CONCLUSIONS: Our study demonstrates the safety and feasibility of standardised subannular repair to treat ventricular SMR (Carpentier type IIIb) in a multicentre setting. By addressing mitral leaflet tethering, papillary muscle relocation results in very satisfactory 1-year outcomes and has the potential to durably restore MV geometry; nevertheless, long-term FU is mandatory. TRIAL REGISTRATION NUMBER: NCT03470155.

Timing of Active Left Ventricular Unloading in Patients on Venoarterial Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND: It is currently unclear if active left ventricular (LV) unloading should be used as a primary treatment strategy or as a bailout in patients with cardiogenic shock (CS) treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). OBJECTIVES: This study sought to evaluate the association between timing of active LV unloading and implantation of VA-ECMO with outcomes of patients with CS. METHODS: Data from 421 patients with CS treated with VA-ECMO and active LV unloading at 18 tertiary care centers in 4 countries were analyzed. Patients were stratified by timing of device implantation in early vs delayed active LV unloading (defined by implantation before up to 2 hours after VA-ECMO). Adjusted Cox and logistic regression models were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as successful weaning from ventilation. RESULTS: Overall, 310 (73.6%) patients with CS were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (HR: 0.64; 95% CI: 0.46-0.88) and a higher likelihood of successful weaning from ventilation (OR: 2.17; 95% CI: 1.19-3.93) but not with more complications. Importantly, the relative mortality risk increased and the likelihood of successful weaning from ventilation decreased almost proportionally with the time interval between VA-ECMO implantation and (delayed) initiation of active LV unloading. CONCLUSIONS: This exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO, although the findings need to be validated in a randomized controlled trial.

A practical approach to the guideline-directed pharmacological treatment of heart failure with reduced ejection fraction.

Over the last 15-20 years, remarkable developments of heart failure (HF) pharmacotherapies have been achieved. However, HF remains a global healthcare challenge with more than 64 million patients worldwide. Optimization of guideline-directed chronic HF medical therapy is highly recommended with every patient visit to improve outcomes in patients with HF with reduced ejection fraction. However, the majority of patients in real-world settings are treated with doses that are lower than those with proven efficacy in clinical trials, which might be due to concerns of adverse effects and inertia of physicians. Likewise, a significant proportion of patients still do not receive all drug classes that could improve their prognosis. The recent European Society of Cardiology guidelines do not provide detailed recommendations on how these drug classes should be implemented in the treatment of inpatients to allow for both safety and a high likelihood of efficacy. We therefore propose a practical approach algorithm to support physicians to treat HF patients in their daily practice.

Subannular repair for functional mitral regurgitation with reduced systolic ventricle function: rationale and design of REFORM-MR registry.

BACKGROUND: Functional mitral regurgitation (FMR) is one of the most common heart valve diseases that is a sequel of left ventricular remodelling. Although mitral valve annuloplasty is a standard treatment of FMR, the recurrence of FMR is a major drawback and occurs in 10-50% of patients. The REFORM-MR registry aims to investigate the effectiveness of standardized papillary muscle relocation and ring annuloplasty and to identify the risk factors associated with recurrent FMR. METHODS: REFORM-MR is a prospective, multicenter registry that enrols consecutive FMR patients across five sites in Germany. All patients with FMR and restricted movement of leaflets during systole (i.e., type IIIb mitral regurgitation) undergoing standardized subannular repair in combination with mitral valve annuloplasty are included in the study. The primary objective is to examine the effect of combined papillary muscle relocation and ring annuloplasty on the recurrence of FMR at 2 years postoperatively. The secondary objectives are MACCE rate, reinterventions on the mitral valve and cardiac-related mortality in the study cohort. Echocardiography core-lab and MRI core-lab will provide anonymized analysis of the imaging data in the REFORM-MR registry. Student's t-test or Mann-Whitney U test for continuous variables and the Chi-Square or Fisher exact test for categorical variables are used for group comparisons. Kaplan-Meier analyses is performed for survival and safety outcomes. RESULTS: As of May 2021, a total of 97 patients were enrolled across five sites in Germany. CONCLUSIONS: The results of this study will help define the outcomes of combined papillary muscle relocation and ring annuloplasty in the FMR treatment in a multicentre setting and to improve the understanding of the limitations of subannular repair procedures while treating patients with type III FMR. Trial registration clinicaltrials.gov Identifier: NCT03470155.

[A practical approach to guideline-directed pharmacological treatment for heart failure with reduced ejection fraction]. / Frühe Implementierung der "Fantastic four" bei Herzinsuffizienz mit reduzierter Ejektionsfraktion.

The 2021 guidelines of the European Society of Cardiology for the diagnosis and treatment of heart failure recommend the early implementation of all four mortality-lowering drug classes for heart failure with reduced ejection fraction (HFrEF), i. e. angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor II blocker-neprilysin inhibitor (ARNI), betablocker (BB), mineralocorticoid receptor-antagonists (MRA), and sodium-glucose linked transporter-2 inhibitors (SGLT2i). This article aims to give a practical compendium supporting physicians to enable safe and efficacious treatment for patients with HFrEF.

Implementing a standardized and symptom-oriented flowchart "Kielsflow" for advanced cardiac imaging in a 24/7 interdisciplinary emergency department using spectral CT.

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.

Practicability and Diagnostic Yield of One-Stop Stroke CT with Delayed-Phase Cardiac CT in Detecting Major Cardioembolic Sources of Acute Ischemic Stroke : A Proof of Concept Study.

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.

Cardiac Filaminopathies: Illuminating the Divergent Role of Filamin C Mutations in Human Cardiomyopathy.

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.

Dysbindin deficiency Alters Cardiac BLOC-1 Complex and Myozap Levels in Mice.

Dysbindin, a schizophrenia susceptibility marker and an essential constituent of BLOC-1 (biogenesis of lysosome-related organelles complex-1), has recently been associated with cardiomyocyte hypertrophy through the activation of Myozap-RhoA-mediated SRF signaling. We employed sandy mice (Dtnbp1_KO), which completely lack Dysbindin protein because of a spontaneous deletion of introns 5-7 of the Dtnbp1 gene, for pathophysiological characterization of the heart. Unlike in vitro, the loss-of-function of Dysbindin did not attenuate cardiac hypertrophy, either in response to transverse aortic constriction stress or upon phenylephrine treatment. Interestingly, however, the levels of hypertrophy-inducing interaction partner Myozap as well as the BLOC-1 partners of Dysbindin like Muted and Pallidin were dramatically reduced in Dtnbp1_KO mouse hearts. Taken together, our data suggest that Dysbindin's role in cardiomyocyte hypertrophy is redundant in vivo, yet essential to maintain the stability of its direct interaction partners like Myozap, Pallidin and Muted.

Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study.

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.

Haemodynamics of an iatrogenic atrial septal defect after MitraClip implantation.

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 < .0001), whereas SVR (1491 ± 474 vs 997 ± 301 dyn s/cm5 ; P < .0001), PVR (226 ± 121 vs 188 ± 96 dyn/s/cm5 ; P = .04), PCWP (23 ± 6.1 vs 20 ± 4.7 mm Hg; P = .0031), PA pressure (33.6 ± 7.2 vs 31.9 ± 6.6 mm Hg; P = .1437) and LA pressure (21.5 ± 5.4 vs 18.7 ± 4.9 mm Hg; P < .0001) all decreased. The effect on LA pressure was further enhanced by guiding catheter retrieval (14.4 ± 4.6 mm Hg; P < .0001). At the end of the procedure, Qp (6.033 ± 1.3 L/min) exceeded Qs (5.537 ± 1.3 L/min) by 0.496 L/min leading to a Qp:Qs ratio of 1.09 (P = .007). After 6 months, echocardiography revealed no changes in RV diameter (42.96 ± 6.95 mm vs 43.81 ± 7.67 mm; P = .62) and TAPSE (17.13 ± 3.33 mm vs 17.36 ± 3.24 mm; P = .48). CONCLUSION: Our data show that the MitraClip procedure does not induce a relevant interatrial shunt or right ventricular overload. In fact, future studies will have to show whether the IASD may even be beneficial in selected patient populations by left atrial volume and pressure relief.

Clinical Value of Noncontrast-Enhanced Radial Quiescent-Interval Slice-Selective (QISS) Magnetic Resonance Angiography for the Diagnosis of Acute Pulmonary Embolism Compared to Contrast-Enhanced Computed Tomography and Cartesian Balanced Steady-State Free Precession.

BACKGROUND: Free-breathing noncontrast-enhanced (non-CE) magnetic resonance angiography (MRA) techniques are of considerable interest for the diagnosis of acute pulmonary embolism (APE), due to the possibility for repeated examinations, avoidance of side effects from iodine-based contrast agents, and the absence of ionizing radiation exposure as compared to CE-computed tomographic angiography (CTA). PURPOSE: To analyze the clinical performance of free-breathing and electrocardiogram (ECG)-gated radial quiescent-interval slice-selective (QISS)-MRA compared to CE-CTA and to Cartesian balanced steady-state free precession (bSSFP)-MRA. STUDY TYPE: Prospective. SUBJECTS: Thirty patients with confirmed APE and 30 healthy volunteers (HVs). FIELD STRENGTH/SEQUENCE: Radial QISS- and bSSFP-MRA at 1.5T. ASSESSMENT: Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were computed to compare the pulmonary imaging quality between MRA methods. The pulmonary arterial tree was divided into 25 branches and an ordinal scoring system was used to assess the image quality of each pulmonary branch. The clinical performance of the two MRA techniques in accurately assessing APE was evaluated with respect to CE-CTA as the clinical reference standard. STATISTICAL TESTS: Wilcoxon signed-rank and Spearman's correlation tests were performed. Sensitivity and specificity of the MRA techniques were determined using CE-CTA as the clinical reference standard. RESULTS: Thrombus-mimicking artifacts appeared more frequently in lobar and peripheral arteries of patients with Cartesian bSSFP than with radial QISS-MRA (pulmonary trunk: 12.2% vs. 14.0%, P = 0.64; lobar arteries: 35.6% vs. 22.0%, P = 0.005, peripheral arteries: 74.4% vs. 49.0%, P < 0.001). The relative increases in SNR and of CNR provided by radial QISS-MRA with respect to Cartesian bSSFP-MRA were 30-35% (P-values of SNR/CNR, HVs: 0.09/0.09, patients: 0.03/0.02). The image quality of pulmonary arterial branches was considered good to excellent in 77.2% of patients with radial QISS-MRA and in 43.2% with Cartesian bSSFP-MRA (P < 0.0001). The clinical performance of radial QISS-MRA was higher than Cartesian bSSFP-MRA for grading embolism, with a total sensitivity of 86.0% vs. 80.6% and a specificity of 93.3% vs. 84.0%, respectively. DATA CONCLUSION: Radial QISS-MRA is a reliable and safe non-CE angiographic technique with promising clinical potential compared to Cartesian bSSFP-MRA and as an alternative technique to CE-CTA for the diagnosis of APE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

Non-contrast enhanced diagnosis of acute myocarditis based on the 17-segment heart model using 2D-feature tracking magnetic resonance imaging.

PURPOSE: The aim of this study was to investigate the diagnostic value of myocardial deformation analysis based on the 17-segment heart model using non-contrast enhanced (CE) 2D tissue feature tracking (2D-FT) technique. MATERIAL AND METHODS: Seventy patients with suspected myocarditis underwent a cardiovascular magnetic resonance (CMR) examination at 1.5 Tesla. A contrast-agent-free part of this CMR protocol was additionally performed in forty healthy volunteers (HV). Besides standard CMR data sets, 2D-FT derived segmental and global longitudinal, radial, and circumferential deformation parameters were analyzed. The 2D-FT results were compared to the combined findings from CMR imaging and endomyocardial biopsy (EMB). RESULTS: Patients were assigned to three groups depending on their ejection fraction (EF) (<40%, 40-55%, ≥55%). Compared to HV, impaired EF (<55%) was significantly correlated to reduced segmental and global strain and strain rate values. The circumferential deformation analysis was more sensitive to myocardial changes than longitudinal and radial analysis. The segmental strain/strain rate had an accuracy of 84.3%/70.0% for the diagnosis of an acute myocarditis, stated by EMB and CMR in 42 of 70 patients. In patients with preserved EF, acute myocarditis could be ruled out using only segmental strain analysis with a negative predictive value of 87.5%. CONCLUSION: In patients with suspected myocarditis, the deformation analysis based on the 17-segment heart model provides valuable information about functional myocardial inhomogeneity. This quantitative approach could be used in addition to the clinical standard CMR protocol and represents a promising tool in the framework of a prospective automatized multiparametric CMR imaging analysis.

Prognostic implications of N-terminal pro-B-type natriuretic peptide in patients with normal left ventricular ejection fraction undergoing transcatheter aortic valve implantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 cm2 vs. 0.7 cm2; p < 0.001, respectively). The "Q4" group was also characterized by more extensive cardiac remodeling including severe diastolic dysfunction (18.1% vs. 6.5%, p < 0.001) and left atrial dilation (26.8% vs. 10.8%, p < 0.001). Kaplan-Meier analysis demonstrated superior survival of the "Q1-3" group (median follow-up 22.1 months, log-rank test p < 0.001). In a multivariable analysis, preprocedural NT-proBNP emerged as a significant risk factor for all-cause mortality after TAVI (HR 1.87, CI 1.31-2.65, p < 0.001). CONCLUSIONS: NT-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.

Incidence and impact of prosthesis-patient mismatch following transcatheter aortic valve implantation.

INTRODUCTION: 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. METHODS: 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 cm2/m2 in the setting of BMI < 30 kg/m2 and iEOA ≤ 0.7 cm2/m2 in the context of BMI ≥ 30 kg/m2), patients were attributed to a "No PPM" or a "PPM" group. RESULTS: We 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). CONCLUSIONS: 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.