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Background: Aortic stenosis (AS) is one of the most prevalent valvular heart-diseases in Europe. Currently, diagnosis and classification are not sex-sensitive; however, due to a distinctly different natural history of AS, further investigations of sex-differences in AS-patients are needed. Thus, this study aimed to detect sex-differences in severe AS, especially concerning flow-patterns, via phase-contrast cardiac magnetic resonance imaging (PC-CMR)., Methods: Forty-four severe AS-patients (20 women, 45 % vs. 24 men, 55 %) with a median age of 72 years underwent transthoracic echocardiography (TTE), cardiac catheterization (CC) and CMR. Aortic valve area (AVA) and stroke volume (SV) were determined in all modalities, with CMR yielding geometrical AVA via cine-planimetry and functional AVA via PC-CMR, the latter being also used to examine flow-properties., Results: Geometrical AVA showed no sex-differences (0.91 cm 2 , IQR: 0.61-1.14 vs. 0.94 cm 2 , IQR: 0.77-1.22, p = 0.322). However, functional AVA differed significantly between sexes in all three modalities (TTE: p = 0.044; CC/PC-CMR: p < 0.001). In men, no significant intermethodical biases in functional AVA-measurements between modalities were found (p = 0.278); yet, in women the particular measurements differed significantly (p < 0.001). Momentary flowrate showed sex-differences depending on momentary opening-degree (at 50 %, 75 % and 90 % of peak-AVA, all p < 0.001), with men showing higher flowrates with increasing opening-area. In women, flowrate did not differ between 75 % and 90 % of peak-AVA (p = 0.191)., Conclusions: In severe AS-patients, functional AVA showed marked sex-differences in all modalities, whilst geometrical AVA did not differ. Inter-methodical biases were negligible in men, but not in women. Lastly, significant sex-differences in flow-patterns fit in with the different pathogenesis of AS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

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., Competing Interests: Disclosures None.

Background: Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function., Methods: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life., Discussion: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure., Trial Registration: ClinicalTrials.gov NCT03859466. Registered on 1 March 2019., (© 2022. The Author(s).)

Background: Mitral annular disjunction (MAD) represents the detachment of the mitral leaflet hinge-point from the ventricular myocardium. Its role in patients with ST-segment-elevation myocardial infarction (STEMI) is unknown. This study aims to investigate the prevalence of MAD by cardiac magnetic resonance imaging (CMR) in STEMI-patients and its association with serious adverse events., Methods: STEMI-patients (n = 621) underwent CMR 4 days [interquartile range (IQR) 2-5] after percutaneous coronary intervention. Presence and longitudinal extent of MAD were obtained in long-axis cine-images, infarct characteristics in late gadolinium enhancement-images. During a median follow-up time of 366 days (IQR 136-454), patients were observed for the occurrence of major adverse cardiac events (MACE), comprising death, myocardial reinfarction, and congestive heart failure., Results: Overall, 307 patients (49 %) had MAD. Longitudinal MAD-distance was 4.6 ± 1.7 mm and the P3-segment was affected most frequently (n = 262, 85 % of MAD-patients). MAD-patients had a significantly smaller infarct size, lower prevalence of microvascular obstruction, and intramyocardial hemorrhage as well as a higher ejection fraction (all p < 0.03). During follow-up period, MACE occurred in 52 patients (8 %) and did not show significant difference between patients with and without MAD (7 % vs. 9 %, p = 0.424). Cardiovascular death occurred significantly more often in patients without MAD (n = 10, 3.2 % vs. n = 2, 0.7 %, p = 0.021)., Conclusion: MAD is a rather common finding in patients presenting with STEMI. Patients with MAD had less severe infarct characteristics, however, they were not more commonly affected by MACE. Further confirmation and longer follow-up intervals are necessary to define the exact role of MAD in STEMI patients., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The standard procedure for the planning of transcatheter aortic valve replacement (TAVR) is the combination of echocardiography, coronary angiography, and cardiovascular computed tomography (TAVR-CT) for the exact determination of the aortic valve dimensions, valve size, and implantation route. However, up to 80% of the patients undergoing TAVR suffer from chronic renal insufficiency. Alternatives to reduce the need for iodinated contrast agents are desirable. Cardiac magnetic resonance (CMR) imaging recently has emerged as such an alternative. Therefore, we aim to investigate, for the first time, the non-inferiority of TAVR-CMR to TAVR-CT regarding efficacy and safety end-points., Methods: This is a prospective, randomized, open-label trial. It is planned to include 250 patients with symptomatic severe aortic stenosis scheduled for TAVR based on a local heart-team decision. Patients will be randomized in a 1:1 fashion to receive a predefined TAVR-CMR protocol or to receive a standard TAVR-CT protocol within 2 weeks after inclusion. Follow-up will be performed at hospital discharge after TAVR and after 1 and 2 years. The primary efficacy outcome is device implantation success at discharge. The secondary endpoints are a combined safety endpoint and a combined clinical efficacy endpoint at baseline and at 1 and 2 years, as well as a comparison of imaging procedure related variables. Endpoint definitions are based on the updated 2012 VARC-2 consensus document., Discussion: TAVR-CMR might be an alternative to TAVR-CT for planning a TAVR procedure. If proven to be effective and safe, a broader application of TAVR-CMR might reduce the incidence of acute kidney injury after TAVR and thus improve outcomes., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT03831087). The results will be disseminated at scientific meetings and publication in peer-reviewed journals., (© 2022. The Author(s).)

Background: In patients with a first ST-segment elevation myocardial infarction (STEMI), the multi-annual evolution of myocardial tissue injury parameters, as assessed by cardiac magnetic resonance (CMR), has not yet been described., Objectives: This study examined myocardial tissue injury dynamics over a decade after STEMI., Methods: Sequential CMR examinations (within the first week after STEMI, and at 4, 12, months, and 9 years thereafter) were conducted in 74 patients with STEMI treated with primary percutaneous coronary intervention. Left ventricular function, infarct size (IS), and microvascular obstruction (MVO) were assessed at all time points. T2∗, T2, and T1 mapping (n = 59) were added at 9-year scan to evaluate the presence of iron and edema within the infarct core, respectively., Results: IS decreased progressively and significantly between all CMR time points (all P < 0.001), with an average reduction rate of 5.8% per year (IQR: 3.5%-8.8%) and a relative reduction of 49% (IQR: 39%-76%) over a decade. MVO was present in 61% of patients at baseline, but was not present at the follow-up examinations. At 9-year CMR, 17 of 59 (29%) patients showed iron deposition within the infarct core, whereas 82% had persistent edema. Persistent iron and edema were associated with greater IS on any occasion (all P < 0.001), as well as the presence of MVO (P < 0.001). Patients with persistent iron and edema showed a lower relative regression of IS (P = 0.005 and P = 0.032, respectively) and greater end-systolic volumes over a decade (all P < 0.012 and P > 0.023, respectively). A T1 hypointense infarct core without evidence of T2∗ iron deposition (14 of 59 [24%] patients) was attributed to lipomatous metaplasia of the infarct., Conclusions: The evolution of IS is a dynamic process that extends well beyond the first few months after STEMI. Persistence of iron and edema within the infarct core occurs up to a decade after STEMI and is associated with initial infarct severity and poor infarct healing., Competing Interests: Funding Support and Author Disclosures The study was supported by grants from the Austrian Science Fund (FWF): KLI 772-B (BM) and by the Austrian Society of Cardiology. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Transthoracic echocardiography (TTE) is the diagnostic routine standard for assessing aortic stenosis (AS). However, its inaccuracies in determining stroke volume (SV) and aortic valve area (AVA) call for a more precise and dependable method. Phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) is a promising tool to push these boundaries. Thus, the aim of this study was to validate a novel approach based on PC-CMR against the gold-standard of invasive determination of AVA in AS compared to TTE., Methods: A total of 50 patients with moderate or severe AS underwent TTE, cardiac catheterization and CMR. AVA via PC-CMR was determined by plotting momentary flow across the valve against flow-velocity. SV by CMR was measured directly via PC-CMR and volumetrically using cine-images. Invasive SV and AVA were determined via Fick-principle and Gorlin-formula, respectively. TTE yielded SV and AVA using continuity equation. Gradients were calculated via the modified Bernoulli-equation., Results: SV by PC-CMR (85 ± 31 ml) correlated strongly (r: 0.73, p < 0.001) with cine-CMR (85 ± 19 ml) without significant bias (lower and upper limits of agreement (LLoA and ULoA): - 41 ml and 44 ml, p = 0.83). In PC-CMR, mean pressure gradient correlated significantly with invasive determination (r: 0.36, p = 0.011). Mean AVA, as determined by PC-CMR during systole (0.78 ± 0.25 cm 2 ), correlated moderately (r: 0.54, p < 0.001) with invasive AVA (0.70 ± 0.23 cm 2 ), resulting in a small bias of 0.08 cm 2 (LLoA and ULoA: - 0.36 cm 2 and 0.55 cm 2 , p = 0.017). Inter-methodically, AVA by TTE (0.81 ± 0.23 cm 2 ) compared to invasive determination showed similar correlations (r: 0.58, p < 0.001 with a bias of 0.11 cm 2 , LLoA and ULoA: - 0.30 and 0.52, p < 0.001) to PC-CMR. Intra- and interobserver reproducibility were excellent for AVA (intraclass-correlation-coefficients of 0.939 and 0.827, respectively)., Conclusions: Our novel approach using continuous determination of flow-volumes and velocities with PC-CMR enables simple AVA measurement with no bias to invasive assessment. This approach highlights non-invasive AS grading through CMR, especially when TTE findings are inconclusive., (© 2021. The Author(s).)

Background: Coronary artery diseases (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodeling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave Therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function., Methods/design: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min Walk Test distance, improvement of symptoms and assessment of quality of life., Discussion: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure., Trial Registration: ClinicalTrials.gov, ID: NCT03859466. Registered on 1 March 2019.

Background In survivors of acute ST-segment-elevation myocardial infarction (STEMI), increased aortic stiffness is associated with worse clinical outcome; however, the underlying pathomechanisms are incompletely understood. We aimed to investigate associations between aortic stiffness and infarct healing using comprehensive cardiac magnetic resonance imaging in patients with acute STEMI. Methods and Results This was a prospective observational study including 103 consecutive STEMI patients treated with primary percutaneous coronary intervention. Pulse wave velocity (PWV), the reference standard for aortic stiffness assessment, was determined by a validated phase-contrast cardiac magnetic resonance imaging protocol within the first week after STEMI. Infarct healing, defined as relative infarct size reduction from baseline to 4 months post-STEMI, was determined using late gadolinium-enhanced cardiac magnetic resonance. Median infarct size significantly decreased from 17% of left ventricular mass (interquartile range 9% to 28%) at baseline to 12% (6% to 17%) at 4-month follow-up ( P <0.001). Relative infarct size reduction was 36% (interquartile range 15% to 52%). Patients with a reduction >36% were younger ( P =0.01) and had lower baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentrations ( P =0.047) and aortic PWV values ( P =0.003). In a continuous (odds ratio 0.64 [95% CI, 0.49-0.84]; P =0.001) as well as categorical (PWV <7 m/s; odds ratio 4.80 [95% CI, 1.89-12.20]; P =0.001) multivariable logistic regression model, the relation between aortic PWV and relative infarct size reduction remained significant after adjustment for baseline infarct size, age, NT-proBNP, and C-reactive protein. Conclusions Aortic PWV independently predicted infarct size reduction as assessed by cardiac magnetic resonance, revealing a novel pathophysiological link between aortic stiffness and adverse infarct healing during the early phase after STEMI treated with contemporary primary percutaneous coronary intervention.

Background: The high accuracy of feature-tracking cardiac magnetic resonance (CMR) imaging qualifies this novel modality as potential gold standard for myocardial strain analyses in ST-elevation myocardial infarction patients; however, the incremental prognostic validity of feature-tracking-CMR over left ventricular ejection fraction (LVEF) and myocardial damage remains unclear. This study therefore aimed to determine the value of myocardial strain measured by feature-tracking-CMR for the prediction of clinical outcome following ST-elevation myocardial infarction., Methods: This prospective observational study enrolled 451 revascularized ST-elevation myocardial infarction patients. Comprehensive CMR investigations were performed 3 (interquartile range, 2-4) days after infarction to determine LVEF, global longitudinal strain (GLS), global radial strain, and global circumferential strain as well as myocardial damage. Primary end point was a composite of death, re-infarction, and congestive heart failure (major adverse cardiac events [MACE])., Results: During a follow-up of 24 (interquartile range, 11-48) months, 46 patients (10%) experienced a MACE event. All 3 strain indices were impaired in patients with MACE (all P <0.001). However, GLS emerged as the strongest MACE prognosticator among strain parameters (area under the curve, 0.73 [95% CI, 0.69-0.77]) and was significantly better ( P =0.005) than LVEF (area under the curve, 0.64 [95% CI, 0.59-0.68]). The association between GLS and MACE remained significant ( P <0.001) after adjustment for global radial strain, global circumferential strain, and LVEF as well as for infarct size and microvascular obstruction. The addition of GLS to a risk model comprising LVEF, infarct size, and microvascular obstruction led to a net reclassification improvement (0.35 [95% CI, 0.14-0.55]; P <0.001)., Conclusions: GLS by feature-tracking-CMR strongly and independently predicted the occurrence of medium-term MACE in contemporary revascularized ST-elevation myocardial infarction patients. Importantly, the prognostic value of GLS was superior and incremental to LVEF and CMR markers of infarct severity.

Background Acute complete occlusion of a coronary artery results in progressive ischemia, moving from the endocardium to the epicardium (ie, wavefront). Dependent on time to reperfusion and collateral flow, myocardial infarction ( MI ) will manifest, with transmural MI portending poor prognosis. Late gadolinium enhancement cardiac magnetic resonance imaging can detect MI with  high diagnostic accuracy. Primary percutaneous coronary intervention is the preferred reperfusion strategy in patients with ST -segment-elevation MI with <12 hours of symptom onset. We sought to visualize time-dependent necrosis in a population with ST -segment-elevation MI by using late gadolinium enhancement cardiac magnetic resonance imaging (STEMI-SCAR project). Methods and Results ST -segment-elevation MI patients with single-vessel disease, complete occlusion with TIMI (Thrombolysis in Myocardial Infarction) score 0, absence of collateral flow (Rentrop score 0), and symptom onset <12 hours were consecutively enrolled. Using late gadolinium enhancement cardiac magnetic resonance imaging, the area at risk and infarct size, myocardial salvage index, transmurality index, and transmurality grade (0-50%, 51-75%, 76-100%) were determined. In total, 164 patients (aged 54±11 years, 80% male) were included. A receiver operating characteristic curve (area under the curve: 0.81) indicating transmural necrosis revealed the best diagnostic cutoff for a symptom-to-balloon time of 121 minutes: patients with >121 minutes demonstrated increased infarct size, transmurality index, and transmurality grade (all P<0.01) and decreased myocardial salvage index ( P<0.001) versus patients with symptom-to-balloon times ≤121 minutes. Conclusions In MI with no residual antegrade and no collateral flow, immediate reperfusion is vital. A symptom-to-balloon time of >121 minutes causes a high grade of transmural necrosis. In this pure ST -segment-elevation MI population, time to reperfusion to salvage myocardium was less than suggested by current guidelines.