Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial.

BACKGROUND AND AIMS: In chronic ischaemic heart failure, revascularisation strategies control symptoms but are less effective in improving left ventricular ejection fraction (LVEF). The aim of this trial is to investigate the safety of cardiac shockwave therapy (SWT) as a novel treatment option and its efficacy in increasing cardiac function by inducing angiogenesis and regeneration in hibernating myocardium. METHODS: In this single-blind, parallel-group, sham-controlled trial (cardiac shockwave therapy for ischemic heart failure, CAST-HF; NCT03859466) patients with LVEF ≤40% requiring surgical revascularisation were enrolled. Patients were randomly assigned to undergo direct cardiac SWT or sham treatment in addition to coronary bypass surgery. The primary efficacy endpoint was the improvement in LVEF measured by cardiac magnetic resonance imaging from baseline to 360 days. RESULTS: Overall, 63 patients were randomized, out of which 30 patients of the SWT group and 28 patients of the Sham group attained 1-year follow-up of the primary endpoint. Greater improvement in LVEF was observed in the SWT group (Δ from baseline to 360 days: SWT 11.3%, SD 8.8; Sham 6.3%, SD 7.4, P = .0146). Secondary endpoints included the 6-minute walking test, where patients randomized in the SWT group showed a greater Δ from baseline to 360 days (127.5 m, SD 110.6) than patients in the Sham group (43.6 m, SD 172.1) (P = .028) and Minnesota Living with Heart Failure Questionnaire score on day 360, which was 11.0 points (SD 19.1) for the SWT group and 17.3 points (SD 15.1) for the Sham group (P = .15). Two patients in the treatment group died for non-device-related reasons. CONCLUSIONS: In conclusion, the CAST-HF trial indicates that direct cardiac SWT, in addition to coronary bypass surgery improves LVEF and physical capacity in patients with ischaemic heart failure.

Mitral annular disjunction in out-of-hospital cardiac arrest patients-a retrospective cardiac MRI study.

BACKGROUND: Mitral annular disjunction (MAD), defined as defective attachment of the mitral annulus to the ventricular myocardium, has recently been linked to malignant arrhythmias. However, its role and prognostic significance in patients requiring cardiopulmonary resuscitation (CPR) remain unknown. This retrospective analysis aimed to describe the prevalence and significance of MAD by cardiac magnetic resonance (CMR) imaging in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Eighty-six patients with OHCA and a CMR scan 5 days after CPR (interquartile range (IQR): 49 days before - 9 days after) were included. MAD was defined as disjunction-extent ≥ 1 mm in CMR long-axis cine-images. Medical records were screened for laboratory parameters, comorbidities, and a history of arrhythmia. RESULTS: In 34 patients (40%), no underlying cause for OHCA was found during hospitalization despite profound diagnostics. Unknown-cause OHCA patients showed a higher prevalence of MAD compared to definite-cause patients (56% vs. 10%, p < 0.001) and had a MAD-extent of 6.3 mm (IQR: 4.4-10.3); moreover, these patients were significantly younger (43 years vs. 61 years, p < 0.001), more often female (74% vs. 21%, p < 0.001) and had fewer comorbidities (hypertension, hypercholesterolemia, coronary artery disease, all p < 0.005). By logistic regression analysis, the presence of MAD remained significantly associated with OHCA of unknown cause (odds ratio: 8.49, 95% confidence interval: 2.37-30.41, p = 0.001) after adjustment for age, presence of hypertension, and hypercholesterolemia. CONCLUSIONS: MAD is rather common in OHCA patients without definitive aetiology undergoing CMR. The presence of MAD was independently associated to OHCA without an identifiable trigger. Further research is needed to understand the exact role of MAD in OHCA patients.

Photon-Counting Detector Computed Tomography (PCD-CT): A New Era for Cardiovascular Imaging? Current Status and Future Outlooks.

Photon-counting detector computed tomography (PCD-CT) represents a revolutionary new generation of computed tomography (CT) for the imaging of patients with cardiovascular diseases. Since its commercial market introduction in 2021, numerous studies have identified advantages of this new technology in the field of cardiovascular imaging, including improved image quality due to an enhanced contrast-to-noise ratio, superior spatial resolution, reduced artifacts, and a reduced radiation dose. The aim of this narrative review was to discuss the current scientific literature, and to find answers to the question of whether PCD-CT has yet led to a true step-change and significant progress in cardiovascular imaging.

Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction.

BACKGROUND: Acute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). METHODS: In this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging. RESULTS: Median plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. CONCLUSION: High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI.

Functional aortic valve area differs significantly between sexes: A phase-contrast cardiac MRI study in patients with severe aortic stenosis.

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 cm2, IQR: 0.61-1.14 vs. 0.94 cm2, 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.

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. RESULTS: Intramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60-23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16). CONCLUSIONS: In STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications.

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

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

Temporal Trends in Infarct Severity Outcomes in ST-Segment-Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

Background Severity of myocardial tissue injury is a main determinant of morbidity and death related to ST-segment-elevation myocardial infarction (STEMI). Temporal trends of infarct characteristics at the myocardial tissue level have not been described. This study sought to assess temporal trends in infarct characteristics through a comprehensive assessment by cardiac magnetic resonance imaging at a standardized time point early after STEMI. Methods and Results We analyzed patients with STEMI treated with percutaneous coronary intervention at the University Hospital of Innsbruck who underwent cardiac magnetic resonance imaging between 2005 and 2021. The study period was divided into terciles. Myocardial damage characteristics were assessed using a multiparametric cardiac magnetic resonance imaging protocol within the first week after STEMI and compared between groups. A total of 843 patients with STEMI (17% women) with a median age of 57 (interquartile range, 51-66) years were analyzed. While age, sex, and the clinical risk profile expressed as thrombolysis in myocardial infarction risk score were comparable across the study period, there were differences in guideline-recommended therapies. At the same time, there was no significant change in infarct size (P=0.25), microvascular obstruction (P=0.50), and intramyocardial hemorrhage (P=0.34). Left ventricular remodeling indices and left ventricular ejection fraction remained virtually unchanged (all P>0.05). Major adverse cardiovascular events at 4 (interquartile range, 4-5) months were similar between groups (P=0.36). Conclusions In this magnetic resonance imaging study investigating patients with STEMI treated with primary percutaneous coronary intervention over the past 15 years, no change in infarct severity at the myocardial level has been observed. Clinical research on novel therapeutic approaches to reduce myocardial tissue injury should be a priority.

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

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

Slice positioning in phase-contrast MRI impacts aortic stenosis assessment.

AIMS: To determine the phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) slice-position above aortic leaflet-attachment-plane (LAP) that provides flow-velocity, -volume and aortic valve area (AVA) measurements with best agreement to invasive and echocardiographic measurements in aortic stenosis (AS). METHODS AND RESULTS: Fifty-five patients with moderate/severe AS underwent cardiac catheterization, transthoracic echocardiography (TTE) and CMR. Overall, 171 image-planes parallel to LAP were measured via PC-CMR between 22 mm below and 24 mm above LAP. AVA via PC-CMR was calculated as flow-volume divided by peak-velocity during systole. Stroke volume (SV) and AVA were compared to volumetric SV and invasive AVA via the Gorlin-formula, respectively. Above LAP, SV by PC-CMR showed no significant dependence on image-plane-position and correlated strongly with volumetry (rho: 0.633, p < 0.001, marginal-mean-difference (MMD): 1 ml, 95 % confidence-interval (CI): -4 to 6). AVA assessed in image-planes 0-10 mm above LAP differed significantly from invasive measurement (MMD: -0.14 cm2, 95 %CI: 0.08-0.21). In contrast, AVA-values by PC-CMR measured 10-20 mm above LAP showed good agreement with invasive determination without significant MMD (0.003 cm2, 95 %CI: -0.09 to 0.09). Within these measurements, a plane 15 mm above LAP resulted in the lowest bias (MMD: 0.02 cm2, 95 %CI:-0.29 to 0.33). SV and AVA via TTE correlated moderately with volumetry (rho: 0.461, p < 0.001; bias: 15 ml, p < 0.001) and cardiac catheterization (rho: 0.486, p < 0.001, bias: -0.13 cm2, p < 0.001), respectively. CONCLUSION: PC-CMR measurements at 0-10 mm above LAP should be avoided due to significant AVA-overestimation compared to invasive determination. AVA-assessment by PC-CMR between 10 and 20 mm above LAP did not differ from invasive measurements, with the lowest intermethodical bias measured 15 mm above LAP.

Prognostic value of pulmonary transit time by cardiac magnetic resonance imaging in ST-elevation myocardial infarction.

OBJECTIVES: To investigate the prognostic value of pulmonary transit time (pTT) determined by cardiac magnetic resonance (CMR) after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: Comprehensive CMR examinations were performed in 207 patients 3 days and 4 months after reperfused STEMI. Functional parameters and infarct characteristics were assessed. PTT was defined as the interval between peaks of gadolinium contrast time-intensity curves in the right and left ventricles in first-pass perfusion imaging. Cox regression models were calculated to assess the association between pTT and the occurrence of major adverse cardiac events (MACE), defined as a composite of death, re-infarction, and congestive heart failure. RESULTS: PTT was 8.6 s at baseline and 7.8 s at the 4-month CMR. In Cox regression, baseline pTT (hazard ratio [HR]: 1.58; 95% CI: 1.12 to 2.22; p = 0.009) remained significantly associated with MACE occurrence after adjustment for left ventricular ejection fraction (LVEF) and cardiac index. The association of pTT and MACE remained significant also after adjusting for infarct size and microvascular obstruction size. In Kaplan-Meier analysis, pTT ≥ 9.6 s was associated with MACE (p < 0.001). Addition of pTT to LVEF resulted in a categorical net reclassification improvement of 0.73 (95% CI: 0.27 to 1.20; p = 0.002) and integrated discrimination improvement of 0.07 (95% CI: 0.02 to 0.13; p = 0.007). CONCLUSIONS: After reperfused STEMI, CMR-derived pTT was associated with hard clinical events with prognostic information independent of and incremental to infarct size and LV systolic function. KEY POINTS: • Pulmonary transit time is the duration it takes the heart to pump blood from the right chambers across lung vessels to the left chambers. • This prospective single-centre study showed inferior outcome in patients with prolonged pulmonary transit time after myocardial infarction. • Pulmonary transit time assessed by magnetic resonance imaging added incremental information to established prognostic markers.

Safety and efficacy of direct cardiac shockwave therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial-an update.

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.

Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-In-Human Results of Shock Wave Therapy Prove Safety and Feasibility.

Background Spinal cord ischemia (SCI) remains a devastating complication after aortic dissection or repair. A primary hypoxic damage is followed by a secondary damage resulting in further cellular loss via apoptosis. Affected patients have a poor prognosis and limited therapeutic options. Shock wave therapy (SWT) improves functional outcome, neuronal degeneration and survival in murine spinal cord injury. In this first-in-human study we treated 5 patients with spinal cord ischemia with SWT aiming to prove safety and feasibility. Methods and Results Human neurons were subjected to ischemic injury with subsequent SWT. Reactive oxygen species and cellular apoptosis were quantified using flow cytometry. Signaling of the antioxidative transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) and immune receptor Toll-like receptor 3 (TLR3) were analyzed. To assess whether SWT act via a conserved mechanism, transgenic tlr3-/- zebrafish created via CRISPR/Cas9 were subjected to spinal cord injury. To translate our findings into a clinical setting, 5 patients with SCI underwent SWT. Baseline analysis and follow-up (6 months) included assessment of American Spinal Cord Injury Association (ASIA) impairment scale, evaluation of Spinal Cord Independence Measure score and World Health Organization Quality of Life questionnaire. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2-related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration. In a first-in-human study, we treated 5 patients with SCI using SWT (mean age, 65.3 years). Four patients presented with acute aortic dissection (80%), 2 of them exhibited preoperative neurological symptoms (40%). Impairment was ASIA A in 1 patient (20%), ASIA B in 3 patients (60%), and ASIA D in 1 patient (20%) at baseline. At follow-up, 2 patients were graded as ASIA A (40%) and 3 patients as ASIA B (60%). Spinal cord independence measure score showed significant improvement. Examination of World Health Organization Quality of Life questionnaires revealed increased scores at follow-up. Conclusions SWT reduces oxidative damage upon SCI via immune receptor TLR3. The first-in-human application proved safety and feasibility in patients with SCI. SWT could therefore become a powerful regenerative treatment option for this devastating injury.

Cardiac magnetic resonance imaging versus computed tomography to guide transcatheter aortic valve replacement: study protocol for a randomized trial (TAVR-CMR).

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.

Prevalence and prognostic impact of mitral annular disjunction in patients with STEMI - A cardiac magnetic resonance study.

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 ±â€¯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.

Evolution of Myocardial Tissue Injury: A CMR Study Over a Decade After STEMI.

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.

A novel approach to determine aortic valve area with phase-contrast cardiovascular magnetic resonance.

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 cm2), correlated moderately (r: 0.54, p < 0.001) with invasive AVA (0.70 ± 0.23 cm2), resulting in a small bias of 0.08 cm2 (LLoA and ULoA: - 0.36 cm2 and 0.55 cm2, p = 0.017). Inter-methodically, AVA by TTE (0.81 ± 0.23 cm2) compared to invasive determination showed similar correlations (r: 0.58, p < 0.001 with a bias of 0.11 cm2, 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.

Impact of COVID-19 pandemic restrictions on ST-elevation myocardial infarction: a cardiac magnetic resonance imaging study.

AIMS: The severity of myocardial tissue damage following ST-elevation myocardial infarction (STEMI) strongly determines short- and long-term prognosis. This study explored the impact of the coronavirus disease 2019 (COVID-19) pandemic and associated public health restrictions on infarct severity. METHODS AND RESULTS: STEMI patients treated with primary percutaneous coronary intervention (PCI) and included in the prospective Magnetic Resonance Imaging in Acute ST-Elevation Myocardial Infarction (MARINA-STEMI) cohort study from 2015- 2020 (n = 474) were categorized according to (i) timeframes with and without major public health restrictions in 2020, and (ii) timeframes of major public health restrictions during 2020 and during the corresponding timeframes between 2015-2019. Myocardial damage was evaluated by cardiac magnetic resonance imaging. During major public health restrictions in 2020 (n = 48), there was an increase in infarct size (22 [IQR 12-29] vs. 14 [IQR 6-23]%, P < 0.01), a higher frequency (77% vs. 52%, P < 0.01) and larger extent of microvascular obstruction (1.5 [IQR 0.1-11.4] vs. 0.2 [IQR 0.0-2.6]%, P < 0.01) and a higher rate of intramyocardial haemorrhage (56% vs. 34%, P = 0.02) as compared to the phases without major restrictions in 2020 (n = 101). These findings were confirmed in adjusted analysis and were consistent when comparing patients admitted in 2020 versus patients admitted in the "pre-pandemic" era (2015-2019). Patient characteristics were comparable between groups, except for a significantly longer total ischemia time (P < 0.01) and higher frequency of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow 0 during times of major restrictions (P = 0.03). CONCLUSION: This study provides novel mechanistic insights demonstrating a significant increase in myocardial damage in STEMI patients admitted during the COVID-19 pandemic with a temporal relation to major public health restrictions.

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

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