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Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies. Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis. Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I2 = 69%). Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.

Early and late microvascular obstruction (MVO) assessed by cardiovascular magnetic resonance (CMR) are prognostic markers for short-term clinical endpoints after acute ST-elevation myocardial infarction (STEMI). However, there is a lack of studies with long-term follow-up periods (>24 months). STEMI patients reperfused by primary angioplasty (n = 129) underwent MRI at a median of 2 days after the index event. Early MVO was determined on dynamic Gd first-pass images directly after the administration of 0.1 mmol/kg bodyweight Gd-based contrast agent. Furthermore, ejection fraction (EF, %), left ventricular myocardial mass (LVMM) and total infarct size (% of LVMM) were determined with CMR. Clinical follow-up was conducted after a median of 52 months. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization. Follow-up was completed by 107 patients. 63 pre-defined events occurred during follow-up. Initially, 74 patients showed early MVO. Patients with early MVO had larger infarcts (mean: 24.9 g vs. 15.5 g, p = 0.002) and a lower EF (mean: 39% vs. 46%, p = 0.006). The primary endpoint occurred in 66.2% of patients with MVO and in 42.4% of patients without MVO (p < 0.05). The presence of early MVO was associated with a reduced event-free survival (log-rank p < 0.05). Early MVO was identified as the strongest independent predictor for the occurrence of the primary endpoint in the multivariable Cox regression analysis adjusting for age, ejection fraction and infarct size (hazard ratio: 2.79, 95%-CI 1.25-6.25, p = 0.012). Early MVO, as assessed by first-pass CMR, is an independent long-term prognosticator for morbidity after AMI.

ObjectiveAdverse left ventricular (LV) remodelling is the major determinant of heart failure and mortality in survivors of ST-elevation myocardial infarction (STEMI). The role of fibroblast growth factor 23 (FGF-23) for LV remodelling prediction after STEMI is unknown. We therefore aimed to investigate the relation between circulating FGF-23 and LV remodelling following revascularised STEMI.MethodsIn this prospective observational study, we included 88 consecutive patients with STEMI treated by primary percutaneous coronary intervention. FGF-23 concentrations were measured 2 (IQR: 2–2) days after symptom onset. Cardiac magnetic resonance was performed 2 (IQR: 1–3) days as well as 4 (IQR: 4–5) months after infarction to evaluate LV remodelling, defined as ≥20% increase in LV end-diastolic volume.ResultsLevels of FGF-23 were significantly higher in patients who developed LV remodelling (n=11, 13%) as compared with those without LV remodelling (152.6 (102.5–241.3) vs 75.8 (58.6–105.4) relative units per millilitre, p=0.002). The association between FGF-23 and LV remodelling remained significant (OR: 14.1, 95% CI 2.8 to 70.9; p=0.001) after adjustment for biomarkers reflecting myocardial necrosis (high-sensitivity cardiac troponin T (hs-cTnT)), myocardial stress (N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammatory state (high-sensitivity C reactive protein (hs-CRP)). Moreover, a multimarker approach adding FGF-23 to the established LV remodelling-predictive biomarkers (hs-cTnT, NT-proBNP and hs-CRP) led to a net reclassification improvement of 0.92 (95% CI 0.44 to 1.41, p<0.001) and to an integrated discrimination improvement of 0.16 (95% CI 0.08 to 0.24, p<0.001).ConclusionsCirculating FGF-23 is independently associated with LV remodelling after reperfused STEMI. A comprehensive multimarker strategy that includes FGF-23 provides incremental prognostic value for prediction of LV remodelling.

Transcatheter aortic valve replacement (TAVR) is the preferred treatment for older patients with severe aortic stenosis with outcomes influenced by age and sex. Computed tomography (CT) is the reference imaging modality for TAVR planning, while cardiovascular magnetic resonance (CMR) is an emerging alternative for this indication. The aim of this study was to evaluate the impact of age and sex on implantation success in patients undergoing CT- or CMR-guided TAVR. This was a secondary analysis of the randomized TAVR-CMR trial comparing TAVR planning by CT or CMR (NCT03831087). Patients were categorized according to the median age (82 years) and sex. Implantation success, defined using the Valve Academic Research Consortium-2 definition (absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance), was compared at hospital discharge between age groups and sex for each imaging strategy. All-cause mortality at 6 months was compared between imaging strategies across age groups and sex. A total of 267 patients (median age 82 [IQR 80–85] years, 50% (133/267) female) underwent TAVR at two heart centers in Austria between September 2017 and December 2022. Implantation success did not differ significantly between imaging strategies across age and sex subgroups. For patients ≤82 years, success rates were 92.1% (58/63) (CT) vs. 94.7% (72/76) (CMR) (p=0.524), and for those >82 years, 89.4% (59/66) (CT) vs. 91.9% (57/62) (CMR) (p=0.622). Among female patients, success rates were 84.7% (50/59) (CT) vs. 93.2% (69/74) (CMR) (p=0.113), and among male patients, 95.7% (67/70) (CT) vs. 93.8% (60/64) (CMR) (p=0.610). All-cause mortality at 6 months did not differ significantly between imaging strategies across age and sex subgroups. Mortality rates for patients ≤82 and >82 years were 4.8% (3/63) vs. 5.3% (4/76) (p=0.839) and 9.1% (6/66) vs. 12.9% (8/62) (p=0.490) for CT and CMR, respectively. Similarly, female and male patients had comparable mortality rates (10.2% (6/59) vs. 8.1% (6/74), p=0.680; 4.3% (3/70) vs. 9.4% (6/64), p=0.240). In this secondary analysis of the TAVR-CMR trial, CMR-guided TAVR was associated with similar outcomes compared with CT-guided TAVR irrespective of age and sex. [Display omitted]

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). 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. 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). 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. [Display omitted]

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.

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure for treating severe aortic stenosis, where optimal vascular access route selection is critical to reduce complications. It requires careful selection of the iliac artery with the most favourable anatomy, specifically, one with the largest diameters and no segments narrower than 5 mm. This process is time-consuming when carried out manually. We present an active learning-based segmentation framework for contrast-enhanced Cardiac Magnetic Resonance (CMR) data, guided by probabilistic uncertainty and pseudo-labelling, enabling efficient segmentation with minimal manual annotation. The segmentations are then fed into an automated pipeline for diameter quantification, achieving a Dice score of 0.912 and a mean absolute percentage error (MAPE) of 4.92%. An ablation study using pre- and post-contrast CMR showed superior performance with post-contrast data only. Overall, the pipeline provides accurate segmentation and detailed diameter profiles of the aorto-iliac route, helping the assessment of the access route.

Bone defects can be filled with autografts, allografts and artificial bone-materials. The aim of this study was to evaluate whether the digitization of known defect models with a navigation system is a reliable measurement method for estimating the size of a bone defect. Six preformed, cylindrical and cone-shaped defects on an artificial hip-bone were digitalized by six different observers. Reference volumes were gathered by measuring the depth of the defects, using an alginate impression material to fill out the defects and calculating the volumes from a CT scan. One out of the six preformed defects showed a statistically significant difference between the digitalization and the calculation, four showed a significant difference between the digitalization and the mould as well as between the digitalization and the CT calculation. This technique offers satisfactory results and consistent reproducibility when digitalizing big defects with relatively simple shape. Decreasing size and increasing complexity of the defects leads to more imprecise measurements. •Digitalization of bone defects is possible using navigation systems.•This technique shows good results and reproducibility when measuring big defects.•The known size of a defect can be used to determine further treatment.

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.

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.