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.

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.

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.

Skeletal Muscle Disorders: A Noncardiac Source of Cardiac Troponin T.

BACKGROUND: Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs). METHODS: We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT-Elecsys) and 3 hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, TNNT/I1-3 mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD. RESULTS: Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all P<0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7-32.5 ng/L] versus 5 ng/L [IQR, 3-9 ng/L]; P<0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI-Architect, 2.5 ng/L [IQR, 1.2-6.2 ng/L] versus 2.9 ng/L [IQR, 1.8-5.0 ng/L]; hs-cTnI-Access, 3.3 ng/L [IQR, 2.4-6.1 ng/L] versus 2.7 ng/L [IQR, 1.6-5.0 ng/L]; and hs-cTnI-Vista, 7.4 ng/L [IQR, 5.2-13.4 ng/L] versus 7.5 ng/L [IQR, 6-10 ng/L]). hs-cTnT-Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (P<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of TNNT2, encoding cTnT (but none for TNNI3, encoding cTnI) versus control subjects (n=16, PWald<0.001); the expression correlated with pathological disease activity (R=0.59, Pt-statistic<0.001) and circulating hs-cTnT concentrations (R=0.26, Pt-statistic=0.031). CONCLUSIONS: In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03660969.

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.

Only one beer can be mortal: a case report of two sisters with cardiac arrest due to a homozygous mutation in PPA2 gene.

We report the long way to the correct diagnosis in two teenage sisters who developed a cardiac arrest after consuming minimal amounts of alcohol. The older girl dramatically survived two cardiac arrests at the age of 14 and 15 years. She underwent an extensive examination that revealed isolated cardiac abnormalities including fibrosis, dilated cardiomyopathy and inflammation. The younger girl also had a cardiac arrest at the age of 15 and died suddenly after consuming 1-2 beers, 3 years after her sister´s first incident. Autopsy of the heart revealed acute myocarditis without structural alterations. Multigene panel analysis (not including PPA2) showed SCN5A and CACNA1D variants in both sisters and their healthy mother. Six years later duo exome allowed the diagnosis of an autosomal recessive PPA2-related mitochondriopathy. We discuss the molecular results and clinical picture of our patients compared to other PPA2-related cases. We highlight the diagnostic contribution of multigene panels and exome analysis. The genetic diagnosis is important for medical care and for everyday life, specifically because alcohol intake can result in cardiac arrest and should be strictly avoided.   Conclusion: Duo exome sequencing clarified the diagnosis of PPA2-related mitochondriopathy in two sisters with isolated cardiac features and sudden cardiac arrest triggered by minimal amounts of alcohol. What is Known: • Multigene-Panel or exome analysis is a valuable tool to identify genetic causes of hereditary cardiac arrhythmias. • Variants of unknown significance can lead to misinterpretation. PPA2-related mitochondriopathy is a very rare autosomal recessive condition that is normally fatal in infancy. What is New: • Duo exome analysis in two teeenage sisters with cardiac arrest revealed a homozygous mild PPA2 mutation as the underlying pathology restricted to the heart muscle.

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.

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.

Baseline LV ejection fraction by cardiac magnetic resonance and 2D echocardiography after ST-elevation myocardial infarction - influence of infarct location and prognostic impact.

OBJECTIVES: The comparability of left ventricular ejection fraction (LVEF) measurements by cardiac magnetic resonance (CMR) and 2D echocardiography (2DE) early after ST-elevation myocardial infarction (STEMI) remains unclear. METHODS: In this study, LVEF measured by CMR and 2DE (Simpson's method) were compared in 221 patients after STEMI treated by primary percutaneous coronary intervention. 2DE image quality was systematically assessed and studies reported by an accredited examiner. Intermodality agreement was assessed by the Bland-Altman method. Major adverse cardiac events (MACE) were defined as the composite of death, myocardial infarction or hospitalisation for heart failure. Patients were followed up for a median of 40.9 months (IQR 28.1-56). RESULTS: After non-anterior STEMI, LVEF measurements by 2DE (single and biplane) were consistently underestimated in comparison to CMR (CMR 55.7 ± 9.5% vs. 2DE-4CV 49 ± 8.2% (p = 0.06), 2DE-2CV 52 ± 8% (p < 0.001), 2DE-biplane 53.5 ± 7.1% (p = 0.01)). After anterior STEMI, there was no significant difference in LVEF measurements by 2DE and CMR with acceptable limits of agreement (CMR 49 ± 11% vs. 2DE-4CV 49 ± 8.2% (p = 0.8), 2DE-2CV 49 ± 9.2% (p = 0.9), 2DE-biplane 49.6 ± 8% (p = 0.5)). In total, 15% of patients experienced a MACE during follow-up. In multivariate Cox regression analysis, reduced LVEF (< 52%) as assessed by either 2DE or CMR was predictive of MACE (2DE HR = 2.57 (95% CI 1.1-6.2), p = 0.036; CMR HR = 2.51 (95% CI 1.1-5.7), p = 0.028). CONCLUSIONS: At baseline after non-anterior STEMI, 2D echocardiography significantly underestimated LVEF in comparison to CMR, whereas after anterior infarction, measurements were within acceptable limits of agreement. Both imaging modalities offered similar prognostic values when a reduced LVEF < 52% was applied. KEY POINTS: • After non-anterior STEMI, 2D-echocardiography significantly underestimated LVEF compared with cardiac MRI • An ejection fraction of < 52% in the acute post-infarct period by both 2D echocardiography and CMR offered similar prognostic values.

Non-contrast MRI protocol for TAVI guidance: quiescent-interval single-shot angiography in comparison with contrast-enhanced CT.

OBJECTIVES: To prospectively compare unenhanced quiescent-interval single-shot MR angiography (QISS-MRA) with contrast-enhanced computed tomography angiography (CTA) for contrast-free guidance in transcatheter aortic valve intervention (TAVI). METHODS: Twenty-six patients (mean age 83 ± 5 years, 15 female [58%]) referred for TAVI evaluation underwent QISS-MRA for aortoiliofemoral access guidance and non-contrast three-dimensional (3D) "whole heart" MRI for prosthesis sizing on a 1.5-T system. Contrast-enhanced CTA was performed as imaging gold standard for TAVI planning. Image quality was assessed by a 4-point Likert scale; continuous MRA and CTA measurements were compared with regression and Bland-Altman analyses. RESULTS: QISS-MRA and CTA-based measurements of aortoiliofemoral vessel diameters correlated moderately to very strong (r = 0.572 to 0.851, all p ≤ 0.002) with good to excellent inter-observer reliability (intra-class correlation coefficient (ICC) = 0.862 to 0.999, all p < 0.0001) regarding QISS assessment. Mean diameters of the infrarenal aorta and iliofemoral vessels differed significantly (bias 0.37 to 0.98 mm, p = 0.041 to < 0.0001) between the two modalities. However, inter-method decision for transfemoral access route was comparable (κ = 0.866, p < 0.0001). Aortic root parameters assessed by 3D whole heart MRI strongly correlated (r = 0.679 to 0.887, all p ≤ 0.0001) to CTA measurements. CONCLUSION: QISS-MRA provides contrast-free access route evaluation in TAVI patients with moderate to strong correlations compared with CTA and substantial inter-observer agreement. Despite some significant differences in minimal vessel diameters, inter-method agreement for transfemoral accessibility is strong. Combination with 3D whole heart MRI facilitates unenhanced TAVI guidance. KEY POINTS: • QISS-MRA and CTA inter-method agreement for transfemoral approach is strong. • QISS-MRA is a very good alternative to CTA and MRA especially in patients with Kidney Disease Outcomes Quality Initiativestages 4 and 5. • Combination of QISS-MRA and 3D "whole heart" MRI facilitates fully unenhanced TAVI guidance.

Mitral annular plane systolic excursion by cardiac MR is an easy tool for optimized prognosis assessment in ST-elevation myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the comparative prognostic value of mitral annular plane systolic excursion (MAPSE) versus left ventricular ejection fraction (LVEF), measured by cardiac magnetic resonance (CMR) imaging in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS: CMR was performed in 255 STEMI patients within 2 days (interquartile range (IQR) 2-4 days) after infarction. CMR included MAPSE measurement on CINE 4-chamber view. Patients were followed for major adverse cardiovascular events (MACE)-death, non-fatal myocardial re-infarction, stroke, and new congestive heart failure. RESULTS: Patients with MACE (n = 35, 14%, median follow-up 3 years [IQR 1-4 years]) showed significantly lower MAPSE (8 mm [7-8.8] vs. 9.6 mm [8.1-11.5], p < 0.001). The association between decreased MAPSE (< 9 mm, optimal cut-off value by c-statistics) remained significant after adjustment for independent clinical and CMR predictors of MACE. The AUC of MAPSE for the prediction of MACE was 0.74 (CI 95% 0.65-0.82), significantly higher than that of LVEF (0.61 [CI 95% 0.50-0.71]; p < 0.001). CONCLUSIONS: Reduced long-axis function assessed with MAPSE measurement using CINE CMR independently predicts long-term prognosis following STEMI. Moreover, MAPSE provided significantly higher prognostic implication in comparison with conventional LVEF measurement. KEY POINTS: • MAPSE determined by CMR independently predicts long-term prognosis following STEMI. • MACE-free survival is significantly higher in patients with MAPSE ≥ 9 mm than < 9 mm. • MAPSE provides significantly higher prognostic implication than conventional LVEF.

Prognosis-based definition of left ventricular remodeling after ST-elevation myocardial infarction.

OBJECTIVES: Cardiac magnetic resonance (CMR) is the gold-standard modality for the assessment of left ventricular (LV) remodeling in ST-elevation myocardial infarction (STEMI) patients. However, the commonly used remodeling criteria have never been validated for hard clinical events. We therefore aimed to define clear CMR criteria of LV remodeling following STEMI with proven prognostic impact. METHODS: This observational study included 224 patients suffering from acute STEMI. CMR was performed within 1 week and 4 months after infarction to evaluate different remodeling criteria including relative changes in LV end-diastolic volume (%∆LVEDV), end-systolic volume (%∆LVESV), ejection fraction (%∆LVEF), and myocardial mass (%∆LVMM). Primary endpoint was the occurrence of major adverse cardiovascular events (MACE) including all-cause death, re-infarction, stroke, and new congestive heart failure 24 months following STEMI. Secondary endpoint was defined as composite of primary endpoint and cardiovascular hospitalization. The Mann-Whitney U test was applied to assess differences in LV remodeling measures between patients with and without MACE. Values for the prediction of primary and secondary endpoints were assessed by c-statistics and Cox regression analysis. RESULTS: The incidence of MACE (n = 13, 6%) was associated with higher %∆LVEDV (p = 0.002) and %∆LVMM (p = 0.02), whereas %∆LVESV and %∆LVEF were not significantly related to MACE (p > 0.05). The area under the curve (AUC) for the prediction of MACE was 0.76 (95% confidence interval [CI], 0.65-0.87) for %∆LVEDV (optimal cut-off 10%) and 0.69 (95%CI, 0.52-0.85) for %∆LVMM (optimal cut-off 5%). From all remodeling criteria, %∆LVEDV ≥ 10% showed highest hazard ratio (8.68 [95%CI, 2.39-31.56]; p = 0.001) for MACE. Regarding secondary endpoint (n = 35, 16%), also %∆LVEDV with an optimal threshold of 10% emerged as strongest prognosticator (AUC 0.66; 95%CI, 0.56-0.75; p = 0.004). CONCLUSIONS: Following revascularized STEMI, %∆LVEDV ≥ 10% showed strongest association with clinical outcome, suggesting this criterion as preferred CMR-based definition of post-STEMI LV remodeling. KEY POINTS: • CMR-determined %∆LVEDV and %∆LVMM were significantly associated with MACE following STEMI. • Neither %∆LVESV nor %∆LVEF showed a significant relation to MACE. • %∆LVEDV ≥ 10 was revealed as LV remodeling definition with highest prognostic validity.

Complete versus simplified Selvester QRS score for infarct severity assessment in ST-elevation myocardial infarction.

BACKGROUND: Complete and simplified Selvester QRS score have been proposed as valuable clinical tool for estimating myocardial damage in patients with ST-elevation myocardial infarction (STEMI). We sought to comprehensively compare both scoring systems for the prediction of myocardial and microvascular injury assessed by cardiac magnetic resonance (CMR) imaging in patients with acute STEMI. METHODS: In this prospective observational study, 201 revascularized STEMI patients were included. Electrocardiography was conducted at a median of 2 (interquartile range 1-4) days after the index event to evaluate the complete and simplified QRS scores. CMR was performed within 1 week and 4 months thereafter to determine acute and chronic infarct size (IS) as well as microvascular obstruction (MVO). RESULTS: Complete and simplified QRS score showed comparable predictive value for acute (area under the curve (AUC) = 0.64 vs. 0.67) and chronic IS (AUC = 0.63 vs. 0.68) as well as for MVO (AUC = 0.64 vs. 0.66). Peak high sensitivity cardiac troponin T (hs-cTnT) showed an AUC of 0.88 for acute IS and 0.91 for chronic IS, respectively. For the prediction of MVO, peak hs-cTnT represented an AUC of 0.81. CONCLUSIONS: In reperfused STEMI, complete and simplified QRS score displayed comparable value for the prediction of acute and chronic myocardial as well as microvascular damage. However, both QRS scoring systems provided inferior predictive validity, compared to peak hs-cTnT, the clinical reference method for IS estimation.

Novel implant-free loop Tenodesis vs. simple Tenotomy of the long biceps tendon - a biomechanical investigation.

BACKGROUND: Simple tenotomy and anchor tenodesis are commonly used in treatment of long biceps tendon (LHB) pathologies. The tenotomy can result in biceps distalization or cosmetic deformities. A novel loop Tenodesis Technique (LTD) could prevent a distalization of the biceps muscle without the risk of implant associated complications. The purpose of this study was to investigate the biomechanical aspects of the novel LTD compared to a standard tenotomy of the LHB. It has been hypothesized that the novel technique will show biomechanical superiority in terms of resistance and distalization. METHODS: Seven paired adult human cadaveric shoulder joints were assigned to one of the two study groups: Loop tenodesis (LTD); simple tenotomy (STT). In both groups load-to-failure testing was performed. The load-displacement curve was used to determine the maximum load (N), the degree of distalization of the LHB (mm) and the stiffness (N/mm). Additionally, the mode of failure was registered. RESULTS: The LTD group achieved a significantly higher ultimate load to failure (LTD: 50.5 ± 12.5 N vs. STT: 6.6 ± 3.9 N; p = 0.001). Significantly less distalization of the tendon could be detected for the LTD group (LTD: 8 ± 2.3 mm vs. STT: 22.4 ± 2.4 mm; p = 0.001). Stiffness was 7.4 ± 3.9 N/mm for the LTD group and 0.23 ± 0.16 N/mm for the STT group (p = 0.001). In all specimens of the LTD group a tendon rupture was found as mode of failure, while the STT group failed because of pulling out the LHB through the bicipital groove. CONCLUSION: The novel loop Tenodesis Technique shows biomechanically higher stability as well as less distalization compared to a simple tenotomy of the long biceps tendon.

A Cytokine-Like Protein Dickkopf-Related Protein 3 Is Atheroprotective.

BACKGROUND: Dickkopf-related protein 3 (DKK3) is a secreted protein that is involved in the regulation of cardiac remodeling and vascular smooth muscle cell differentiation, but little is known about its role in atherosclerosis. METHODS: We tested the hypothesis that DKK3 is atheroprotective using both epidemiological and experimental approaches. Blood DKK3 levels were measured in the Bruneck Study in 2000 (n=684) and then in 2005 (n=574). DKK3-deficient mice were crossed with apolipoprotein E-/- mice to evaluate atherosclerosis development and vessel injury-induced neointimal formation. Endothelial cell migration and the underlying mechanisms were studied using in vitro cell culture models. RESULTS: In the prospective population-based Bruneck Study, the level of plasma DKK3 was inversely related to carotid artery intima-media thickness and 5-year progression of carotid atherosclerosis independently from standard risk factors for atherosclerosis. Experimentally, we analyzed the area of atherosclerotic lesions, femoral artery injury-induced reendothelialization, and neointima formation in both DKK3-/-/apolipoprotein E-/- and DKK3+/+/apolipoprotein E-/- mice. It was demonstrated that DKK3 deficiency accelerated atherosclerosis and delayed reendothelialization with consequently exacerbated neointima formation. To explore the underlying mechanisms, we performed transwell and scratch migration assays using cultured human endothelial cells, which exhibited a significant induction in cell migration in response to DKK3 stimulation. This DKK3-induced migration activated ROR2 and DVL1, activated Rac1 GTPases, and upregulated JNK and c-jun phosphorylation in endothelial cells. Knockdown of the ROR2 receptor using specific siRNA or transfection of a dominant-negative form of Rac1 in endothelial cells markedly inhibited cell migration and downstream JNK and c-jun phosphorylation. CONCLUSIONS: This study provides the evidence for a role of DKK3 in the protection against atherosclerosis involving endothelial migration and repair, with great therapeutic potential implications against atherosclerosis.

Is MRI equivalent to CT in the guidance of TAVR? A pilot study.

OBJECTIVES: To compare a comprehensive cardiovascular magnetic resonance imaging (MRI) protocol with contrast-enhanced computed tomography angiography (CTA) for guidance in transcatheter aortic valve replacement (TAVR) evaluation. METHODS AND RESULTS: Non-contrast three-dimensional (3D) 'whole heart' MRI imaging for aortic annulus sizing and measurements of coronary ostia heights, contrast-enhanced MRI angiography (MRA) for evaluation of transfemoral routes as well as aortoiliofemoral-CTA were performed in 16 patients referred for evaluation of TAVR. Aortic annulus measurements by MRI and CTA showed a very strong correlation (r=0.956, p<0.0001; effective annulus area for MRI 430±74 vs. 428±78 mm2 for CTA, p=0.629). Regarding decision for valve size there was complete consistency between MRI and CTA. Moreover, vessel luminal diameters and angulations of aortoiliofemoral access as measured by MRA and CTA showed overall very strong correlations (r= 0.819 to 0.996, all p<0.001), the agreement of minimal vessel diameter between the two modalities revealed a bias of 0.02 mm (upper and lower limit of agreement: 1.02 mm and -0.98 mm). CONCLUSIONS: In patients referred for TAVR, MRI measurements of aortic annulus and minimal aortoiliofemoral diameters showed good to excellent agreement. Decisions based on MRI measurements regrading prosthesis sizing and transfemoral access would not have modified TAVR-strategy as compared to a CTA-based choice. KEY POINTS: • 'Whole heart' MRI and CTA measurements of aortic annulus correlate very strongly. • MRI- and CTA-based prostheses sizing are in excellent agreement. • MRA and CTA equally guide TAVR access strategy.

Acute kidney injury is associated with microvascular myocardial damage following myocardial infarction.

Acute kidney injury (AKI) is a frequent complication in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention. However, the pathophysiology of AKI in this setting is complex and goes beyond the administration of contrast media. Studies assessing the impact of infarct characteristics on AKI are currently lacking. Therefore, we investigated the association of AKI with myocardial as well as microvascular injury in an initial total of 361 consecutive STEMI patients treated by primary percutaneous coronary intervention. Of these, 318 patients were included in final analysis. Serum creatinine was measured on admission as well as 24, 48, and 72 hours thereafter with AKI defined as an increase in serum creatinine of 0.3 mg/dl or more. Cardiac magnetic resonance (CMR) scans were performed in the first week after infarction, with microvascular injury visualized by late gadolinium enhancement CMR defined as any region of hypoenhancement within the hyperenhanced area of infarction. Sixteen patients developed AKI. They showed significantly lower left ventricular ejection fraction (45[interquartile range 40-52]% vs. 54[47-59]%), larger infarct size (21[15-35]% vs. 12[7-22]%) of left ventricular myocardial mass, and more frequent microvascular injury (81 vs. 46%) than those free of AKI. Meaningfully, in multivariate analysis including all CMR data, microvascular injury was the sole independent predictor of AKI (odds ratio 6.74, 95% confidence interval of 1.49-30.43). Thus, among revascularized STEMI patients, the presence of microvascular injury assessed by CMR was independently associated with an increased risk of AKI. This suggests a potential pathophysiological link between cardiac microvascular disease and renal injury following STEMI.

Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: • RA patients had higher T1, ECV and T2 values compared to controls. • Most significant differences were observed for T2. • Our results seem to be independent of the presence of LGE. • Mapping might be useful in the evaluation of myocardial involvement in RA.

T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

BACKGROUND: Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. METHODS: Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. RESULTS: Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. CONCLUSION: AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

Novel biomarkers predicting cardiac function after acute myocardial infarction.

BACKGROUND: Measurement of biomarkers provides a cost-effective and widely available method to estimate cardiac dysfunction and clinical outcome of patients with acute myocardial infarction (AMI). SOURCES OF DATA: PubMed entries with terms 'myocardial infarction' and the respective biomarker. AREAS OF AGREEMENT: Cardiac troponins and natriuretic peptides are closely related to left ventricular dysfunction and the occurrence of adverse clinical events following AMI. AREAS OF CONTENTION: The incremental value of novel biomarkers is controversial. FUTURE DIRECTIONS: The combination of traditional and novel biomarkers might further improve risk stratification of patients with AMI. SEARCH STRATEGY: We searched all entries on the PubMed database with the MeSH terms 'myocardial infarction' and 'cardiac troponins', 'natriuretic peptides', 'copeptin', galectin-3', 'corin', 'fetuin-A', 'adiponectin' and 'microRNA'.