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.

Clinical Outcomes Associated With Various Microvascular Injury Patterns Identified by CMR After STEMI.

BACKGROUND: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known. OBJECTIVES: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients. METHODS: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+). RESULTS: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001). CONCLUSIONS: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI.

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.

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.

Culprit Lesion Vessel Size and Risk of Reperfusion Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

BACKGROUND: Microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) are well-established imaging biomarkers of failed myocardial tissue reperfusion in patients with ST-segment elevation-myocardial infarction treated with percutaneous coronary intervention. MVO and IMH are associated with an increased risk of adverse outcome independent of infarct size, but whether the size of the culprit lesion vessel plays a role in the occurrence and severity of reperfusion injury is currently unknown. This study aimed to evaluate the association between culprit lesion vessel size and the occurrence and severity of reperfusion injury as determined by cardiac magnetic resonance imaging. METHODS AND RESULTS: Patients (n=516) with first-time ST-segment-elevation myocardial infarction underwent evaluation with cardiac magnetic resonance at 4 (3-5) days after infarction. MVO was assessed with late gadolinium enhancement imaging and IMH with T2* mapping. Vessel dimensions were determined using catheter-based reference. Median culprit lesion vessel size was 3.1 (2.7-3.6) mm. MVO and IMH were found in 299 (58%) and 182 (35%) patients. Culprit lesion vessel size was associated with body surface area, diabetes, total ischemic time, postinterventional thrombolysis in myocardial infarction flow, and infarct size. There was no association between vessel size and MVO or IMH in univariable and multivariable analysis (P>0.05). These findings were consistent across patient subgroups with left anterior descending artery and non-left anterior descending artery infarctions and those with thrombolysis in myocardial infarction 3 flow post-percutaneous coronary intervention. CONCLUSIONS: Comprehensive characterization of myocardial tissue reperfusion injury by cardiac magnetic resonance revealed no association between culprit lesion vessel size and the occurrence of MVO and IMH in patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.

Correlation of 99mTc-DPD bone scintigraphy with histological amyloid load in patients with ATTR cardiac amyloidosis.

BACKGROUND: The significance of measuring 99mTc-labelled-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in transthyretin (ATTR) cardiac amyloidosis has not been adequately studied. This single-centre observational study evaluated the correlation between 99mTc-DPD scintigraphy and histological amyloid load in endomyocardial biopsy (EMB). METHODS: Twenty-eight patients with biopsy-proven ATTR amyloidosis and concomitantly available 99mTc-DPD scintigraphy were included. Visual Perugini scoring, and (semi-)quantitative analysis of cardiac 99mTc-DPD uptake by planar whole-body imaging and single photon emission computed tomography (SPECT/CT) using regions of interest (ROI) were performed. From this, heart-to-whole-body ratio (H/WB) and heart-to-contralateral-chest ratio (H/CL) were calculated. The histological amyloid load was quantified using two different staining methods. RESULTS: Increased cardiac tracer uptake was documented in all patients (planar: ROImean 129 ± 37 cps; SPECT/CT: ROImean 369 ± 142 cps). Histological amyloid load (19 ± 13%) significantly correlated with Perugini score (r = 0.69, p < .001) as well as with cardiac 99mTc-DPD uptake (planar: r = 0.64, p < .001; H/WB: r = 0.50, p = .014; SPECT/CT: r = 0.53, p = .008; H/CL: r = 0.43, p = .037) (results are shown for correlations with Congo Red-staining). CONCLUSION: In ATTR, cardiac 99mTc-DPD uptake significantly correlated with histological amyloid load in EMB. Further studies are needed to implement thresholds in cardiac 99mTc-DPD uptake measurements for risk stratification and guidance of therapy.

Infarct severity and outcomes in ST-elevation myocardial infarction patients without standard modifiable risk factors - A multicenter cardiac magnetic resonance study.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs) are well-established players in the pathogenesis of ST-elevation myocardial infarction (STEMI). However, in a significant proportion of STEMI patients, no SMuRFs can be identified, and the outcomes of this subgroup are not well described. OBJECTIVES: To assess the infarct characteristics at myocardial-tissue level and subsequent clinical outcomes in SMuRF-less STEMIs. METHODS: This multicenter, individual patient-data analysis included 2012 STEMI patients enrolled in four cardiac magnetic resonance (CMR) imaging studies conducted in Austria, Germany, Scotland, and the Netherlands. Unstable patients at time of CMR (e.g. cardiogenic shock/after cardiac arrest) were excluded. SMuRF-less was defined as absence of hypertension, smoking, hypercholesterolemia, and diabetes mellitus. All patients underwent CMR 3(interquartile range [IQR]:2-4) days after infarction to assess left ventricular (LV) volumes and ejection fraction, infarct size and microvascular obstruction (MVO). Clinical endpoints were defined as major adverse cardiovascular events (MACE), including all-cause mortality, re-infarction and heart failure. RESULTS: No SMuRF was identified in 185 patients (9%). These SMuRF-less patients were older, more often male, had lower TIMI risk score and pre-interventional TIMI flow, and less frequently multivessel-disease. SMuRF-less patients did not show significant differences in CMR markers compared to patients with SMuRFs (all p > 0.10). During a median follow-up of 12 (IQR:12-27) months, 199 patients (10%) experienced a MACE. No significant difference in MACE rates was observed between SMuRF-less patients and patients with SMuRFs (8vs.10%, p = 0.39). CONCLUSIONS: In this large individual patient-data pooled analysis of low-risk STEMI patients, infarct characteristics and clinical outcomes were not different according to SMuRF status.

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.

Visualization of the SyncAV® Algorithm for CRT Optimization by Non-invasive Imaging of Cardiac Electrophysiology: NICE-CRT Trial.

(1) Background: Periodic repetitive AV interval optimization using a device-based algorithm in cardiac resynchronization therapy (CRT) devices may improve clinical outcomes. There is an unmet need to successfully transform its application into clinical routine. (2) Methods: Non-invasive imaging of cardiac electrophysiology was performed in different device programming settings of the SyncAV® algorithm in 14 heart failure patients with left bundle branch block and a PR interval ≤ 250 milliseconds to determine the shortest ventricular activation time. (3) Results: the best offset time (to be manually programmed) permitting automatic dynamic adjustment of the paced atrioventricular interval after every 256 heart beats was found to be 30 and 50 milliseconds, decreasing mean native QRS duration from 181.6 ± 23.9 milliseconds to 130.7 ± 10.0 and 130.1 ± 10.5 milliseconds, respectively (p = 0.01); this was followed by an offset of 40 milliseconds (decreasing QRS duration to 130.1 ± 12.2 milliseconds; p = 0.08). (4) Conclusions: The herein presented NICE-CRT study supports the current recommendation to program an offset of 50 milliseconds as default in patients with left bundle branch block and preserved atrioventricular conduction after implantation of a CRT device capable of SyncAV® optimization. Alternatively, offset programming of 30 milliseconds may also be applied as default programming. In patients with no or poor CRT response, additional efforts should be spent to individualize best offset programming with electrocardiographic optimization techniques.

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.

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.

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.

Cardiac exercise imaging using a 3-tesla magnetic resonance-conditional pedal ergometer: Preliminary results in healthy volunteers and patients with known or suspected coronary artery disease.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR METHODS: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. RESULTS: Median subjective image quality of real-time cine at rest was 1 (interquartile range [IQR] 1-2) and 2 (IQR 2-2.5) for post-exercise real-time cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62-73] to 111 [104-143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m2, respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution postexercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. CONCLUSIONS: Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

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.