Layer-specific fast strain-encoded cardiac magnetic resonance imaging aids in the identification and discrimination of acute myocardial injury: a prospective proof-of-concept study.

BACKGROUND: Acute myocardial injury is a common diagnosis in the emergency department and differential diagnoses are numerous. Cardiac magnetic resonance (CMR) strain sequences, such as fast strain ENCoded (fSENC), are early predictors of myocardial function loss. This study assessed the potential diagnostic and prognostic benefits of a layer-specific approach. METHODS: For this prospective study, patients in the emergency department fulfilling rule-in criteria for non-ST-elevation myocardial infarction (NSTEMI) received an ultra-fast fSENC CMR. Volunteers without cardiac diseases (controls) were recruited for comparison. Measurements were performed in a single heartbeat acquisition to measure global longitudinal strain (GLS) and segmental longitudinal strain and dysfunctional segments. The GLS was measured in two layers and a difference (GLSdifference = GLSepicardial - GLSendocardial) was calculated. The performance of those strain features was compared to standard care (physical examination, cardiac biomarkers, electrocardiogram). According to the final diagnosis after discharge, patients were divided into groups and followed up for 2 years. RESULTS: A total of 114 participants, including 50 controls, were included. The 64 patients (51 male) were divided into a NSTEMI (25), myocarditis (16), and other myocardial injury group (23). GLS served as a potent predictor of myocardial injury (area under the curve (AUC) 91.8%). The GLSdifference provided an excellent diagnostic performance to identify a NSTEMI (AUC 83.2%), further improved by including dysfunctional segments (AUC 87.5%, p = 0.01). An optimal test was achieved by adding fSENC to standard care (AUC 95.5%, sensitivity 96.0%, specificity 86.5%, p = 0.03). No death occurred in 2 years for patients with normal GLS and ≤5 dysfunctional segments, while three patients died that showed abnormal GLS or >5 dysfunctional segments. CONCLUSIONS: Layer-specific strain is a potential new marker with high diagnostic performance in the identification and differentiation of acute myocardial injuries.

Predictors of persistent symptoms after mRNA SARS-CoV-2 vaccine-related myocarditis (myovacc registry).

Aims: Epidemiological surveillance has raised safety concerns for mRNA SARS-CoV-2-vaccination-related myocarditis. We aimed to analyze epidemiological, clinical and imaging findings associated with clinical outcomes in these patients in an international multi-center registry (NCT05268458). Methods and results: Patients with clinical and CMR diagnosis of acute myocarditis within 30 days after mRNA SARS-CoV-2-vaccination were included from five centers in Canada and Germany between 05/21 and 01/22. Clinical follow-up on persistent symptoms was collected. We enrolled 59 patients (80% males, mean age 29 years) with CMR-derived mild myocarditis (hs-Troponin-T 552 [249-1,193] ng/L, CRP 28 [13-51] mg/L; LVEF 57 ± 7%, LGE 3 [2-5] segments). Most common symptoms at baseline were chest pain (92%) and dyspnea (37%). Follow-up data from 50 patients showed overall symptomatic burden improvement. However, 12/50 patients (24%, 75% females, mean age 37 years) reported persisting symptoms (median interval 228 days) of chest pain (n = 8/12, 67%), dyspnea (n = 7/12, 58%), with increasing occurrence of fatigue (n = 5/12, 42%) and palpitations (n = 2/12, 17%). These patients had initial lower CRP, lower cardiac involvement in CMR, and fewer ECG changes. Significant predictors of persisting symptoms were female sex and dyspnea at initial presentation. Initial severity of myocarditis was not associated with persisting complaints. Conclusion: A relevant proportion of patients with mRNA SARS-CoV-2-vaccination-related myocarditis report persisting complaints. While young males are usually affected, patients with persisting symptoms were predominantly females and older. The severity of the initial cardiac involvement not predicting these symptoms may suggest an extracardiac origin.

Safety of Stress Cardiac Magnetic Resonance in Patients With Moderate to Severe Aortic Valve Stenosis.

BACKGROUND: Dobutamine and adenosine stress cardiac magnetic resonance (CMR) imaging is relatively contraindicated in patients with moderate to severe aortic valve stenosis (AS). We aimed to determine the safety of dobutamine and adenosine stress CMR in patients with moderate to severe AS. METHODS: In this retrospective study patients with AS who underwent either dobutamine or adenosine stress CMR for exclusion of obstructive coronary artery disease were enrolled. We recorded clinical data, CMR and echocardiography findings, and complications as well as minor symptoms. Patients with AS were compared to matched individuals without AS. RESULTS: A total of 187 patients with AS were identified and compared to age-, gender- and body mass index-matched 187 patients without AS. No severe complications were reported in the study nor the control group. The reported frequency of non-severe complications and minor symptoms were similar between the study and the control groups. Nineteen patients with AS experienced non-severe complications or minor symptoms during dobutamine stress CMR compared to eighteen patients without AS (p = 0.855). One patient with AS and two patients without AS undergoing adenosine stress CMR experienced minor symptoms (p = 0.562). Four examinations were aborted because of chest pain, paroxysmal atrial fibrillation and third-degree atrioventricular block. Inducible ischaemia, prior coronary artery bypass grafting, prior stroke and age were associated with a higher incidence of complications and minor symptoms. CONCLUSIONS: Moderate to severe AS was not associated with complications during CMR stress test. The incidence of non-severe complications and minor symptoms was greater with dobutamine.

Case report: Case series of isolated acute pericarditis after SARS-CoV-2 vaccinations.

During the worldwide ongoing immunization campaign against SARS-CoV-2, growing data on very rare but potentially harmful side effects of such vaccines arise since approval trials have not been adequately powered to detect those events. Besides the already reported vaccine-related myocarditis, which primarily occurs in young male individuals, our attention was recently drawn to a series of older male and female patients, who were referred to our institutions with isolated acute pericarditis without myocardial damage, shortly after SARS-CoV-2 vaccination. We describe a series of five adult patients presenting with chest pain, shortness of breath and isolated pericarditis with and without pericardial effusion after SARS-CoV-2 vaccination. All patients underwent echocardiography and cardiac magnetic resonance, and the corresponding findings, including late gadolinium enhancement (LGE) and T1 and T2 mapping are reported herein. To our knowledge, such cases have not been systematically reported in the current literature so far.

A head-to-head comparison of fast-SENC and feature tracking to LV long axis strain for assessment of myocardial deformation in chest pain patients.

BACKGROUND: Myocardial strain imaging has gained importance in cardiac magnetic resonance (CMR) imaging in recent years as an even more sensitive marker of early left ventricular dysfunction than left-ventricular ejection fraction (LVEF). fSENC (fast strain encoded imaging) and FT (feature tracking) both allow for reproducible assessment of myocardial strain. However, left-ventricular long axis strain (LVLAS) might enable an equally sensitive measurement of myocardial deformation as global longitudinal or circumferential strain in a more rapid and simple fashion. METHODS: In this study we compared the diagnostic performance of fSENC, FT and LVLAS for identification of cardiac pathology (ACS, cardiac-non-ACS) in patients presenting with chest pain (initial hscTnT 5-52 ng/l). Patients were prospectively recruited from the chest pain unit in Heidelberg. The CMR scan was performed within 1 h after patient presentation. Analysis of LVLAS was compared to the GLS and GCS as measured by fSENC and FT. RESULTS: In total 40 patients were recruited (ACS n = 6, cardiac-non-ACS n = 6, non-cardiac n = 28). LVLAS was comparable to fSENC for differentiation between healthy myocardium and myocardial dysfunction (GLS-fSENC AUC: 0.882; GCS-fSENC AUC: 0.899; LVLAS AUC: 0.771; GLS-FT AUC: 0.740; GCS-FT: 0.688), while FT-derived strain did not allow for differentiation between ACS and non-cardiac patients. There was significant variability between the three techniques. Intra- and inter-observer variability (OV) was excellent for fSENC and FT, while for LVLAS the agreement was lower and levels of variability higher (intra-OV: Pearson > 0.7, ICC > 0.8; inter-OV: Pearson > 0.65, ICC > 0.8; CoV > 25%). CONCLUSIONS: While reproducibility was excellent for both FT and fSENC, it was only fSENC and the LVLAS which allowed for significant identification of myocardial dysfunction, even before LVEF, and therefore might be used as rapid supporting parameters for assessment of left-ventricular function.

Hypverventilation strain CMR imaging in patients with acute chest pain.

In patients with suspected acute coronary syndrome high-sensitivity cardiac tropnonin T is used for rapid patient triage. Some acute coronary syndrome patients assigned to the observe zone based on high-sensitivity cardiac troponin T after 1 h require further diagnostic testing. Fast-strain encoded CMR imaging with breathing maneuvers may accelerate diagnostic work-up and identify patients suffering from acute coronary syndrome. Patients presenting with acute chest pain (high-sensitivity cardiac troponin T level 5-52 ng/L) were prospectively enrolled (consecutive sampling, time of recruitment: 09/18-06/19). Fast-strain-encoded imaging was performed within the 1-h timeframe (0 h/1 h algorithm) prior to 2nd high-sensitivity troponin T lab results. Images were acquired at rest as well as after 1-min of hyperventilation followed by a short breath-hold. In 108 patients (59 male; mean age: 57 ± 17y) the mean study time was 17 ± 3 min. An abnormal strain response after the breathing maneuver (persistent/increased/new onset of increased strain rates) correctly identified all 17 patients with a high-sensitivity troponin T dynamic (0 h/1 h algorithm) and explanatory significant coronary lesions, while in 86 patients without serologic or angiographic evidence for severe coronary artery disease the strain response was normal (sensitivity 100%, specificity 94.5%; 5 false positive results). The number of dysfunctional segments (strain > - 10%) proved to be a quantifiable marker for identifying patients with acute coronary syndrome. In patients with suspected acute coronary syndrome and inconclusive initial high-sensitivity troponin T, fast-strain-encoded imaging with a breathing maneuver may safely and rapidly identify patients with acute coronary syndrome, without the need for vasodilators, stress, or contrast agents.

Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure.

PURPOSE: Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx). METHODS: A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg-1·day-1 HA over a 4-week period. RESULTS: 5/6 Nx per se resulted in adverse myocardial remodeling with aggravated cardiac function and associated cardiac overload as the most obvious alteration (-23% ejection fraction, P < 0.0001), as well as increased myocardial fibrosis (+80%, P = 0.0005) compared to placebo treated sham animals. HA treatment of 5/6 Nx rats has led to an improvement of ejection fraction (+24%, P = 0.0003) and fractional shortening (+21%, P = 0.0126), as well as a decrease of collagen deposition (-32%, P = 0.0041), left ventricular weight (-14%, P = 0.0468), and myocyte cross-sectional area (-12%, P < 0.0001). These changes were accompanied by a downregulation of atrial natriuretic factor (-65% P < 0.0001) and collagen type V alpha 1 chain (-44%, P = 0.0006). Sham animals revealed no significant changes in cardiac function, myocardial fibrosis, or any of the aforementioned molecular changes after drug treatment. CONCLUSION: Dietary HA supplementation appears to have the potential of preventing cardiac remodeling and improving heart function in the setting of chronic kidney disease. Our findings shed new light on HA as a possible new therapeutic agent for patients at high cardiovascular risk.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test.

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations. Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion. Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: -19.4 ± 1.9%, GLSDHE: -20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= -19.5 ± 2.3%, GLSDob= -19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001). Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Myocardial mechanics in dilated cardiomyopathy: prognostic value of left ventricular torsion and strain.

BACKGROUND: Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). METHODS: CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. RESULTS: GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p < 0.001). The primary endpoint occurred in 59 (18.7%) patients [median follow-up 4.2 (2.0-5.6) years]. In the univariate analyses all strain parameters showed a significant prognostic value (p < 0.05). In the multivariate model, LV strain parameters, particularly GLS provided an incremental prognostic value compared to established CMR parameters like LV ejection fraction and late gadolinium enhancement. A scoring model including six categorical variables of standard CMR and strain parameters differentiated further risk subgroups. CONCLUSION: LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

Causes of altered ventricular mechanics in hypertrophic cardiomyopathy: an in-silico study.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or contrast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements. METHODS: We conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart models were evaluated globally and regionally. RESULTS: Hypertrophy of the LV affected the course of strain, strain rate, and wall thickening-the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduction of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA. CONCLUSIONS: This study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of HCM.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Feasibility of fast cardiovascular magnetic resonance strain imaging in patients presenting with acute chest pain.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the current reference standard for the quantitative assessment of ventricular function. Fast Strain-ENCoded (fSENC)-CMR imaging allows for the assessment of myocardial deformation within a single heartbeat. The aim of this pilot study was to identify obstructive coronary artery disease (oCAD) with fSENC-CMR in patients presenting with new onset of chest pain. METHODS AND RESULTS: In 108 patients presenting with acute chest pain, we performed fSENC-CMR after initial clinical assessment in the emergency department. The final clinical diagnosis, for which cardiology-trained physicians used clinical information, serial high-sensitive Troponin T (hscTnT) values and-if necessary-further diagnostic tests, served as the standard of truth. oCAD was defined as flow-limiting CAD as confirmed by coronary angiography with typical angina or hscTnT dynamics. Diagnoses were divided into three groups: 0: non-cardiac, 1: oCAD, 2: cardiac, non-oCAD. The visual analysis of fSENC bull´s eye maps (blinded to final diagnosis) resulted in a sensitivity of 82% and specificity of 87%, as well as a negative predictive value of 96% for identification of oCAD. Both, global circumferential strain (GCS) and global longitudinal strain (GLS) accurately identified oCAD (area under the curve/AUC: GCS 0.867; GLS 0.874; p<0.0001 for both), outperforming ECG, hscTnT dynamics and EF. Furthermore, the fSENC analysis on a segmental basis revealed that the number of segments with impaired strain was significantly associated with the patient´s final diagnosis (p<0.05 for all comparisons). CONCLUSION: In patients with acute chest pain, myocardial strain imaging with fSENC-CMR may serve as a fast and accurate diagnostic tool for ruling out obstructive coronary artery disease.

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block.

BACKGROUND: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. METHODS: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. RESULTS: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. CONCLUSIONS: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. TRIAL REGISTRATION: This study was retrospectively registered.

Hyperventilation/Breath-Hold Maneuver to Detect Myocardial Ischemia by Strain-Encoded CMR: Diagnostic Accuracy of a Needle-Free Stress Protocol.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH). BACKGROUND: Myocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations. METHODS: Patients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference. RESULTS: A total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p < 0.05) and territory level (adenosine-strain: sensitivity 67%, specificity 93%; HVBH-strain: sensitivity 63%, specificity 95% vs. adenosine-perfusion: sensitivity 49%, specificity 96%; p < 0.05). However, these differences in diagnostic accuracy disappear by excluding patients with history of coronary artery bypass graft or previous myocardial infarction. The response of longitudinal strain differs significantly between ischemic and nonischemic segments to adenosine (ΔLSischemic = 0.6 ± 5.4%, ΔLSnonischemic = -0.9 ± 2.7%; p < 0.05) and HVBH (ΔLSischemic = 1.3% ± 3.8%, ΔLSnonischemic = -0.3 ± 1.8%; p = 0.002). Test duration of HVBH-strain (t = 64 ± 2 s) was significantly shorter compared with adenosine-strain (t = 184 ± 59 s; p < 0.0001) and adenosine-perfusion (t = adenosine-perfusion: 172 ± 59 s; p < 0.0001). CONCLUSIONS: HVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.

Estimating cardiac active tension from wall motion-An inverse problem of cardiac biomechanics.

The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics-estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill-posed non-linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE <20% of the maximal tension, the fiber orientation needs to be provided with an accuracy of 10°. Also, variation was added to the deformation data in the range of segmentation accuracy. Here, imposing temporal regularization led to an eightfold decrease in the error down to 12%. Furthermore, non-contracting regions representing myocardial infarct scars were introduced in the left ventricle and could be identified accurately in the inverse solution (sensitivity >0.95). The results obtained with non-matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue.

Gender-specific reference values for high-sensitivity cardiac troponin T and I in well-phenotyped healthy individuals and validity of high-sensitivity assay designation.

OBJECTIVE: To determine gender-specific reference limits of high-sensitivity (hs) cardiac troponins (cTn) and validity of hs assay designation for both genders. METHODS: After screening with a questionnaire, 827 presumably healthy individuals were further selected based on clinical criteria (n = 740), clinical criteria plus cardiac imaging including stress magnetic resonance imaging or stress echocardiography (n = 726), and extended cardio-pulmonary parameters (n = 626). Blood samples were measured with hs-cTnT (Roche Diagnostics) on a cobas e602 analyzer as well as hs-cTnI (Abbott Diagnostics) on an ARCHITECTi2000SR. The impact of health definition, statistical methods, instrument selection and limit of detection (LoD) on overall and gender-specific 99th percentiles was assessed. RESULTS: Median age was 56 years (50.9% female) for the total study cohort. 99th percentiles for females and males ranged between 13.1 and 13.3 ng/L and 16.8-19.9 ng/L for hs-cTnT as well as 10.3-12.5 ng/L and 27.4-29.7 ng/L for hs-cTnI depending on health definition. Utilization of stricter health definition criteria reduced the difference of the gender-specific 99th percentiles between males and females for hs-cTnT to 3.7 ng/L (males 16.8 ng/L, females 13.1 ng/L), whereas the difference rather increased for hs-cTnI to 19.4 ng/L (males 29.7 ng/L, females 10.3 ng/L). Values > LoD could be measured in the majority of males and females using hs-TnT (81.4-83.3% and 96.5-96.9%, respectively). In contrast, values > LoD could not be observed in the majority of females using hs-cTnI (38.4-41.1%). CONCLUSIONS: In a well-phenotyped healthy cohort, reference values for hs-cTnT were slightly higher, whereas hs-cTnI cut-offs were considerably lower than previously observed. Gender differences were more pronounced in hs-cTnI than in hs-cTnT and were further reduced for hs-cTnT by application of stricter health definition criteria. Contrary to hs-cTnI, hs-cTnT fulfilled criteria for hs designation for both genders.

Cardiovascular magnetic resonance of cardiac morphology and function: impact of different strategies of contour drawing and indexing.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the gold standard for the quantitative assessment of cardiac volumes, mass and function. There are, however, various strategies for establishing endocardial borders, the cardiac phase used for measurements and the body dimensions used for indexing these results. The aim of the study was to assess the impact of different strategies on reference values. METHODS AND RESULTS: 362 healthy volunteers (190 men, mean age 51 ± 13 years) underwent a standard CMR protocol. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were measured at end systole and end diastole in SSFP sequences using two methods, one of which included papillary muscles and trabecular tissue in the LV-M ("include" approach), while the other excluded this tissue ("exclude" approach). There was a strong correlation between the results for LV volumes and LV ejection fraction (LV-EF) between the "include" and the "exclude" approach, while the mean values were different: LV-EDV: 149.7 ± 32.5 ml vs 160.5 ± 35.0 ml, p < 0.0001; LV-ESV: 48.7 ± 14.5 ml vs 56.4 ± 16.7 ml, p < 0.0001; LV-EF: 67.7 ± 5.4% vs 65.1 ± 5.6%, p < 0.0001. When comparing end-systolic with end-diastolic data, values for LV-M were significantly higher in end systole irrespective of whether papillary muscles and trabecular tissues were included or not. Furthermore, LV-M missed overweight-induced LV hypertrophy when indexed to body surface area (BSA) instead of height. CONCLUSION: Quantitative assessment of LV volumes and mass with inclusion of papillary muscles and trabeculae to myocardial mass resulted in significantly different values, while indexing to BSA and not height may miss LV hypertrophy in terms of overweight.