Stable patients with suspected myocardial ischemia: comparison of machine-learning computed tomography-based fractional flow reserve and stress perfusion cardiovascular magnetic resonance imaging to detect myocardial ischemia.

BACKGROUND: Machine-Learning Computed Tomography-Based Fractional Flow Reserve (CT-FFRML) is a novel tool for the assessment of hemodynamic relevance of coronary artery stenoses. We examined the diagnostic performance of CT-FFRML compared to stress perfusion cardiovascular magnetic resonance (CMR) and tested if there is an additional value of CT-FFRML over coronary computed tomography angiography (cCTA). METHODS: Our retrospective analysis included 269 vessels in 141 patients (mean age 67 ± 9 years, 78% males) who underwent clinically indicated cCTA and subsequent stress perfusion CMR within a period of 2 months. CT-FFRML values were calculated from standard cCTA. RESULTS: CT-FFRML revealed no hemodynamic significance in 79% of the patients having ≥ 50% stenosis in cCTA. Chi2 values for the statistical relationship between CT-FFRML and stress perfusion CMR was significant (p < 0.0001). CT-FFRML and cCTA (≥ 70% stenosis) provided a per patient sensitivity of 88% (95%CI 64-99%) and 59% (95%CI 33-82%); specificity of 90% (95%CI 84-95%) and 85% (95%CI 78-91%); positive predictive value of 56% (95%CI 42-69%) and 36% (95%CI 24-50%); negative predictive value of 98% (95%CI 94-100%) and 94% (95%CI 90-96%); accuracy of 90% (95%CI 84-94%) and 82% (95%CI 75-88%) when compared to stress perfusion CMR. The accuracy of cCTA (≥ 50% stenosis) was 19% (95%CI 13-27%). The AUCs were 0.89 for CT-FFRML and 0.74 for cCTA (≥ 70% stenosis) and therefore significantly different (p < 0.05). CONCLUSION: CT-FFRML compared to stress perfusion CMR as the reference standard shows high diagnostic power in the identification of patients with hemodynamically significant coronary artery stenosis. This could support the role of cCTA as gatekeeper for further downstream testing and may reduce the number of patients undergoing unnecessary invasive workup.

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.

Prognostic value of novel imaging parameters derived from standard cardiovascular magnetic resonance in high risk patients with systemic light chain amyloidosis.

BACKGROUND: The differentiated assessment of functional parameters besides morphological changes is essential for the evaluation of prognosis in systemic immunoglobulin light chain (AL) amyloidosis. METHODS: Seventy-four subjects with AL amyloidosis and presence of late gadolinium enhancement (LGE) pattern typical for cardiac amyloidosis were analyzed. Long axis strain (LAS) and myocardial contraction fraction (MCF), as well as morphological and functional markers, were measured. The primary endpoint was death, while death and heart transplantation served as a composite secondary endpoint. RESULTS: After a median follow-up of 41 months, 29 out of 74 patients died and 10 received a heart transplant. Left ventricular (LV) functional parameters were reduced in patients, who met the composite endpoint (LV ejection fraction 51% vs. 61%, LAS - 6.9% vs - 10%, GLS - 12% vs - 15% and MCF 42% vs. 69%; p <  0.001 for all). In unadjusted univariate analysis, LAS (HR = 1.05, p <  0.001) and MCF (HR = 0.96, p <  0.001) were associated with reduced transplant-free survival. Kaplan-Meier analyses showed a significantly lower event-free survival in patients with reduced MCF. MCF and LAS performed best to identify high risk patients for secondary endpoint (Log-rank test p <  0.001) in a combined model. Using sequential Cox regression analysis, the addition of LAS and MCF to LV ejection fraction led to a significant increase in the predictive power of the model (χ2 (df = 1) = 28.2, p <  0.001). CONCLUSIONS: LAS and MCF as routinely available and robust CMR-derived parameters predict outcome in LGE positive AL amyloidosis. Patients with impaired LV function in combination with reduced LAS and MCF are at the highest risk for death and heart transplantation.

Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

The prognostic value of right ventricular long axis strain in non-ischaemic dilated cardiomyopathies using standard cardiac magnetic resonance imaging.

OBJECTIVE: To investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM). METHODS: In 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences. RESULTS: The primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below -10% (log-rank, p < 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (>45%, n = 213) reduced RV-LAS was still associated with poor outcome. CONCLUSION: Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters. KEY POINTS: • Impaired right ventricular longitudinal function (RV-LAS) is associated with poorer cardiac outcomes. • Poor outcome is associated with decreased RV-LAS even in patients with RVEF >45%. • Addition of RV-LAS to known risk factors enhances the power prognostic information.

Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

BACKGROUND: To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. METHODS: Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. RESULTS: We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ2 = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ2 = 6.2, p = 0.01). CONCLUSION: In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling.

In preclinical studies, endothelin receptor A (ETA) antagonists (ETAi) attenuated the progression of heart failure (HF). However, clinical HF trials failed to demonstrate beneficial effects of ETAi. These conflicting data may be explained by the possibility that established HF drugs such as adrenergic receptor blockers interfered with the mechanism of ETAi action in clinical trials. Here we report that mice lacking ETA only in sympathetic neurons (SN-KO) showed less adverse structural remodeling and cardiac dysfunction in response to pathological pressure overload induced by transverse aortic constriction (TAC). In contrast, mice lacking ETA only in cardiomyocytes (CM-KO) were not protected. TAC led to a disturbed sympathetic nerve function as measured by cardiac norepinephrine (NE) tissue levels and [(124)I]-metaiodobenzylguanidine-PET, which was prevented in SN-KO. In a rat model of HF, ETAi improved cardiac and sympathetic nerve function. In cocultures of cardiomyocytes (CMs) and sympathetic neurons (SNs), endothelin-1 (ET1) led to a massive NE release and exaggerated CM hypertrophy compared with CM monocultures. ETA-deficient CMs gained a hypertrophic response through wild-type SNs, but ETA-deficient SNs failed to mediate exaggerated CM hypertrophy. Furthermore, ET1 mediated its effects indirectly via NE in CM-SN cocultures through adrenergic receptors and histone deacetylases, resulting in activation of the prohypertrophic transcription factor myocyte enhancer factor 2. In conclusion, sympathetic ETA amplifies ET1 effects on CMs through adrenergic signaling pathways. Thus, antiadrenergic therapies may blunt potentially beneficial effects of ETAi. Taken together, this may indicate that patients with ß blocker intolerance or disturbed sympathetic nerve function could be evaluated for a potential benefit from ETAi.

Quantification of myocardial deformation in children by cardiovascular magnetic resonance feature tracking: determination of reference values for left ventricular strain and strain rate.

BACKGROUND: The objective assessment of global and regional cardiac function in children has shown to be clinically relevant but is challenging to conduct. Cardiovascular magnetic resonance (CMR) has emerged as a valuable diagnostic modality especially in patients with cardiomyopathy or congenital heart disease. However, data on the normal cardiac deformation in children assessed by CMR is lacking at present. Thus, the aim of this study was to provide reference values for cardiac strain and strain rate in children and adolescents derived from CMR feature tracking (FT) measurements. METHODS: In this binational study, eighty children and adolescents (age 0.4-18.0 years, 41 male, 39 female) free from cardiac diseases from two centers underwent CMR in 1.5 T whole-body scanners in supine position. Global peak radial, circumferential and longitudinal systolic strains as well as the corresponding early peak diastolic strain rates were assessed applying FT on short axis as well as 3- and 4-chamber views of standard cine steady-state free precession images. RESULTS: The difference between genders yielded no significance for all assessed strains. Yet, all strains showed a significant parabolic relation to age and an even stronger one to body surface area (BSA). Therefore, BSA-specific reference values were determined using a polynomial regression model. The apical cardiac segments featured significant higher peak circumferential but lower peak radial systolic strains than the midventricular and basal segments (all p < 0.001). CONCLUSIONS: The assessment of cardiac deformation by CMR-FT is feasible in children. This is the first CMR study providing specific reference values for FT-derived strain and strain rate in the pediatric age range.

Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

BACKGROUND: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. METHODS AND RESULTS: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > -5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p < 0.05), presence of LGE (HR: 2.51, p < 0.05) and LAS (HR: 1.28, p < 0.05) were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > -10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. CONCLUSION: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters.

Combined Assessment of High-Sensitivity Troponin T and Noninvasive Coronary Plaque Composition for the Prediction of Cardiac Outcomes.

PURPOSE: To determine the risk-stratification ability of plaque volume and composition assessment with cardiac computed tomographic (CT) angiography and high-sensitivity troponin T (hsTnT) in patients at intermediate risk for coronary artery disease (CAD). MATERIALS AND METHODS: The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients gave written informed consent. Five hundred twenty-one consecutive patients (mean age ± standard deviation, 62 years ± 10; 256 men and 265 women) were included in this prospective, observational, longitudinal, single-center study. Quantitative cardiac CT angiography analysis was performed in all patients (for 7690 coronary segments), whereas biomarkers (hsTnT and high-sensitivity C-reactive protein) were available in 408 patients (78%). To evaluate the incremental value of cardiac CT angiography and hsTnT for the prediction of cardiovascular events, multivariate Cox regression and integrated discrimination improvement analysis were applied. RESULTS: In 521 patients, 13 hard cardiac events occurred during a mean follow-up period of 2.3 years ± 1.1 (median, 2.4 years; range, 0.5-4.5 years), while 23 patients underwent late coronary revascularization. The Duke clinical score was 51% ± 30, indicating intermediate risk. The presence of no plaques or purely calcified versus noncalcified plaques, plaque volume according to tertiles, and increased hsTnT (≥14 pg/mL) was independently associated with hard cardiac events (hazard ratio [HR] = 26.08, 95% confidence interval [CI]: 2.78, 244.99; HR = 12.14, 95% CI: 1.87, 78.74; and HR = 10.31, 95% CI: 2.72, 39.0, respectively; P < .01 for all). Patients with increased hsTnT and plaque burden (n = 53) showed the highest incidence for hard cardiac events (annual rate, 12.7%), followed by those with either increased hsTnT or plaque burden (n = 145; annual rate = 0.44%, P < .03), while those with lower hsTnT and plaque burden exhibited excellent outcomes and no hard event during the follow-up duration (n = 210; annual rate = 0%, P < .001). CONCLUSION: Use of hsTnT as a marker of myocardial microinjury and cardiac CT angiography as a marker of the total atherosclerotic burden improves the prediction of cardiac outcome in patients with presumably stable CAD and may aid in personalized risk stratification in patients at intermediate risk.

Biomarker changes after strenuous exercise can mimic pulmonary embolism and cardiac injury--a metaanalysis of 45 studies.

BACKGROUND: Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment. METHODS: We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included. RESULTS: Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%-64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2-46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction. CONCLUSIONS: Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.

Age- and gender-related normal left ventricular deformation assessed by cardiovascular magnetic resonance feature tracking.

BACKGROUND: Assessment of left (LV) ventricular function is one of the most important tasks of cardiovascular magnetic resonance (CMR). Impairment of LV deformation is a strong predictor of cardiovascular outcome in various cardiac diseases like ischemic heart disease or cardiomyopathies. The aim of the study was to provide reference values for myocardial deformation derived from the CMR feature tracking imaging (FTI) algorithm in a reference population of healthy volunteers. METHODS: FTI was applied to standard short axis and 2-, 3- and 4-chamber views of vector-ECG gated CMR cine SSFP sequences of 150 strictly selected healthy volunteers (75 male/female) of three age tertiles (mean age 45.8 yrs). Global peak and mean radial, circumferential and longitudinal endo- and myocardial systolic strain values as well as early diastolic strain rates were measured using FTI within a standard protocol on a 1.5T whole body MR scanner. RESULTS: Global peak systolic values were 36.3 ± 8.7% for radial, -27.2 ± 4.0% for endocardial circumferential, -21.3 ± 3.3% for myocardial circumferential, -23.4 ± 3.4% for endocardial longitudinal and -21.6 ± 3.2% for myocardial longitudinal strain. Global peak values were -2.1 ± 0.5 s(-1) for radial, 2.1 ± 0.6 s(-1) for circumferential endocardial, 1.7 ± 0.5 s(-1) for circumferential myocardial, 1.8 (1.5-2.2) s(-1) for longitudinal endocardial, 1.6 (1.4-2.0) s(-1) for longitudinal myocardial early diastolic strain rates. Men showed a higher radial strain than women whereas the circumferential and longitudinal strains were lower resulting in less negative values. Circumferential and longitudinal strain rates were significantly higher in female subjects. Radial strain increased significantly with age whereas the diastolic function measured by the radial, circumferential and longitudinal strain rates showed a decrease. The coefficients of variation determined in ten further subjects, who underwent two CMR examinations within 12 days, were -4.8% for circumferential and -4.5% for longitudinal endocardial mean strains. CONCLUSIONS: Myocardial deformation analysis using FTI is a novel technique and robust when applied to standard cine CMR images providing the possibility of a reliable, objective quantification of global LV deformation. Since strain values and strain rates differed partly between genders as well as between age groups, the application of specific reference values as provided by this study is recommendable.

Fast assessment of long axis strain with standard cardiovascular magnetic resonance: a validation study of a novel parameter with reference values.

BACKGROUND: Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR. METHODS: 40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula. RESULTS: LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches. LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI (67 ± 8 s vs. 180 ± 14 s, p < 0.0001). Additionally, LAS-epi/mid performed significantly better than MAPSE (Delta AUC = 0.09; p < 0.005) and the ejection fraction (Delta AUC = 0.11; p = 0.0002). Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was -17.1 ± 2.3 %. Mean values for men were significantly lower compared to women (-16.5 ± 2.2 vs. -17.9 ± 2.1 %; p < 0.0001), while LAS decreased with age. CONCLUSIONS: LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain.

Aldosterone augments Na+-induced reduction of cardiac norepinephrine reuptake.

Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake. To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 µg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake.

Effects of high- versus low-intensity lipid-lowering treatment in patients undergoing serial coronary computed tomography angiography: results of the multi-center LOCATE study.

AIM: To evaluate the effects of lipid-lowering medications of different intensities on total, calcified, and non-calcified plaque volumes in patients undergoing serial cardiac computed tomography angiography (CCTA). METHODS: Individuals with chronic coronary syndromes from 11 centers were included in a retrospective registry. Total, calcified, and non-calcified plaque volumes were quantified and the relative difference in plaque volumes between baseline and follow-up CCTA was calculated. The intensity of lipid-lowering treatment was designated as low, moderate, or high, based on current recommendations. RESULTS: Of 216 patients (mean age 63.1 ± 9.7 years), undergoing serial CCTA (median timespan = 824.5 [IQR = 463.0-1323.0] days), 89 (41.2%) received no or low-intensity lipid-lowering medications, and 80 (37.0%) and 47 (21.8%) moderate- and high-intensity lipid-lowering agents, respectively. Progression of total and non-calcified plaque was attenuated in patients on moderate-/high- versus those on no/low-intensity treatment and arrested in patients treated with high-intensity statins or PCSK9 inhibitors (p < 0.001). Halted increase of non-calcified plaque was associated with LDL-cholesterol reduction (p < 0.001), whereas calcified plaque mass and Agatston score increased irrespective of the lipid-lowering treatment (p = NS). The intensity of lipid-lowering therapy robustly predicted attenuation of non-calcified plaque progression as a function of the time duration between the two CCTA scans, and this was independent of age and cardiovascular risk factors (HR = 3.83, 95% CI = 1.81-8.05, p < 0.001). CONCLUSION: The LOCATE multi-center observational study shows that progression of non-calcified plaques, which have been previously described as precursors of acute coronary syndromes, can be attenuated with moderate-intensity, and arrested with high-intensity lipid-lowering therapy. GERMAN CLINICAL TRIALS REGISTER: DRKS00031954.

Comparison of Two Contemporary Quantitative Atherosclerotic Plaque Assessment Tools for Coronary Computed Tomography Angiography: Single-Center Analysis and Multi-Center Patient Cohort Validation.

BACKGROUND: Coronary computed tomography angiography (CCTA) provides non-invasive quantitative assessments of plaque burden and composition. The quantitative assessment of plaque components requires the use of analysis software that provides reproducible semi-automated plaque detection and analysis. However, commercially available plaque analysis software can vary widely in the degree of automation, resulting in differences in terms of reproducibility and time spent. AIM: To compare the reproducibility and time spent of two CCTA analysis software tools using different algorithms for the quantitative assessment of coronary plaque volumes and composition in two independent patient cohorts. METHODS: The study population included 100 patients from two different cohorts: 50 patients from a single-center (Siemens Healthineers, SOMATOM Force (DSCT)) and another 50 patients from a multi-center study (5 different > 64 slice CT scanner types). Quantitative measurements of total calcified and non-calcified plaque volume of the right coronary artery (RCA), left anterior descending (LAD), and left circumflex coronary artery (LCX) were performed on a total of 300 coronaries by two independent readers, using two different CCTA analysis software tools (Tool #1: Siemens Healthineers, syngo.via Frontier CT Coronary Plaque Analysis and Tool #2: Siemens Healthineers, successor CT Coronary Plaque Analysis prototype). In addition, the total time spent for the analysis was recorded with both programs. RESULTS: The patients in cohorts 1 and 2 were 62.8 ± 10.2 and 70.9 ± 11.7 years old, respectively, 10 (20.0%) and 35 (70.0%) were female and 34 (68.0%) and 20 (40.0%), respectively, had hyperlipidemia. In Cohort #1, the inter- and intra-observer variabilities for the assessment of plaque volumes per patient for Tool #1 versus Tool #2 were 22.8%, 22.0%, and 26.0% versus 2.3%, 3.9%, and 2.5% and 19.7%, 21.4%, and 22.1% versus 0.2%, 0.1%, and 0.3%, respectively, for total, noncalcified, and calcified lesions (p < 0.001 for all between Tools #1 and 2 both for inter- and intra-observer). The inter- and intra-observer variabilities using Tool #2 remained low at 2.9%, 2.7%, and 3.0% and 3.8%, 3.7%, and 4.0%, respectively, for total, non-calcified, and calcified lesions in Cohort #2. For each dataset, the median processing time was higher for Tool #1 versus Tool #2 (459.5 s IQR = 348.0-627.0 versus 208.5 s; IQR = 198.0-216.0) (p < 0.001). CONCLUSION: The plaque analysis Tool #2 (CT-guided PCI) encompassing a higher degree of automated support required less manual editing, was more time-efficient, and showed a higher intra- and inter-observer reproducibility for the quantitative assessment of plaque volumes both in a representative single-center and in a multi-center validation cohort.

Simultaneous assessment of heart and lungs with gated high-pitch ultra-low dose chest CT using artificial intelligence-based calcium scoring.

Purpose: The combined testing for coronary artery and pulmonary diseases is of clinical interest as risk factors are shared. In this study, a novel ECG-gated tin-filtered ultra-low dose chest CT protocol (GCCT) for integrated heart and lung acquisition and the applicability of artificial intelligence (AI)-based coronary artery calcium scoring were assessed. Methods: In a clinical registry of 10481 patients undergoing heart and lung CT, GCCT was applied in 44 patients on a dual-source CT. Coronary calcium scans (CCS) with 120 kVp, 100 kVp, and tin-filtered 100 kVp (Sn100) of controls, matched with regard to age, sex, and body-mass index, were retrieved from the registry (ntotal=176, 66.5 (59.4-74.0) years, 52 men). Automatic tube current modulation was used in all scans. In 20 patients undergoing GCCT and Sn100 CCS, Agatston scores were measured both semi-automatically by experts and by AI, and classified into six groups (0, <10, <100, <400, <1000, ≥1000). Results: Effective dose decreased significantly from 120 kVp CCS (0.50 (0.41-0.61) mSv) to 100 kVp CCS (0.34 (0.26-0.37) mSv) to Sn100 CCS (0.14 (0.11-0.17) mSv). GCCT showed higher values (0.28 (0.21-0.32) mSv) than Sn100 CCS but lower than 120 kVp and 100 kVp CCS (all p < 0.05) despite greater scan length. Agatston scores correlated strongly between GCCT and Sn100 CCS in semi-automatic and AI-based measurements (both ρ = 0.98, p < 0.001) resulting in high agreement in Agatston score classification (κ = 0.97, 95% CI 0.92-1.00; κ = 0.89, 95% CI 0.79-0.99). Regarding chest findings, further diagnostic steps were recommended in 28 patients. Conclusions: GCCT allows for reliable coronary artery disease and lung cancer screening with ultra-low radiation exposure. GCCT-derived Agatston score shows excellent agreement with standard CCS, resulting in equivalent risk stratification.

How scan parameter choice affects deep learning-based coronary artery disease assessment from computed tomography.

Recently, algorithms capable of assessing the severity of Coronary Artery Disease (CAD) in form of the Coronary Artery Disease-Reporting and Data System (CAD-RADS) grade from Coronary Computed Tomography Angiography (CCTA) scans using Deep Learning (DL) were proposed. Before considering to apply these algorithms in clinical practice, their robustness regarding different commonly used Computed Tomography (CT)-specific image formation parameters-including denoising strength, slab combination, and reconstruction kernel-needs to be evaluated. For this study, we reconstructed a data set of 500 patient CCTA scans under seven image formation parameter configurations. We select one default configuration and evaluate how varying individual parameters impacts the performance and stability of a typical algorithm for automated CAD assessment from CCTA. This algorithm consists of multiple preprocessing and a DL prediction step. We evaluate the influence of the parameter changes on the entire pipeline and additionally on only the DL step by propagating the centerline extraction results of the default configuration to all others. We consider the standard deviation of the CAD severity prediction grade difference between the default and variation configurations to assess the stability w.r.t. parameter changes. For the full pipeline we observe slight instability (± 0.226 CAD-RADS) for all variations. Predictions are more stable with centerlines propagated from the default to the variation configurations (± 0.122 CAD-RADS), especially for differing denoising strengths (± 0.046 CAD-RADS). However, stacking slabs with sharp boundaries instead of mixing slabs in overlapping regions (called true stack ± 0.313 CAD-RADS) and increasing the sharpness of the reconstruction kernel (± 0.150 CAD-RADS) leads to unstable predictions. Regarding the clinically relevant tasks of excluding CAD (called rule-out; AUC default 0.957, min 0.937) and excluding obstructive CAD (called hold-out; AUC default 0.971, min 0.964) the performance remains on a high level for all variations. Concluding, an influence of reconstruction parameters on the predictions is observed. Especially, scans reconstructed with the true stack parameter need to be treated with caution when using a DL-based method. Also, reconstruction kernels which are underrepresented in the training data increase the prediction uncertainty.

Human AI Teaming for Coronary CT Angiography Assessment: Impact on Imaging Workflow and Diagnostic Accuracy.

As the number of coronary computed tomography angiography (CTA) examinations is expected to increase, technologies to optimize the imaging workflow are of great interest. The aim of this study was to investigate the potential of artificial intelligence (AI) to improve clinical workflow and diagnostic accuracy in high-volume cardiac imaging centers. A total of 120 patients (79 men; 62.4 (55.0-72.7) years; 26.7 (24.9-30.3) kg/m2) undergoing coronary CTA were randomly assigned to a standard or an AI-based (human AI) coronary analysis group. Severity of coronary artery disease was graded according to CAD-RADS. Initial reports were reviewed and changes were classified. Both groups were similar with regard to age, sex, body mass index, heart rate, Agatston score, and CAD-RADS. The time for coronary CTA assessment (142.5 (106.5-215.0) s vs. 195.0 (146.0-265.5) s; p < 0.002) and the total reporting time (274.0 (208.0-377.0) s vs. 350 (264.0-445.5) s; p < 0.02) were lower in the human AI than in the standard group. The number of cases with no, minor, or CAD-RADS relevant changes did not differ significantly between groups (52, 7, 1 vs. 50, 8, 2; p = 0.80). AI-based analysis significantly improves clinical workflow, even in a specialized high-volume setting, by reducing CTA analysis and overall reporting time without compromising diagnostic accuracy.

Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy.

The attenuation of adverse myocardial remodeling and pathological left ventricular (LV) hypertrophy is one of the hallmarks for improving the prognosis after myocardial infarction (MI). The protein kinase Akt plays a central role in regulating cardiac hypertrophy, but the in vivo effects of chronic pharmacological inhibition of Akt are unknown. We investigated the effect of chronic Akt blockade with deguelin on the development of pathological [MI and aortic banding (AB)] and physiological (controlled treadmill running) hypertrophy. Primary cardiomyocyte cultures were incubated with 10 µmol deguelin for 48 h, and Wistar rats were treated orally with deguelin (4.0 mg·kg(-1)·day(-1)) for 4 wk starting 1 day after the induction of MI or AB. Exercise-trained animals received deguelin for 4 wk during the training period. In vitro, we observed reduced phosphorylation of Akt and glycogen synthase kinase (GSK)-3ß after an incubation with deguelin, whereas MAPK signaling was not significantly affected. In vivo, treatment with deguelin led to attenuated phosphorylation of Akt and GSK-3ß 4 wk after MI. These animals showed significantly increased heart weights and impaired LV function with increased end-diastolic diameters (12.0 ± 0.3 vs. 11.1 ± 0.3 mm, P < 0.05), end-diastolic volumes (439 ± 8 vs. 388 ± 18 µl, P < 0.05), and cardiomyocyte sizes (+20%, P < 0.05) compared with MI animals receiving vehicle treatment. Furthermore, activation of Ca(2+)/calmodulin-dependent kinase II in deguelin-treated MI animals was increased compared with the vehicle-treated group. Four wk after AB, we observed an augmentation of pathological hypertrophy in the deguelin-treated group with a significant increase in heart weights and cardiomyocyte sizes (>20%, P < 0.05). In contrast, the development of physiological hypertrophy was inhibited by deguelin treatment in exercise-trained animals. In conclusion, chronic Akt blockade with deguelin aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy.