Cardiovascular magnetic resonance feature tracking in small animals – a preliminary study on reproducibility and sample size calculation

Background Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel tissue tracking technique developed for noninvasive assessment of myocardial motion and deformation. This preliminary study aimed to evaluate the observer’s reproducibility of CMR-FT in a small animal (mouse) model and define sample size calculation for future trials. Methods Six C57BL/6 J mice were selected from the ongoing experimental mouse model onsite and underwent CMR with a 3 Tesla small animal MRI scanner. Myocardial deformation was analyzed using dedicated software (TomTec, Germany) by two observers. Left ventricular (LV) longitudinal, circumferential and radial strain (EllLAX, EccSAX and ErrSAX) were calculated. To assess intra-observer agreement data analysis was repeated after 4 weeks. The sample size required to detect a relative change in strain was calculated. Results In general, EccSAX and EllLAX demonstrated highest inter-observer reproducibility (ICC 0.79 (0.46–0.91) and 0.73 (0.56–0.83) EccSAX and EllLAX respectively). In contrast, at the intra-observer level EllLAX was more reproducible than EccSAX (ICC 0.83 (0.73–0.90) and 0.74 (0.49–0.87) EllLAX and EccSAX respectively). The reproducibility of ErrSAX was weak at both observer levels. Preliminary sample size calculation showed that a small study sample (e.g. ten animals to detect a relative 10% change in EccSAX) could be sufficient to detect changes if parameter variability is low. Conclusions This pilot study demonstrates good to excellent inter- and intra-observer reproducibility of CMR-FT technique in small animal model. The most reproducible measures are global circumferential and global longitudinal strain, whereas reproducibility of radial strain is weak. Furthermore, sample size calculation demonstrates that a small number of animals could be sufficient for future trials

Assessment of Global Longitudinal and Circumferential Strain Using Computed Tomography Feature Tracking: Intra-Individual Comparison with CMR Feature Tracking and Myocardial Tagging in Patients with Severe Aortic Stenosis

In this study, we used a single commercially available software solution to assess global longitudinal (GLS) and global circumferential strain (GCS) using cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) feature tracking (FT). We compared agreement and reproducibility between these two methods and the reference standard, CMR tagging (TAG). Twenty-seven patients with severe aortic stenosis underwent CMR and cardiac CT examinations. FT analysis was performed using Medis suite version 3.0 (Leiden, The Netherlands) software. Segment (Medviso) software was used for GCS assessment from tagged images. There was a trend towards the underestimation of GLS by CT-FT when compared to CMR-FT (19.4 +/- 5.04 vs. 22.40 +/- 5.69, respectively; p = 0.065). GCS values between TAG, CT-FT, and CMR-FT were similar (p = 0.233). CMR-FT and CT-FT correlated closely for GLS (r = 0.686, p < 0.001) and GCS (r = 0.707, p < 0.001), while both of these methods correlated moderately with TAG for GCS (r = 0.479, p < 0.001 for CMR-FT vs. TAG; r = 0.548 for CT-FT vs. TAG). Intraobserver and interobserver agreement was excellent in all techniques. Our findings show that, in elderly patients with severe aortic stenosis (AS), the FT algorithm performs equally well in CMR and cardiac CT datasets for the assessment of GLS and GCS, both in terms of reproducibility and agreement with the gold standard, TAG

Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial

Renal sympathetic denervation (RDN) is under investigation as a treatment option in patients with resistant hypertension (RH). Determinants of arterial compliance may, however, help to predict the BP response to therapy. Aortic distensibility (AD) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR. This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes. We analyzed data of 65 patients with RH included in a multicenter trial. RDN was performed in all participants. A standardized CMR protocol was utilized at baseline and at 6-month follow-up. AD was determined as the change in cross-sectional aortic area per unit change in BP. Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg (p < 0.001) 6 months after RDN. Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm2 (p = 0.011). AD improved significantly by 33% from 1.52 ± 0.82 to 2.02 ± 0.93 × 10-3 mmHg-1 (p < 0.001). Increase of AD at follow-up was significantly more pronounced in younger patients (p = 0.005) and responders to RDN (p = 0.002). Patients with high-baseline AD were significantly younger (61.4 ± 10.1 vs. 67.1 ± 8.4 years, p = 0.022). However, there was no significant correlation of baseline AD to response to RDN. AD is improved after RDN across all age groups. Importantly, these improvements appear to be unrelated to observed BP changes, suggesting that RDN may have direct effects on the central vasculature

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The influence of renal sympathetic denervation on diastolic heart failure assessed by cardiovascular MRI

Renal denervation (RDN) significantly reduces blood pressure (BP) and improves myocardial function in patients with resistant hypertension. This multicenter study aimed to investigate the intermediate term effect of RDN on structural and functional myocardial parameters in patients with proven heart failure with preserved ejection fraction (HFpEF), assessed by cardiac magnetic resonance imaging (CMR). We analyzed data from 22 patients with HFpEF. 16 patients underwent renal denervation (RDN) as invasive treatment. A total of 6 matched control patients received optimal medical therapy (OMT). Both groups had diastolic heart failure defined by preserved ejection fraction (EF ≥ 50%) and pathologically elevated global longitudinal strain (GLS) at baseline (GLS>-18%) quantified by CMR. A standardized CMR protocol was performed at baseline and 6 months follow-up. Systolic and diastolic BP improved significantly with RDN: 167.88mmHg ±24.01 vs. 141.67mmHg ±16.62 systolic BP (p -18%). Bei allen Patienten erfolgte zum Zeitpunkt 0 und nach 6 Monaten eine CMR-Untersuchung nach einem standardisierten Protokoll. Der systolische und diastolische BD sank bei RDN-Patienten signifikant von systolisch 167,88mmHg ±24,01 auf 141,67mmHg ±16,62 (p<0,001) und diastolisch von 91,04mmHg ±15,99 auf 79,17mmHg ±15,68 (p=0,006). In der Kontrollgruppe fand keine signifikante Änderung des Blutdrucks statt (systolisch von 151,5mmHg ±20,79 auf 135,5mmHg ±24,68, p=0,129; diastolisch von 80,5mmHg ±10,99 auf 68,0mmHg ±10,56, p=0,061). Der GLS verbesserte sich in der RDN-Gruppe nach 6 Monaten signifikant um 21% von -14,21% ±3,19 auf -17,17% ±3,1 (p = 0,007). In der Kontrollgruppe mit OMT blieb der GLS weitgehend konstant (Zeitpunkt 0: -15,89% ±2,73, 6 Monate: -15,59% ±2,68, p=0,814). Der linksventrikuläre Massenindex (LVMI) sank in der RDN-Gruppe nach 6 Monaten, jedoch ohne statistische Signifikanz (von 58,55g/m² ±11,37 auf 55,46g/m² ±12,76; p=0,085). In der OMT-Gruppe blieb der LVMI auf gleichem Niveau (Zeitpunkt 0: 49,25g/m² ±8,2, 6 Monate: 50,18g/m² ±7,27, p=0,665). Unsere Ergebnisse deuten darauf hin, dass Patienten mit HFpEF hinsichtlich struktureller und funktioneller Myokardparameter von der RDN im Vergleich zu Patienten mit OMT profitieren. Die Auswirkungen der Therapie auf das klinische Ergebnis und die Leistungsfähigkeit der Patienten müssen jedoch in größeren Studien mit einem längeren Beobachtungszeitraum weiter untersucht werden

Multilayer myocardial strain improves the diagnosis of heart failure with preserved ejection fraction

Aims: The diagnostic and treatment of patients with heart failure with preserved ejection fraction (HFpEF) are both hampered by an incomplete understanding of the pathophysiology of the disease. Novel imaging tools to adequately identify these patients from individuals with a normal cardiac function and respectively patients with HF with reduced EF are warranted. Computing multilayer myocardial strain with feature tracking is a fast and accurate method to assess cardiac deformation. Our purpose was to assess the HFpEF diagnostic ability of multilayer strain parameters and compare their sensitivity and specificity with other established parameters. Methods and results: We included 20 patients with a diagnosis of HFpEF and, respectively, 20 matched controls. We assessed using feature-tracking cardiac magnetic resonance longitudinal and circumferential myocardial strain at three distinct layers of the myocardium: subendocardial (Endo-), mid-myocardial (Myo-), and subepicardial (Epi-). Comparatively, we additionally assessed various others clinical, imaging, and biochemical parameters with a putative role in HFpEF diagnostic: left ventricular end-diastolic volume (LVEDV), left ventricular mass (LVM), interventricular septum (IVS) wall thickness and free wall thickness, left atrial volume and strain, septal and lateral mitral annular early diastolic velocity (e`), E/e' ratio, and plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Global longitudinal strain (GLS) is significantly impaired at Endo (-20.8 ± 4.0 vs. -23.2 ± 3.4,P = 0.046), Myo- (-18.0 ± 3.0 vs. -21.0 ± 2.5,P = 0.002), and Epi- (-12.2 ± 2.0 vs. -16.2 ± 2.5,P < 0.001) levels. Compared with any other imaging parameter, an Epi-GLS lower than 13% shows the highest ability to detect patients with HFpEF [area under the curve (AUC) = 0.90 (0.81-1),P < 0.001] and in tandem with NT-proBNP can diagnose with maximal sensibility (93%) and specificity (100%), patients with HFpEF from normal, composed variable [AUC = 0.98 (0.95-1),P < 0.001]. In a logistic regression model, a composite predictive variable taking into account both GLS Epi and NT-proBNP values in each individual subject reached a sensitivity of 89% and a specificity of 100% with an AUC of 0.98 (0.95-1),P < 0.001, to detect HFpEF. Conclusions: Epi-GLS is a promising new imaging parameter to be considered in the clinical assessment of HFpEF patients. Given its excellent specificity, in tandem with a highly sensitive parameter such as NT-proBNP, Epi-GLS holds the potential to greatly improve the current diagnostic algorithms

Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial

Renal sympathetic denervation (RDN) is under investigation as a treatment option in patients with resistant hypertension (RH). Determinants of arterial compliance may, however, help to predict the BP response to therapy. Aortic distensibility (AD) is a well-established parameter of aortic stiffness and can reliably be obtained by CMR. This analysis sought to investigate the effects of RDN on AD and to assess the predictive value of pre-treatment AD for BP changes. We analyzed data of 65 patients with RH included in a multicenter trial. RDN was performed in all participants. A standardized CMR protocol was utilized at baseline and at 6-month follow-up. AD was determined as the change in cross-sectional aortic area per unit change in BP. Office BP decreased significantly from 173/92 ± 24/16 mmHg at baseline to 151/85 ± 24/17 mmHg (p < 0.001) 6 months after RDN. Maximum aortic areas increased from 604.7 ± 157.7 to 621.1 ± 157.3 mm[superscript 2] (p = 0.011). AD improved significantly by 33% from 1.52 ± 0.82 to 2.02 ± 0.93 × 10[superscript −3] mmHg[superscript −1] (p < 0.001). Increase of AD at follow-up was significantly more pronounced in younger patients (p = 0.005) and responders to RDN (p = 0.002). Patients with high-baseline AD were significantly younger (61.4 ± 10.1 vs. 67.1 ± 8.4 years, p = 0.022). However, there was no significant correlation of baseline AD to response to RDN. AD is improved after RDN across all age groups. Importantly, these improvements appear to be unrelated to observed BP changes, suggesting that RDN may have direct effects on the central vasculature. Keywords: Renal denervation, Aortic distensibility, Compliance, Vascular stiffness, Cardiovascular magnetic resonance, CMR, Resistant hypertensio

CMR tissue characterization in patients with HFmrEF

The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40–50%) are still unclear. Advanced cardiac MRI o ers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (15.7 2.1) and GCS (19.9 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 40 ms) and HFrEF (1033 54 ms) compared to healthy controls (972 31 ms) and HFpEF (985 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 3.4 ms) and HFrEF (56.0 6.0 ms) compared to healthy controls (50.6 2.1 ms). Di erences in ECV did not reach statistical significance. HFmrEF di ers from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation

Variability of Myocardial Strain During Isometric Exercise in Subjects With and Without Heart Failure

ackground: Fast strain-encoded cardiac magnetic resonance imaging (cMRI, fast-SENC) is a novel technology potentially improving characterization of heart failure (HF) patients by quantifying cardiac strain. We sought to describe the impact of isometric handgrip exercise (HG) on cardiac strain assessed by fast-SENC in HF patients and controls. Methods: Patients with stable HF and controls were examined using cMRI at rest and during HG. Left ventricular (LV) global longitudinal strain (GLS) and global circumferential (GCS) were derived from image analysis software using fast-SENC. [...]