Implication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature.

Neuronal differentiation-the development of neurons from neural stem cells-involves neurite outgrowth and is a key process during the development and regeneration of neural functions. In addition to various chemical signaling mechanisms, it has been suggested that thermal stimuli induce neuronal differentiation. However, the function of physiological subcellular thermogenesis during neuronal differentiation remains unknown. Here we create methods to manipulate and observe local intracellular temperature, and investigate the effects of noninvasive temperature changes on neuronal differentiation using neuron-like PC12 cells. Using quantitative heating with an infrared laser, we find an increase in local temperature (especially in the nucleus) facilitates neurite outgrowth. Intracellular thermometry reveals that neuronal differentiation is accompanied by intracellular thermogenesis associated with transcription and translation. Suppression of intracellular temperature increase during neuronal differentiation inhibits neurite outgrowth. Furthermore, spontaneous intracellular temperature elevation is involved in neurite outgrowth of primary mouse cortical neurons. These results offer a model for understanding neuronal differentiation induced by intracellular thermal signaling.

Incremental value of tricuspid annular enlargement to progressive tricuspid regurgitation in patients with longstanding persistent atrial fibrillation.

Tricuspid annular enlargement in patients with atrial fibrillation (AF) can induce tricuspid regurgitation (TR). However, risk factors associated with TR progression in patients with AF have not been defined. This study aimed to clarify an association between tricuspid annular diameter (TAD) and TR progression in patients with longstanding persistent AF. We retrospectively analyzed data from 228 patients who had longstanding persistent AF for > 1 year and mild or less TR on baseline echocardiograms. We defined significant TR as moderate or greater TR, graded according to the jet area and vena contracta. The optimal cut-off value of the TAD index (TADI), based on body surface area for predicting progression to significant TR, was estimated using receiver operating characteristic (ROC) curves. The independence and incremental value of the TADI were evaluated using multivariate Cox proportional hazard regression analysis and likelihood ratio tests. Over a median follow-up of 3.7 years, 55 (24.1%) patients developed significant TR. The optimal cut-off value of 21.1 mm/m2 for the TADI at baseline and ROC curves predicted TR progression with 70.4% sensitivity and 86% specificity. Furthermore, TADI was an independent predictor of TR progression (hazard ratio, 1.32; 95% confidence interval, 1.17-1.49, P < 0.001) and had a significant incremental value that exceeded that of models constructed using clinical parameters. In conclusion, TADI was significantly associated with TR progression and was an independent predictor of TR progression in longstanding persistent AF.

Association between gardening activity and frailty in patients with heart failure.

Objective Frailty is common in patients with heart failure (HF). Given that gardening demands regular physical activity and offers therapeutic relaxation benefits, this activity may reduce frailty. We investigated the association between gardening activities and frailty in patients with HF. Methods, patients, or materials Between August 2022 and March 2023, we surveyed patients at risk of HF and those with HF who regularly attended a cardiology outpatient clinic. Gardening activities were defined as the ongoing cultivation of flowers, vegetables, or fruits for more than a year. The questionnaire assessed the presence or absence of gardening activities as well as the frequency, duration per session, years of experience, and scale of such activities. We calculated the frailty index. Frailty was defined as a frailty index of 0.25 or greater. Results Of the 1,277 respondents, 69% engaged in gardening and 35% were frail. After adjusting for multiple confounding factors, gardening activities showed an inverse association with frailty [odds ratio = 0.723, 95% confidence interval (0.533-0.981)]. Moreover, frailty and the frailty index showed an inverse association with more extended and large-scale gardening activities. Conclusion Gardening activities were thus found to be associated with a low prevalence of frailty in patients with HF.

Mice Lacking PLAP-1/Asporin Show Alteration of Periodontal Ligament Structures and Acceleration of Bone Loss in Periodontitis.

Periodontal ligament-associated protein 1 (PLAP-1), also known as Asporin, is an extracellular matrix protein expressed in the periodontal ligament and plays a crucial role in periodontal tissue homeostasis. Our previous research demonstrated that PLAP-1 may inhibit TLR2/4-mediated inflammatory responses, thereby exerting a protective function against periodontitis. However, the precise roles of PLAP-1 in the periodontal ligament (PDL) and its relationship to periodontitis have not been fully explored. In this study, we employed PLAP-1 knockout mice to investigate its roles and contributions to PDL tissue and function in a ligature-induced periodontitis model. Mandibular bone samples were collected from 10-week-old male C57BL/6 (WT) and PLAP-1 knockout (KO) mice. These samples were analyzed through micro-computed tomography (µCT) scanning, hematoxylin and eosin (HE) staining, picrosirius red staining, and fluorescence immunostaining using antibodies targeting extracellular matrix proteins. Additionally, the structure of the PDL collagen fibrils was examined using transmission electron microscopy (TEM). We also conducted tooth extraction and ligature-induced periodontitis models using both wild-type and PLAP-1 KO mice. PLAP-1 KO mice did not exhibit any changes in alveolar bone resorption up to the age of 10 weeks, but they did display an enlarged PDL space, as confirmed by µCT and histological analyses. Fluorescence immunostaining revealed increased expression of extracellular matrix proteins, including Col3, BGN, and DCN, in the PDL tissues of PLAP-1 KO mice. TEM analysis demonstrated an increase in collagen diameter within the PDL of PLAP-1 KO mice. In line with these findings, the maximum stress required for tooth extraction was significantly lower in PLAP-1 KO mice in the tooth extraction model compared to WT mice (13.89 N ± 1.34 and 16.51 N ± 1.31, respectively). In the ligature-induced periodontitis model, PLAP-1 knockout resulted in highly severe alveolar bone resorption, with a higher number of collagen fiber bundle tears and significantly more osteoclasts in the periodontium. Our results demonstrate that mice lacking PLAP-1/Asporin show alteration of periodontal ligament structures and acceleration of bone loss in periodontitis. This underscores the significant role of PLAP-1 in maintaining collagen fibrils in the PDL and suggests the potential of PLAP-1 as a therapeutic target for periodontal diseases.

Imaging flow cytometry-based multiplex FISH for three IGH translocations in multiple myeloma.

Three types of chromosomal translocations, t(4;14)(p16;q32), t(14;16)(q32;q23), and t(11;14)(q13;q32), are associated with prognosis and the decision making of therapeutic strategy for multiple myeloma (MM). In this study, we developed a new diagnostic modality of the multiplex FISH in immunophenotyped cells in suspension (Immunophenotyped-Suspension-Multiplex (ISM)-FISH). For the ISM-FISH, we first subject cells in suspension to the immunostaining by anti-CD138 antibody and, then, to the hybridization with four different FISH probes for genes of IGH, FGFR3, MAF, and CCND1 tagged by different fluorescence in suspension. Then, cells are analyzed by the imaging flow cytometry MI-1000 combined with the FISH spot counting tool. By this system of the ISM-FISH, we can simultaneously examine the three chromosomal translocations, i.e, t(4;14), t(14;16), and t(11;14), in CD138-positive tumor cells in more than 2.5 × 104 nucleated cells with the sensitivity at least up to 1%, possibly up to 0.1%. The experiments on bone marrow nucleated cells (BMNCs) from 70 patients with MM or monoclonal gammopathy of undetermined significance demonstrated the promising qualitative diagnostic ability in detecting t(11;14), t(4;14), and t(14;16) of our ISM-FISH, which was more sensitive compared with standard double-color (DC) FISH examining 200 interphase cells with its best sensitivity up to 1.0%. Moreover, the ISM-FISH showed a positive concordance of 96.6% and negative concordance of 98.8% with standard DC-FISH examining 1000 interphase cells. In conclusion, the ISM-FISH is a rapid and reliable diagnostic tool for the simultaneous examination of three critically important IGH translocations, which may promote risk-adapted individualized therapy in MM.

Role of the right ventricular contractile reserve during low-load exercise in predicting heart failure readmission.

BACKGROUND: Exercise intolerance in patients with heart failure (HF) increases HF-associated readmission, and right ventricular (RV) contractile reserve assessed by low-load exercise stress echocardiography (ESE) is associated with exercise intolerance. This study investigated the impact of RV contractile reserve evaluated by low-load ESE on HF readmission. METHODS: We prospectively examined 81 consecutive patients hospitalized for HF who underwent low-load ESE under a stabilized HF condition between May 2018 and September 2020. We performed a 25-W low-load ESE and defined RV contractile reserve as the increment in RV systolic velocity (RV s'). The primary outcome was hospital readmission. Incremental values of the change in RV s' over a readmission risk (RR) score were analyzed using the receiver operating characteristic (ROC) area under the curve; internal validation using bootstrapping was performed. The association between RV contractile reserve and HF readmission was illustrated with the Kaplan-Meier curve. RESULTS: Eighteen (22 %) patients were readmitted due to worsening HF during the observation period (median 15.6 months). The cut-off value of 0.68 cm/s for the change in RV s' to predict HF readmission with the ROC curve analysis indicated good sensitivity (100 %) and specificity (76.2 %). The discriminatory ability for HF readmission was significantly improved by adding the change in RV s' to the RR score (p = 0.006), and the c-statistic using the bootstrap method was 0.92. The cumulative survival rate free of HF readmission was significantly lower in patients with reduced-RV contractile reserve (log-rank test, p < 0.001). CONCLUSIONS: The change in RV s' during low-load exercise had an incremental prognostic value for predicting HF readmission. The results demonstrated the loss of RV contractile reserve assessed by low-load ESE was associated with HF readmission.

Usefulness of intravascular ultrasound assessment after development of the slow flow phenomenon during percutaneous coronary intervention.

The slow flow phenomenon is a critical complication during percutaneous coronary intervention (PCI) that leads to poor outcomes. We aimed to evaluate the mechanisms underlying the slow flow phenomenon using intravascular ultrasound (IVUS). We retrospectively analyzed IVUS data from 62 lesions in 58 consecutive patients who experienced the slow flow phenomenon during PCI. IVUS was performed immediately after the development of the slow flow phenomenon to assess its cause. No IVUS-based evidence of mechanical obstruction was categorized as distal embolization. Distal embolization was observed in 46 lesions (74%). The slow flow phenomenon occurred in all these lesions after stent implantation. In addition to distal embolization, three different mechanisms underlying the induction of the slow flow phenomenon due to mechanical obstructions (16 lesions, 26%) were detected on IVUS, namely, medial dissection/hematoma (6 lesions), intimal flap (6 lesions), and thrombus obstruction (4 lesions). Most mechanical obstructions (13 lesions, 81%) could not be identified by angiography alone. In 15/16 lesions (94%) with mechanical obstruction, deteriorated flow improved immediately after balloon dilatation or bail-out stent implantation, although intracoronary vasodilator administration could not reestablish coronary flow. The frequency of mechanical obstruction as the cause of the slow flow phenomenon was relatively high. Given the difficulty in angiographical differentiation, IVUS-guided management of slow flow may be a useful strategy.

Left ventricular longitudinal strain is a major determinant of CT-derived three-dimensional maximum principal strain: comparison with two-dimensional speckle tracking echocardiography.

Computed tomography (CT)-derived three-dimensional maximum principal strain (MP-strain) can provide incremental value to coronary CT angiography for cardiac dysfunction assessment with high diagnostic performance in patients with myocardial infarction. Global longitudinal strain (GLS) measured using two-dimensional speckle tracking echocardiography (2D-STE) is more sensitive than left ventricular ejection fraction (LVEF) for detecting early myocardial dysfunction. We aimed to compare CT-derived MP-strain with each of 2D-STE-derived strains (i.e., longitudinal, circumferential, and radial strains), and identify the major determinants of CT-derived MP-strain among 2D-STE-derived strains. We studied 51 patients who underwent cardiac CT and echocardiography. CT images were reconstructed at every 5% (0-95%) of the RR interval. A dedicated workstation was used to analyze CT-derived MP-strain on the 16-segment model. We calculated CT-derived global MP-strain with all the 16 segments on a per patient basis. Pearson's test was used to assess correlations between CT-derived MP-strain and STE-strain at global and segmental levels. The intra-class correlation coefficient for interobserver agreement for CT-derived global MP-strain was 0.98 (95% confidence interval 0.96-0.99). The low-CT-derived global MP-strain group (≤ 0.43) had more patients with LV dysfunction than the high-CT-derived global MP-strain group (> 0.43). CT-derived global MP-strain was associated with STE-GLS (r = 0.738, P < 0.001), global circumferential strain (r = 0.646, P < 0.001), and global radial strain (r = 0.432, P = 0.001). In multivariate analysis, STE-GLS had the strongest association to CT-derived global MP-strain among three directional STE-strains and LVEF by echocardiography (standardized coefficient = - 0.527, P < 0.001). STE-GLS is a major determinant of CT-derived global MP-strain. CT-derived MP-strain may enhance the value of coronary CT angiography by adding functional information to CT-derived LVEF.

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species.

Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment. We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germ layer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stem cells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestock mammals, pluripotent stem cells related to the formative embryonic disc are reliably established using a common and defined signalling environment. This article has an associated 'The people behind the papers' interview.

Disabling de novo DNA methylation in embryonic stem cells allows an illegitimate fate trajectory.

Genome remethylation is essential for mammalian development but specific reasons are unclear. Here we examined embryonic stem (ES) cell fate in the absence of de novo DNA methyltransferases. We observed that ES cells deficient for both Dnmt3a and Dnmt3b are rapidly eliminated from chimeras. On further investigation we found that in vivo and in vitro the formative pluripotency transition is derailed toward production of trophoblast. This aberrant trajectory is associated with failure to suppress activation of Ascl2Ascl2 encodes a bHLH transcription factor expressed in the placenta. Misexpression of Ascl2 in ES cells provokes transdifferentiation to trophoblast-like cells. Conversely, Ascl2 deletion rescues formative transition of Dnmt3a/b mutants and improves contribution to chimeric epiblast. Thus, de novo DNA methylation safeguards against ectopic activation of Ascl2 However, Dnmt3a/b-deficient cells remain defective in ongoing embryogenesis. We surmise that multiple developmental transitions may be secured by DNA methylation silencing potentially disruptive genes.

Mouse Model of Loeys-Dietz Syndrome Shows Elevated Susceptibility to Periodontitis via Alterations in Transforming Growth Factor-Beta Signaling.

Loeys-Dietz syndrome (LDS) is a syndromic connective tissue disorder caused by a heterozygous missense mutation in genes that encode transforming growth factor (TGF)-ß receptor (TGFBR) 1 and 2. We encountered a patient with LDS, who had severe periodontal tissue destruction indicative of aggressive periodontitis. The patient had a missense mutation in the glycine and serine-rich domain of TGFBR1 exon 3. This G-to-T mutation at base 563 converted glycine to valine. We established an LDS model knock-in mouse that recapitulated the LDS phenotype. Homozygosity of the mutation caused embryonic lethality and heterozygous knock-in mice showed distorted and ruptured elastic fibers in the aorta at 24 weeks of age and died earlier than wildtype (WT) mice. We stimulated mouse embryonic fibroblasts (MEFs) from the knock-in mouse with TGF-ß and examined their responses. The knock-in MEFs showed downregulated Serpine 1 mRNA expression and phosphorylation of Smad2 to TGF-ß compared with WT MEFs. To clarify the influence of TGF-ß signaling abnormalities on the pathogenesis or progression of periodontitis, we performed pathomolecular analysis of the knock-in mouse. There were no structural differences in periodontal tissues between WT and LDS model mice at 6 or 24 weeks of age. Micro-computed tomography revealed no significant difference in alveolar bone resorption between WT and knock-in mice at 6 or 24 weeks of age. However, TGF-ß-related gene expression was increased significantly in periodontal tissues of the knock-in mouse compared with WT mice. Next, we assessed a mouse periodontitis model in which periodontal bone loss was induced by oral inoculation with the bacterial strain Porphyromonas gingivalis W83. After inoculation, we collected alveolar bone and carried out morphometric analysis. P. gingivalis-induced alveolar bone loss was significantly greater in LDS model mice than in WT mice. Peritoneal macrophages isolated from Tgfbr1 G188V/+ mice showed upregulation of inflammatory cytokine mRNA expression induced by P. gingivalis lipopolysaccharide compared with WT macrophages. In this study, we established an LDS mouse model and demonstrated that LDS model mice had elevated susceptibility to P. gingivalis-induced periodontitis, probably through TGF-ß signal dysfunction. This suggests that TGF-ß signaling abnormalities accelerate the pathogenesis or progression of periodontitis.

Restricted left atrial dilatation can visually differentiate cardiac amyloidosis from hypertrophic cardiomyopathy.

AIMS: Cardiac amyloidosis (CA) is an infiltrative myocardial disease that occasionally mimics hypertrophic cardiomyopathy (HCM). The aim of this study is to investigate the discriminatory ability of visual assessment of left atrial (LA) function between CA and HCM on echocardiography. METHODS AND RESULTS: In total, 93 patients with cardiac magnetic resonance imaging (CMR)-confirmed HCM and 34 with cardiac biopsy-confirmed CA were retrospectively assessed. LA dilatation was assessed via echocardiography in an apical four-chamber view. Visual assessment was performed to identify LA dilatation grade (preserved = 1, abnormal = 2, and restricted = 3) based on the extent of outward expansion in the LA reservoir phase. Regarding the reproducibility of visually assessing LA dilatation grade, the kappa values between intra- and inter-observer measurements were 0.82 and 0.70, respectively. Of 127 participants, 57 (45%), 42 (33%), and 28 (22%) presented with LA dilatation Grades 1, 2, and 3, respectively. All 57 patients with preserved LA dilatation (Grade 1) had HCM, and 20 of 28 patients (71%) with restricted LA dilatation (Grade 3) presented with CA. Patients with CA had a higher LA dilatation grade than those with HCM (P < 0.01). LA emptying fraction and reservoir strain were also quantitatively evaluated. The area under the curves of LA dilatation grade (0.88) and LA emptying fraction (0.88) for differentiation of these two diseases were higher than that of LA reservoir strain (0.73) (P < 0.01, respectively). During follow-up, nine patients with HCM and 16 with CA experienced cardiac event (cardiac death or hospitalization due to heart failure). In Kaplan-Meier analysis including both groups of HCM and CA, the incidence of cardiac events was higher in patients with restricted LA dilatation than in those with preserved or abnormal LA dilatation (log-rank test, P < 0.01). CONCLUSIONS: Restricted LA dilatation is an indicator for the diagnosis of CA. Further, visual assessment of abnormal LA motion may facilitate diagnosis in patients with CA and high-risk patients with HCM.

Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion.

Adipose tissue fibrosis with chronic inflammation is a hallmark of obesity-related metabolic disorders, and the role of proteoglycans in developing adipose tissue fibrosis is of interest. Periodontal disease is associated with obesity; however, the underlying molecular mechanisms remain unclear. Here we investigated the roles of periodontal ligament associated protein-1 (PLAP-1)/asporin, a proteoglycan preferentially and highly expressed in the periodontal ligament, in obesity-related adipose tissue dysfunction and adipocyte differentiation. It was found that PLAP-1 is also highly expressed in white adipose tissues. Plap-1 knock-out mice counteracted obesity and alveolar bone resorption induced by a high-fat diet. Plap-1 knock-down in 3T3-L1 cells resulted in less lipid accumulation, and recombinant PLAP-1 enhanced lipid accumulation in 3T3-L1 cells. In addition, it was found that primary preadipocytes isolated from Plap-1 knock-out mice showed lesser lipid accumulation than the wild-type (WT) mice. Furthermore, the stromal vascular fraction of Plap-1 knock-out mice showed different extracellular matrix gene expression patterns compared to WT. These findings demonstrate that PLAP-1 enhances adipogenesis and could be a key molecule in understanding the association between periodontal disease and obesity-related metabolic disorders.

Effect of Molecular Architecture on Associating Behavior of Star-Like Amphiphilic Polymers Consisting of Plural Poly(ethylene oxide) and One Alkyl Chain.

Associating behavior of star-like amphiphilic polymers consisting of two or three poly(ethylene oxide) (PEO) chains and one stearyl chain (C18) was investigated. Although the aggregation number (Nagg) of linear analogue of amphiphilic polymers monotonically decreased with increasing number-average molecular weight of PEO (Mn,PEO), the Nagg of micelles of star-like amphiphilic polymers with Mn,PEO = 550 g/mol was smaller than that with Mn,PEO = 750 g/mol, whereas that with Mn,PEO ≥ 750 g/mol showed general Mn,PEO dependence. Small-angle X-ray scattering analyses revealed that the occupied area of one PEO chain on the interface between hydrophobic core and corona layer in the micelles of star-like polymers was much narrower than that in the linear amphiphilic polymers. This result indica ted the PEO chains of star-like polymers partially took unfavorable conformation near the core-corona interface in polymer micelles. The effect of local conformation of PEO chains near the interface on the associating behavior became significant as Mn,PEO decreased. Therefore, in polymer micelles of star-like amphiphilic polymers containing PEO with Mn,PEO = 550 g/mol, the enlargement of occupied area of PEO on the core-corona interface should be caused to avoid the formation of unfavorable conformations of partial PEO chains, resulting in a decrease in Naggs.

Capture of Mouse and Human Stem Cells with Features of Formative Pluripotency.

Pluripotent cells emerge as a naive founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs) represent the initial naive and final primed phases of pluripotency, respectively. Here, we investigate the intermediate formative stage. Using minimal exposure to specification cues, we derive stem cells from formative mouse epiblast. Unlike ESCs or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonize somatic tissues and germline in chimeras. Whole-transcriptome analyses show similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells show distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naive cells or embryos support expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.

Impact of right ventricular contractile reserve during low-load exercise on exercise intolerance in heart failure.

AIMS: Traditional criteria for heart transplantation by cardiopulmonary exercise testing (CPX) include peak oxygen uptake (VO2 ) < 14 mL/kg/min. Reaching a sufficient exercise load is challenging for patients with refractory heart failure (HF) because of their exercise intolerance. Recently, a substantial impact of right ventricular (RV) dysfunction was highlighted on urgent heart transplantation and mortality. This study aims to investigate the impact of RV contractile reserve, assessed by low-load exercise stress echocardiography (ESE), on exercise intolerance defined as peak VO2  < 14 mL/kg/min, in patients with HF. METHODS AND RESULTS: We prospectively examined 67 consecutive patients hospitalized for HF who underwent ESE and CPX under a stabilized HF condition. Although low-load ESE was defined as 25 W load exercise, an increment in RV systolic (s') velocity was regarded as the preservation of RV contractile reserve. All patients completed low-load ESE. During low-load ESE, the variation in RV s' velocity significantly correlated with peak VO2 (r = 0.787, P < 0.001). The change in RV s' velocity during low-load ESE accurately identified patients with peak VO2  < 14 mL/kg/min (area under the curve, 0.95; sensitivity, 92%; specificity, 85%). The intraclass correlation coefficient for intra-observer and inter-observer agreement for the change in RV s' velocity was 0.96 (95% confidence interval, 0.88-0.99, P < 0.001) and 0.86 (95% confidence interval, 0.64-0.95, P < 0.001), respectively. The RV-to-pulmonary circulation (PC) coupling, which was assessed by the slope of the relationship between RV s' velocity and pulmonary artery systolic pressure at rest and low-load exercise, was worse in the low-peak VO2 group (<14 mL/kg/min) than the preserved-peak VO2 group (≥14 mL/kg/min). CONCLUSIONS: The change in RV s' velocity during low-load ESE could estimate the exercise capacity in HF patients. The assessments of RV contractile reserve and RV-to-PC coupling could be clinically beneficial to distinguish high-risk HF patients.

Characteristics of the left ventricular three-dimensional maximum principal strain using cardiac computed tomography: reference values from subjects with normal cardiac function.

OBJECTIVES: This study evaluated the characteristics of left ventricular maximum principal strain (LV-MPS) using cardiac CT in subjects with normal LV function. METHODS: Of 973 subjects who underwent retrospective electrocardiogram-gated cardiac CT using a third-generation dual-source CT without beta-blocker administration, 31 subjects with preserved LV ejection fraction ≥ 55% assessed by echocardiography without coronary artery stenosis and cardiac pathology were retrospectively identified. CT images were reconstructed every 5% (0-95%) of the RR interval. LV-MPS and the time to peak (TTP) were analyzed using the 16-segment model and compared among three levels (base, mid, and apex) and among four regions (anterior, septum, inferior, and lateral) using the Steel-Dwass test. The intra- and inter-observer reproducibilities for LV-MPS were calculated using intraclass correlation coefficients (ICCs). RESULTS: The intra- and inter-observer ICCs (95% confidence interval) for peak LV-MPS were 0.96 (0.94-0.97) and 0.94 (0.92-0.96), respectively. The global peak LV-MPS (median, inter-quantile range) was 0.59 (0.55-0.72). The regional LV-MPS significantly increased in the order of the basal (0.54, 0.49-0.59), mid-LV (0.57, 0.53-0.65), and apex (0.68, 0.60-0.84) (p < 0.05, in each), and was significantly higher in the lateral wall (0.66, 0.60-0.77), while that in the septal region (0.47, 0.44-0.54) was the lowest among the four LV regions (all p < 0.05). No significant difference in TTP was seen among the myocardial levels and regions. CONCLUSION: CT-derived LV-MPS is reproducible and quantitatively represents synchronized myocardial contraction with heterogeneous values in subjects with normal LV function. KEY POINTS: • CT-derived left ventricular maximum principal strain analysis allows highly reproducible quantitative assessments of left ventricular myocardial contraction. • In subjects with normal cardiac function, the peak value of CT-derived left ventricular maximum principal strain is the highest in the apical level and in the lateral wall and the lowest in the septum. • The regional peak left ventricular maximum principal strain shows intra-ventricular heterogeneity on a per-patient basis, but myocardial contraction is globally synchronized in subjects with normal cardiac function seen on cardiac CT.