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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Objective Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. Method We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. Results The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. Conclusions This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

Background Two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be useful for the diagnosis of myocardial ischemia by detecting delayed relaxation (diastolic stunning) after an episode of angina. 2D-longitudinal strain is not specific besides ischemia such as diastolic dysfunction, and diabetes have been associated with abnormal longitudinal fibers. The aim is to evaluate the diagnostic accuracy of Left ventricular (LV) diastolic transverse strain imaging by STE to detect the presence of acute coronary syndrome (ACS) in diabetic patients with acute chest pain. Methods 385 consecutive patients with acute chest pain and without wall motion abnormality, who were admitted to an emergency department (ED) at 1 of 12 clinical sites in Japan, were enrolled and underwent 2D-STE at ED. Left ventricular (LV) transverse strain values at aortic valve closure (A) and one-third of diastole duration (B) were measured. The strain imaging diastolic index (SI-DI) was value was determined as: (A − B)/A × 100% to assess the LV diastolic strain imaging and was used to identify the regional LV delayed relaxation. All patients underwent coronary CT or coronary angiography to establish the diagnosis of ACS. Clinicians were blinded to the 2D-STE results. Results Out of 385 patients, 2D-STE analysis was possible in 365 patients (94%). 76 patients were diabetic (DM+), and 289 patients were non-diabetic (DM-). With assessment of coronary CT or coronary angiography, ACS was diagnosed in 125 patients (34%). 2D-STE was obtained at a mean of 5.3 hours after chest pain episode. Transverse SI-DI of ischemic segments were significantly lower than those of non-ischemic segments (p value Conclusion LV diastolic transverse strain imaging by 2D-STE at ED increase the sensitivity, specificity and accuracy to predict the presence of ACS in diabetic patients with chest pain, as well as non-diabetic patients. (UMIN000013859). Figure 1. Transverse Strain (SI-DI): AUC (95% CI) Funding Acknowledgement Type of funding source: None

Background/Introduction The right bundle branch block (RBBB) has been considered a benign finding in asymptomatic individuals. However, this concept based on a few, old, small sample size studies. Recently, the importance of the right ventricular dysfunction was focused on cardiovascular prognosis in clinical cardiology. Purpose To determine the prognostic value of RBBB in community-based health checkups cohort with a large sample size in recent years in Japan. Methods We assessed 88,089 individuals (mean age, 58.3±10.2 years; 66.1% women) who participated in annual community-based health checkups. Exclusion criteria were current or previous history of heart disease, stroke, and intraventricular block such as left bundle branch block other than RBBB. We followed them from 1993 to 2016. The primary endpoint was cardiovascular death, or all-cause death. The Cox regression model was assessed in each gender. The variables included in the multivariate analyses were age, body mass index, systolic blood pressure, hypertension, total cholesterol level, high-density lipoprotein cholesterol level, treated-hyperlipidemia, hyperglycemia, treated-diabetes, estimated glomerular filtration rate (eGFR), current smoking, and drinking habit. Results The prevalence of RBBB was higher in men than women (723/29,863 2.4% in men vs. 581/58,204 1.0% in women, P In women, RBBB was associated with significantly increased cardiovascular mortality with multivariate-adjusted hazard ratios (HR) of 1.26 [95% confidence interval (CI), 1.03–1.54]. Then, we divided them into younger or elder groups according to the cut-off age of 65-year-old. In women ≤65-year-old, RBBB related to greater cardiovascular mortality with multivariate-adjusted HR of 1.89 [95% CI, 1.27–2.80]. However, in women >65-year-old, RBBB did not show the prognostic significance. In men, RBBB did not reach the significant results in all participants, however, men >65-year-old with RBBB showed the significant poor prognosis with HR of 1.26 [95% CI, 1.04–1.53]. Conclusions In this cohort study, contrary to common perception, RBBB was associated with increased cardiovascular mortality in women, especially younger women ≤65-year-old, and elderly men. To the extent we know, the present study is the largest and long-term follow-up study showing that the significance of RBBB differs depending on sex and age. Especially in young women who usually are less prone to show wide QRS, RBBB might represent the pathological abnormality. Although the pathophysiological effect of the RBBB on the cardiovascular outcome needs further investigation in the future, clinicians should alert the RBBB in young women and elder men even if they have no symptoms and evaluate the heart abnormality and follow them up carefully. Funding Acknowledgement Type of funding source: None

Background Prior study reported around one-third of cardiac sarcoidosis (CS) are considered as isolated CS. Detection of CS is challenging due to the limited sensitivity of endomyocardial biopsy and applicability of guidelines, especially in patients without extra-cardiac involvement. Existing diagnostic criteria by Japanese Ministry of health and Welfare (JMHW) or Heart Rhythm Society (HRS) require the presence of extra-cardiac sarcoidosis for clinical diagnosis, isolated CS is not diagnosable in the absence of a positive histological finding. Recently, Japanese Society of Cardiology (JCS) updated diagnostic criteria for CS, which provides the pathway to diagnose isolated CS. Purpose We aimed to assess the reliability of the updated CS guideline in diagnosing CS compared to the prior guidelines. Methods We retrospectively identified 162 consecutive patients who underwent FDG-PET for suspected CS from 2012 through 2019. According to the updated JCS diagnostic criteria, patients were classified as histologic diagnosis of CS, clinical diagnosis of CS, or isolated CS (Figure A). We compared the association between diagnostic criteria and response with anti-inflammatory therapy. Results The JCS criteria classified 24 patients (15%) as having clinical CS, 4 (3%) as histological diagnosis of CS, and 21 (13%) as isolated CS. The JMHW criteria defined 22 patients (14%) as having CS (clinical 11%, histological 3%) and HRS criteria classified 11 patients (7%) as having CS (clinical 4%, histological 3%). Extra-cardiac involvement was detected in 36 patients (22%) with 8% of histological confirmation. Among the 126 patients without extra-cardiac involvement, prevalence of cardiac involvement was higher in isolated CS (P Conclusions Updated JCS diagnostic criteria detects CS patients with active myocardial inflammation which require anti-inflammatory therapy regardless of extra-cardiac involvement better than the prior guidelines. Diagnostic criteria for CS Funding Acknowledgement Type of funding source: None

Funding Acknowledgements none OnBehalf A TRAC-SI Multicenter Trial Background Two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be useful for the diagnosis of myocardial ischemia by detecting delay in regional myocardial expansion (diastolic stunning) up to many hours after an episode of angina. The aim is to evaluate the diagnostic accuracy of Left ventricular (LV) diastolic longitudinal, circumferential, transverse and radial strain imaging by STE to detect the presence of acute coronary syndrome (ACS) in patients with acute chest pain. Methods 388 consecutive patients with acute chest pain and without wall motion abnormality, who were admitted to an emergency department (ED) at 1 of 12 clinical sites in Japan, were enrolled and underwent 2D-STE at ED. Left ventricular (LV) longitudinal, circumferential, transverse and radial strain values at aortic valve closure (A) and one-third of diastole duration (B) were measured. The strain imaging diastolic index (SI-DI) was value was determined as: (A-B)/A × 100% to assess the LV diastolic strain imaging and was used to identify the regional LV delayed relaxation. All patients underwent coronary CT or coronary angiography to establish the diagnosis of ACS. Clinicians were blinded to the 2D-STE results. Results Out of 388 patients, 2D-STE analysis was possible in 358 patients (92%). With assessment of coronary CT or coronary angiography, ACS was diagnosed in 118 patients (33%). 2D-STE was obtained at a mean of 5.3 hours after chest pain episode. SI-DI of longitudinal, circumferential, transverse and radial strain of ischemic segments were significantly lower than those of non-ischemic segments (p value < 0.001), and transverse and radial SI-DI demonstrated high diagnostic accuracy, compared with longitudinal SI-DI (Figure 1). Sensitivity, specificity, and negative predictive value for ACS of transverse SI-DI are 87%, 88%, % and 95%, respectively, using a cut-off value of 63.3. Conclusion LV diastolic strain imaging by 2D-STE at ED increase the sensitivity, specificity and accuracy to predict the presence of ACS in patients with chest pain. Compared with longitudinal diastolic strain imaging, transverse diastolic strain imaging is more sensitive marker to detect the myocardial ischemic episode (UMIN000013859). Abstract 1225 Figure 1

Aims Recently developed vector flow mapping (VFM) enables evaluation of local flow dynamics without angle dependency. This study used VFM to evaluate quantitatively the index of intraventricular haemodynamic kinetic energy in patients with left ventricular (LV) diastolic dysfunction and to compare those with normal subjects. Methods and results We studied 25 patients with estimated high left atrial (LA) pressure (pseudonormal: PN group) and 36 normal subjects (control group). Left ventricle was divided into basal, mid, and apical segments. Intraventricular haemodynamic energy was evaluated in the dimension of speed, and it was defined as the kinetic energy index. We calculated this index and created time-energy index curves. The time interval from electrocardiogram (ECG) R wave to peak index was measured, and time differences of the peak index between basal and other segments were defined as ΔT-mid and ΔT-apex. In both groups, early diastolic peak kinetic energy index in mid and apical segments was significantly lower than that in the basal segment. Time to peak index did not differ in apex, mid, and basal segments in the control group but was significantly longer in the apex than that in the basal segment in the PN group. ΔT-mid and ΔT-apex were significantly larger in the PN group than the control group. Multiple regression analysis showed sphericity index, E/E′ to be significant independent variables determining ΔT apex. Conclusion Retarded apical kinetic energy fluid dynamics were detected using VFM and were closely associated with LV spherical remodelling in patients with high LA pressure.

Aims To validate intramural strain measured by a speckle tracking imaging (STI) system against that measured by sonomicrometry crystals. Methods and results In 11 anaesthetized sheep, six sets of three sonomicrometry crystals were implanted in endo-, mid-wall, and epimyocardium on the anterior and lateral walls. Circumferential strain (CS) was calculated at three layers from endo-, mid-wall, and epicardial speckle. Radial strain (RS) was assessed for inner and outer halves of the myocardium. We compared ultrasound-derived strain measurements against those by sonomicrometry at baseline and during pharmacological stress and coronary occlusion. Intraclass correlation coefficients at baseline and during coronary occlusion were as follows: endocardial CS 0.80, 0.97; mid-wall CS 0.58, 0.89; epicardial CS 0.71, 0.81; endocardial RS 0.50, 0.78; epicardial RS 0.35, 0.83; and total RS 0.33, 0.71; respectively. At baseline, endocardial strains were higher than mid-wall and epicardial strains, resulting in an inner/outer wall RS gradient and inner/mid/outer wall CS gradients. Ischaemia caused significant reduction in all strains and disappearance of the strain gradient. Conclusion A newly developed STI system can accurately assess the intramural heterogeneity of CS distribution in normal and ischaemic myocardial segments and has the potential to become a non-invasive bedside tool for characterizing myocardial strain gradient.

Purpose: Controversy exists regarding prognosis in Paradoxical Low Flow Low Pressure Gradient (PLFLPG) severe Aortic Stenosis (AS) despite normal Left Ventricular Ejection Fraction (LVEF). Little is known about conversion rate from low Pressure Gradient (PG) to high PG during longitudinal study and its impact on prognosis. Methods: Among 220 patients with severe PLFLPG AS (indexed aortic valve area 50%), we selected 86 patients who had received more than 2 echo examinations at least 6 months apart. Patients were followed up, and Cardiac Death (CD) and Major Cardiovascular Events (MACEs), including CD, aortic valve replacement, non-fatal myocardial infarction and congestive heart failure were determined. Results: During a follow up for a median of 720 days from the first echo study, 2 patients died due to CD, and 14 patients developed MACEs. After a mean of 419 days from the first to the second echo examinations, 67 patients (78%) still remained low PG status and other 19 patients (22%) converted from low PG to high PG AS. Although no significant difference of CD was noted between the two groups, MACE was significantly higher in high PG group compared to low PG group. ![Figure][1] MACE-free survival of HPG/LPG group Conclusions: Overall, prognosis in Japanese patients with PLFLPG severe AS seems to be better compared to Western patients. However, conversion from low PG to high PG status occurred in 1/4 of patients during follow up, and this was associated with poorer prognosis. [1]: pending:yes

Left ventricular (LV) systolic wall strain is one of the new candidates for the prognostic indicator for the hypertensive heart failure. However, it is still unclear what underlying transmural structural remodeling corresponds strain abnormality in progression of hypertensive heart failure. Objective and methods: To investigate the relationship between the structural change and myocardial strain, 60 Dahl salt-sensitive rats fed a high-salt (HF-group) or a low-salt diet (Control-group) from 6-weeks age. Pressure-volume relationship was analyzed and lung weight was measured at 10, 14, and 18 weeks of age and assessed the heart failure stage. In each stage, transmural distribution of LV myocardial fiber angle, fibrosis, and myocyte hypertrophy were evaluated pathologically and related mRNA quantification were performed. LV global longitudinal (GLS) and circumferential strain (GCS) were measured using 2D speckle tracking echocardiography. Results: While, Emax was preserved throughout the study period, tau and EDPVR indicated progressive deterioration from 14 weeks (diastolic dysfunction stage). And lung weight was significantly increased at 18 weeks (decompensated stage). Myocardial fiber orientation did not change as disease progress. Fibrosis-area% in histology and collagen type I/ type III mRNA ratio were significantly elevated in subendocardial-layer at 14 weeks and propagated into mid-layer at 18 weeks. Myocyte hypertrophy and mRNA of embryonic type -myosin heavy chain increased in subendocardial-layer at 14 weeks and progress into mid-layer at 18 weeks. In compared to control-group, HT-group showed progressively deteriorated GLS at 14 weeks (-27±4% in control, -17±3% in HT-group, p

Purpose: Left Atrial Volume (LAV) is a robust index for predicting future prognosis in various clinical scenarios. However, its prognostic value in Aortic Stenosis (AS) has not been determined in a large patient population. Methods: To address this, 509 severe AS (indexed aortic valve area 50%) were enrolled from 4 Japanese cardiovascular centers. LAV at end-systole was determined by 2D biplane Simpson's method. Values were indexed to body surface area (LAVImax). All patients were followed up to determine cardiovascular death, aortic valve replacement (AVR) and Major Cardiovascular Events (MACEs). Results: Mean value of LAVImax was 45.8±18.3ml/m2. During a median of 364 days of follow up, 29 cardiac death, 217 MACEs and 175 AVR were developed. Using receiver-operating characteristic analysis, LAVImax≥52.3ml/m2 had 69% sensitivity and 72% specificity for predicting cardiac death (AUC=0.71, p

Purpose: In patients with repaired tetralogy of Fallot (ToF), right ventricular (RV) dilation and dysfunction caused by residual pulmonary regurgitation are associated with their prognosis. In contrast, left ventricular (LV) function has been focused as a novel determinant of prognosis in patients with repaired ToF. Although RV-LV interaction may cause LV dysfunction in patients with repaired ToF, the mechanism of LV dysfunction has been poorly understood. Then, we aimed to assess LV regional myocardial function through consideration of interaction with RV properties. Methods: Subclinical 32 patients with rToF (17male, 17.5yrs, range 13.5-21yrs) and 20 control subjects (9male, 11.5 yrs, range 9-13yrs) were enrolled. We examined an echocardiographic examination at the time of scheduled outpatients clinic appointment and were in sinus rhythm at the presentation. All cases were Japanese, and QRS durations were measured from the standard 12-lead electrocardiogram. RV and LV volume index (ml/m2) were measured with 3-dimensional echocardiographic system. Pulmonary regurgitation fraction (PRF) was calculated by volumetric method (RV stroke volume – LV stroke volume/RV stroke volume). Left atrium area (LA) and velocity ratio of early mitral flow to mitral ring (MV E/E') were measured for evaluation of LV diastolic function. LV longitudinal strain (LS), radial strain (RS), circumferential strain (CS) and RV-LS were assessed by 2-dimmensinal speckle tracking echocardiography. Results: QRS duration was significantly longer (114±29.7 vs 85.3±12.2, p