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Abstract Left ventricular (LV) global longitudinal strain (LVGLS) is versatile; however, it is difficult to obtain. We evaluated the potential of an artificial intelligence (AI)-generated electrocardiography score for LVGLS estimation (ECG-GLS score) to diagnose LV systolic dysfunction and predict prognosis of patients with heart failure (HF). A convolutional neural network-based deep-learning algorithm was trained to estimate the echocardiography-derived GLS (LVGLS). ECG-GLS score performance was evaluated using data from an acute HF registry at another tertiary hospital (n = 1186). In the validation cohort, the ECG-GLS score could identify patients with impaired LVGLS (≤ 12%) (area under the receiver-operating characteristic curve [AUROC], 0.82; sensitivity, 85%; specificity, 59%). The performance of ECG-GLS in identifying patients with an LV ejection fraction (LVEF)

Abstract Background The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure. Methods We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e’ >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1–7) levels, were also assessed. Results A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (− 15.5 ± 3.1% to − 16.6 ± 2.8%, P = 0.004) compared to the placebo group (− 16.7 ± 2.7% to − 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro–B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1–7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P

Background Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET‐SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. Methods and Results We retrospectively reviewed 473 consecutive patients who underwent CPET‐SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET‐SBE parameters into a 2‐dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5‐year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow‐up (median 6.0 [1.6–10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5‐year rate 3.7% versus 7.0% versus 13.0%, respectively; log‐rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52–7.22]) and Group 3 (3.92 [1.34–11.42]) compared with Group 1. Conclusions Comprehensive evaluation using CPET‐SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

Abstract Background Diabetes mellitus (DM) is a well-established risk factor for the progression of degenerative aortic stenosis (AS). However, no study has investigated the impact of glycemic control on the rate of AS progression. We aimed to assess the association between the degree of glycemic control and the AS progression, using an electronic health record-based common data model (CDM). Methods We identified patients with mild AS (aortic valve [AV] maximal velocity [Vpeak] 2.0–3.0 m/sec) or moderate AS (Vpeak 3.0–4.0 m/sec) at baseline, and follow-up echocardiography performed at an interval of ≥ 6 months, using the CDM of a tertiary hospital database. Patients were divided into 3 groups: no DM (n = 1,027), well-controlled DM (mean glycated hemoglobin [HbA1c] 0.2 m/sec/year (adjusted OR = 1.267 per 1%-unit increase in HbA1c; 95% CI 1.106–1.453; p

Abstract We compared the efficacy and safety of third‐standard‐dose triple and third‐standard‐dose dual antihypertensive combination therapies in patients with mild to moderate hypertension. This was a phase II multicenter, randomized, double‐blind, parallel‐group trial. After a 4‐week placebo run‐in period, 245 participants were randomized to the third‐dose triple combination (ALC group; amlodipine 1.67 mg + losartan potassium 16.67 mg + chlorthalidone 4.17 mg) or third‐dose dual combination (AL group; amlodipine 1.67 mg + losartan potassium 16.67 mg, LC group; losartan potassium 16.67 mg + chlorthalidone 4.17 mg, AC group; amlodipine 1.67 mg + chlorthalidone 4.17 mg) therapy groups and followed up for 8 weeks. The mean systolic blood pressure (BP) reduction was ‐18.3 ± 13.2, ‐13.0 ± 13.3, ‐16.3 ± 12.4, and ‐13.8 ± 13.2 mmHg in the ALC, AL, LC, and AC groups, respectively. The ALC group showed significant systolic BP reduction compared to the AL and AC groups at weeks 4 (P = .010 and P = .018, respectively) and 8 (P = .017 and P = .036, respectively). At week 4, the proportion of systolic BP responders was significantly higher in the ALC group (42.6%) than in the AL (22.0%), LC (23.3%), and AC (27.1%) groups (P = .013, P = .021, and P = .045, respectively). At week 8, the proportion of systolic and diastolic BP responders was significantly higher in the ALC group (59.7%) than in the AL (39.3%) and AC (42.4%) groups (P = .022 and P = .049, respectively) at week 8. Third‐standard‐dose triple antihypertensive combination therapy demonstrated early effective BP control compared to third‐standard‐dose dual combination therapies, without increasing adverse drug reactions in patients with mild‐to‐moderate hypertension.

Abstract Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63–3.15, P

Abstract Differential diagnosis of left ventricular hypertrophy (LVH) is often obscure on echocardiography and requires numerous additional tests. We aimed to develop a deep learning algorithm to aid in the differentiation of common etiologies of LVH (i.e. hypertensive heart disease [HHD], hypertrophic cardiomyopathy [HCM], and light-chain cardiac amyloidosis [ALCA]) on echocardiographic images. Echocardiograms in 5 standard views (parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 3-chamber) were obtained from 930 subjects: 112 with HHD, 191 with HCM, 81 with ALCA and 546 normal subjects. The study population was divided into training (n = 620), validation (n = 155), and test sets (n = 155). A convolutional neural network-long short-term memory (CNN-LSTM) algorithm was constructed to independently classify the 3 diagnoses on each view, and the final diagnosis was made by an aggregate network based on the simultaneously predicted probabilities of HCM, HCM, and ALCA. Diagnostic performance of the algorithm was evaluated by the area under the receiver operating characteristic curve (AUC), and accuracy was evaluated by the confusion matrix. The deep learning algorithm was trained and verified using the training and validation sets, respectively. In the test set, the average AUC across the five standard views was 0.962, 0.982 and 0.996 for HHD, HCM and CA, respectively. The overall diagnostic accuracy was significantly higher for the deep learning algorithm (92.3%) than for echocardiography specialists (80.0% and 80.6%). In the present study, we developed a deep learning algorithm for the differential diagnosis of 3 common LVH etiologies (HHD, HCM and ALCA) by applying a hybrid CNN-LSTM model and aggregate network to standard echocardiographic images. The high diagnostic performance of our deep learning algorithm suggests that the use of deep learning can improve the diagnostic process in patients with LVH.

Abstract Aims Some patients with apparent heart failure (HF) have an ejection fraction (EF) ≥ 50% and elevated levels of natriuretic peptides (NPs), but no significant diastolic dysfunction. Among these, some may have HF, others may not. Myocardial strain is an excellent prognostic factor. Methods and results Among 4312 consecutive patients with acute HF from three tertiary hospitals, we included 355 patients with EF of ≥50% and elevated levels of NPs, without significant diastolic dysfunction. Patients were classified as having impaired global longitudinal strain (GLS

Abstract Low bone mineral density (BMD) is associated with higher risk of atherosclerotic cardiovascular disease (ASCVD) in women. We investigated whether the association between low BMD and ASCVD differs according to the age at ASCVD occurrence. We retrospectively analyzed 7932 women aged 50–65 years who underwent dual-energy X-ray absorptiometry. ASCVD was defined as a composite of ASCVD death, myocardial infarction, and ischemic stroke. When we classified participants into no event (n = 7803), early ASCVD (

Abstract Insufficient evidence is available comparing mortality and cause of death between general hypertrophic cardiomyopathy (HCM) and general non-HCM populations. We aimed to investigate how causes of death and mortality differ in subjects with and without HCM. Using the National Health Insurance Service database from 2009 to 2016, individuals who underwent health check-up(s) with or without a history of HCM were identified. Participants in the HCM group were matched at a 1:1 ratio with those in the non-HCM group using propensity scores calculated from the baseline covariates. Mortality rates and risks were compared between the groups. In total, 14,858 participants (7,429 each in the HCM and non-HCM groups) were followed up over a mean 4.4 ± 2.2 years (mean age, 61.0 years; male proportion, 66.8%). Compared to the non-HCM group, the HCM group showed a higher risk of all-cause and HCM-related mortality and a similar risk for non-cardiovascular mortality (hazard ratio [95% confidence interval] 1.57 [1.38–1.78], 2.71 [1.92–3.83], and 1.04 [0.88–1.23], respectively). The sensitivity analyses consistently showed that the HCM group showed higher risks of all-cause and HCM-related mortality than the non-HCM group. The female participants with HCM were associated with an increasing trend of the risks of all-cause mortality but not HCM-related mortality compared to their male counterparts (p for interaction

Abstract Aims Not all patients with heart failure with reduced ejection fraction (HFrEF) benefit equally from beta‐blockers. Previous studies suggest that myocardial strain that reflects myocardial deformation may have a better prognostic value than the left ventricular ejection fraction. We aimed to evaluate the differential effect of beta‐blockers according to the global longitudinal strain (GLS) in patients with HFrEF. Methods and results Of the 4312 patients in the Strain for Risk Assessment and Therapeutic Strategies in Patients with Acute Heart Failure registry, we included 2126 HFrEF patients whose data on beta‐blocker use and GLS were available. Patients were categorized into two groups: one group of patients had GLS ≥ 10%, and the other group had GLS 0.05). Conclusions Beta‐blocker use appears to be associated with improved survival in patients with HFrEF and GLS

Abstract Aims Contemporary heart failure (HF) classification based on left ventricular (LV) ejection fraction is limited for comprehensive assessment of LV function. We aimed to validate the feasibility of the contraction–relaxation coupling index (CRC) as a novel predictor for clinical outcomes in patients with acute HF. Methods and results A total of 3266 consecutive patients (median age: 74 years, 53% male) with acute HF were included. CRC was defined as the ratio of end‐diastolic elastance (LV end‐diastolic pressure/stroke volume) to end‐systolic elastance (LV end‐systolic pressure/end‐systolic volume). The risk for 1 year composite endpoint of all‐cause mortality or hospitalization for HF (primary outcome) was compared after group categorization using CRC tertiles (Tertile 1: CRC ≤ 0.17, Tertile 2: 0.17

Background Previous studies have demonstrated that 2‐dimensional (2D) global longitudinal strain (GLS) is associated with cardiovascular outcomes in patients with left bundle‐branch block. However, the predictive value of 3‐dimensional (3D) speckle‐tracking echocardiography has not yet been investigated in these patients. Methods and Results The authors retrospectively identified 290 patients with left bundle‐branch block who underwent echocardiography more than twice. Using speckle‐tracking echocardiography, 2D‐GLS, 3D‐GLS, 3D‐global circumferential strain, 3D global radial strain, and 3D global area strain were acquired. The association between 2D and 3D strains and the follow‐up left ventricular (LV) ejection fraction (LVEF) was analyzed. The study population was divided into 2 sets: a group with preserved LVEF (baseline LVEF ≥40%) and a group with reduced LVEF (baseline LVEF

Abstract Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death and morbidity worldwide. This randomized controlled, single-center, open-label trial tested the impact of a mobile health (mHealth) service tool optimized for ASCVD patient care. Patients with clinical ASCVD were enrolled and randomly assigned to the intervention or control group. Participants in the intervention group were provided with a smartphone application named HEART4U, while a dedicated interface integrated into the electronic healthcare record system was provided to the treating physicians. A total of 666 patients with ASCVD were enrolled, with 333 patients in each group. The estimated baseline 10-year risk of cardiovascular disease was 9.5% and 10.8% in the intervention and control groups, respectively, as assessed by the pooled cohort risk equations. The primary study endpoint was the change in the estimated risk at six months. The estimated risk increased by 1.3% and 1.1%, respectively, which did not differ significantly (P = 0.821). None of the secondary study endpoints showed significant differences between the groups. A post-hoc subgroup analysis showed the benefit was greater if a participant in the intervention group accessed the application more frequently. The present study demonstrated no significant benefits associated with the use of the mHealth tool in terms of the predefined study endpoints in stable patients with ASCVD. However, it also suggested that motivating patients to use the mHealth tool more frequently may lead to greater clinical benefit. Better design with a positive user experience needs to be considered for developing future mHealth tools for ASCVD patient care. Trial Registration: ClinicalTrials.gov NCT03392259

Abstract Aims The benefit of statins in patients with heart failure (HF) remains controversial and the mechanism of action is largely speculative. We investigated the determinants of the survival benefit associated with statins in HF patients. Methods and results We enrolled 1680 acute HF patients receiving statins and 2157 patients not receiving statins admitted between 2009 and 2016. The left ventricular (LV) global longitudinal strain (GLS) was assessed as a measure of myocardial contractility. The primary outcome was 5 year all‐cause mortality. Statin therapy was independently associated with improved survival in patients with HF with preserved ejection fraction (HFpEF) [adjusted hazard ratio (HR) 0.781, 95% confidence interval (CI) 0.621–0.981, P = 0.034], but not in those with HF with reduced EF (HFrEF) (adjusted HR 0.881, 95% CI 0.712–1.090, P = 0.244). Mortality reduction associated with statin therapy was significant in patients with ischaemic HF (adjusted HR 0.775, 95% CI 0.607–0.989, P = 0.040), but not in those with non‐ischaemic HF (adjusted HR 0.895, 95% CI 0.734–1.092, P = 0.275). The relative magnitude of survival benefit with statin therapy increased as LV‐EF and LV‐GLS increased, with a steeper dose–response relationship in patients with ischaemic HF. In the subgroup of patients with ischaemic HF, survival benefit with statin therapy was confined to those ≤75 years of age. Conclusions Our study suggests that the survival benefit of statins is confined to patients with HFpEF and those with ischaemic HF. Myocardial contractility may modulate the prognostic effects of statins in HF patients, particularly when the aetiology is ischaemic rather than non‐ischaemic.

BackgroundLeft ventricular (LV) hypertrophy (LVH) in patients with hypertension is a significant risk factor for cardiovascular mortality and morbidity. However, the prognostic implication of LVH regression after antihypertensive therapy has not been clearly investigated.MethodsPatients who underwent echocardiography at the time of the diagnosis of hypertension and repeated echocardiography at an interval of 6–18 months were retrospectively identified. LVH was defined as LV mass index (LVMI) >115 g/m2 (men) and >95 g/m2 (women). LVH regression was defined as LVH at initial echocardiography with normal geometry or concentric LV remodeling at follow-up echocardiography. Cardiovascular mortality, hospitalization for heart failure (HHF), coronary revascularization, stroke, and aortic events were analyzed according to changes in LVMI and geometry.ResultsOf 1,872 patients, 44.7% (n = 837) had LVH at the time of diagnosis; among these, 30.7% showed LVH regression. The reduction in LVMI was associated with the reduction in BP, especially in those with LVH at baseline. During follow up (median, 50.4 months; interquartile range, 24.9–103.2 months), 68 patients died of cardiovascular causes, 127 had HHF, and 162 had vascular events (coronary revascularization, stroke, and aortic events). Persistent or newly developed LVH during antihypertensive therapy was a significant predictor of cardiovascular mortality and events, especially HHF. On multivariable analysis, women, diabetes, atrial fibrillation, coronary artery disease, larger LVMI and end-diastolic dimension, and less reduction in systolic BP were associated with persistent or newly developed LVH.ConclusionLVH regression in patients with hypertension is associated with a reduction in cardiovascular events and can be used as a prognostic marker.

Background Heart failure (HF) involves dysfunction of the left ventricle (LV) as well as left atrium and right ventricle. We characterized mechanical phenotypes of HF using 3‐chamber strain echocardiography and compared their clinical outcomes. Methods and Results We retrospectively analyzed 3574 patients (median age, 74 years; male 52.8%) with acute HF who underwent 3‐chamber strain echocardiography. Patients were classified as with LV, left atrium, or right ventricle myopathy if their corresponding strain values (LV global longitudinal strain, left atrium reservoir strain, and right ventricle global longitudinal strain) were lower than median cutoffs, respectively. The mechanical phenotypes of individual patients were characterized according to the combined myopathy. The primary outcome was a composite end point of 5‐year all‐cause mortality and HF hospitalization. During follow‐up (median, 25.8 months), the primary outcome occurred in 1877 (52.5%) patients. Three‐chamber strain values were independent predictors for the primary outcome. An incremental trend was observed for the primary outcome, along with the increasing numbers of combined myopathy. Each mechanical phenotype exhibited an increased risk of the primary outcome, with the highest risk observed in patients with 3‐chamber myopathy (hazard ratio, 1.67 [95% CI, 1.42–1.96]). The prognostic significance of the mechanical phenotypes was feasible across the conventional HF subtypes stratified by LV ejection fraction. In HF with preserved ejection fraction, the presence of left atrium and right ventricle myopathy significantly increased the primary outcome, regardless of combined left ventricle myopathy. Conclusions Assessment of 3‐chamber strain in HF enables characterization of distinctive mechanical phenotypes, which provides an independent prognostic value that may support long‐term risk stratification.

Abstract Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium–glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e′ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.

Background Apart from nondippers’ impact on cardiovascular events, the prevalence of isolated nocturnal hypertension (INH) and its consequences on both the heart and brain were not clearly investigated in the general population. Methods and Results The participants underwent ambulatory blood pressure monitoring evaluations for arterial stiffness, echocardiography, and brain magnetic resonance imaging. They were grouped into normotension, INH, and overt diurnal hypertension, based on ambulatory blood pressure monitoring and history of antihypertensive treatment. White matter hyperintensity, arterial stiffness, and echocardiographic parameters were compared. Of the 1734 participants, there were 475 (27.4%) subjects with normotension, 314 with INH (18.1%), and 945 with overt diurnal hypertension (54.5%). Prevalence of INH was not different between sex or age. Of INH, 71.3% (n=224) was caused by elevated diastolic blood pressure. After multivariable adjustment, INH showed higher pulse wave velocity (P

Abstract Aims Despite well‐established benefits of sacubitril/valsartan for cardiac reverse remodelling and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF), there are some patients with limited therapeutic response, even with optimal therapy. We assessed the treatment response to sacubitril/valsartan in patients with HFrEF, focusing on the association between reverse remodelling and the prognosis. Methods and results Using a retrospective cohort of consecutive patients with HFrEF treated with sacubitril/valsartan, we compared the time trajectory of cardiac function in 415 patients (1258 echocardiograms), according to the occurrence of cardiovascular death and hospitalization for HF during a median follow‐up of 19.1 (interquartile range, 10.9–27.6) months. A higher sacubitril/valsartan dose was associated with a better prognosis, whereas advanced age, diabetes, left ventricular (LV) hypertrophy, left atrial enlargement, and pulmonary hypertension were associated with a worse prognosis. Patients without an event (n = 337; 81.2%) showed LV reverse remodelling (LV ejection fraction ≥45% or LV end‐systolic volume reduction by 15% from baseline), which was typically observed within 6 months of sacubitril/valsartan treatment. Reverse remodelling achievement was significantly associated with a better prognosis. However, patients without reverse remodelling had a worse prognosis, as poor as that in patients with HFrEF not treated with sacubitril/valsartan. Conclusions In patients with HFrEF treated with sacubitril/valsartan, LV reverse remodelling reflects the treatment response and predicts the prognosis, whereas a lack of reverse remodelling indicates the lack of treatment benefits. Prediction and assessment of reverse remodelling may facilitate the selection of patients with greater benefits by sacubitril/valsartan.

Abstract We aimed to investigate the sex differences in associations of diabetes mellitus (DM) with echocardiographic phenotypes and clinical outcomes of heart failure (HF). We studied 4,180 patients admitted for acute HF between 2009 and 2016 (median follow-up, 31.7 months) whose left ventricular global longitudinal strain (LV-GLS) data were available. Patients were compared by sex and DM. Structural equation model (SEM) analysis was performed to evaluate the moderating effects of two causal paths, via ischemic heart disease (IHD) and LV-GLS, linking DM with mortality. Compared to non-diabetic women, diabetic women had significantly lower LV-GLS (11.3% versus 10.1%, p

Abstract Background Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD. Methods A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing 95 g/m2 in women and > 115 g/m2 in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality. Results A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p

Abstract Background The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity. Methods We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT. Results Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P

Abstract Background The effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiac function are not fully understood. We investigated the changes in cardiac function in diabetic patients according to the presence and types of heart failure (HF). Methods We retrospectively identified 202 diabetic patients who underwent echocardiography before, and 6 to 24 months after the initiation of SGLT2i. After propensity score matching with diabetic patients without SGLT2i, the study population (n = 304) were categorized into group 1 (without HF nor SGLT2i; n = 76), group 2 (without HF and received SGLT2i; n = 78), group 3 (with HF but without SGLT2i; n = 76), and group 4 (with HF and received SGLT2i; n = 74). Changes in echocardiographic parameters were compared between these 4 groups, and between HF patients with reduced versus preserved ejection fraction (EF). Results After a median 13 months of follow-up, HF patients with SGLT2i showed a significant decrease in left ventricular end-diastolic dimension (LV-EDD; from 57.4 mm [50.0–64.9] to 53.0 mm [48.0–60.0]; p

BackgroundDementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated.MethodsIn a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) between groups.ResultsDuring follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26-1.84, pConclusionsThis is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality.

BackgroundCardiovascular and renal benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been clearly demonstrated. However, studies comparing the effects of dapagliflozin and empagliflozin are scarce. In addition, relatively few studies have analyzed the effects of SGLT2i in diabetic patients without established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF), and current guidelines recommend SGLT2i and other antidiabetic drugs equally in this population. Therefore, we aimed to compare the clinical outcomes between dapagliflozin, empagliflozin, and dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with type 2 diabetes without prior ASCVD, CKD, or HF.MethodsUsing a propensity-score matching method, we retrospectively analyzed 921 patients treated with dapagliflozin, 921 patients treated with empagliflozin, and 1842 patients treated with DPP4i (control group). Study outcomes comprised composite coronary events (acute coronary syndrome and coronary revascularization), composite ischemic events (coronary events and stroke), and composite heart failure and renal events.ResultsDuring follow up (median, 43.4 months), the incidence of composite coronary events was significantly lower in the SGLT2i groups than in the control group, and the incidence of composite ischemic events was lower in the dapagliflozin group than in the control group. Dapagliflozin and empagliflozin both demonstrated significant benefits in terms of HF and renal outcomes, supported by renoprotective effects, as assessed by the change in glomerular filtration rate. At 24-36 months of treatment, the empagliflozin group had higher low-density lipoprotein cholesterol levels, and lower glycated hemoglobin levels, compared to those in the dapagliflozin and control groups.ConclusionSGLT2i use was associated with a significantly reduced risk of ASCVD, HF hospitalization, and renal events, compared to that with DPP4i use among diabetic patients without prior ASCVD, CKD, or HF. There were no significant differences in clinical outcomes between dapagliflozin and empagliflozin, supporting a SGLT2i class effect.

Background Stroke is a major comorbidity in patients with heart failure (HF), especially in those with decreased left atrial (LA) function, and thus, identifying patients highly at risk of stroke can prevent its occurrence. We evaluated the predictive value of global longitudinal strain of LA (LAGLS) in patients with acute HF and sinus rhythm. Methods and Results In this retrospective study, 2461 patients (53.3% men, 69.7±14.4 years old) with sinus rhythm and LAGLS among 4312 consecutive patients with acute HF from 3 tertiary hospitals were included. HF phenotypes were defined as HF with reduced ejection fraction (EF) (left ventricular EF ≤40%), HF with midrange EF (40%

Background Identifying predictive markers for future atherosclerotic cardiovascular diseases may be helpful to motivate young adults to promote healthy lifestyle. We sought to determine the association between persistently elevated low‐density lipoprotein‐cholesterol (LDL‐C) and/or triglyceride levels and the atherosclerotic cardiovascular diseases risks in young adults. Methods and Results We conducted a nationwide population‐based cohort study of 1 887 853 statin‐naive adults aged 20 to 39 years, with LDL‐C

Abstract Background Limited data exists regarding healthcare utilization, medical expenses, and prognosis of pulmonary hypertension (PH) according to the World Health Organization (WHO) classification. We aimed to investigate mortality risk, healthcare utilization and medical expenditure in patients with PH across the five diagnostic subgroups. Methods We identified 2185 patients with PH, defined as peak tricuspid regurgitation velocity > 3.4 m/sec, among the consecutive patients referred for echocardiography between 2009 and 2015. Using diagnostic codes, medical records, and echocardiographic findings, the enrolled patients were classified according to the five subgroups by WHO classification. Healthcare utilization, costs, and all-cause mortality were assessed. Results Diagnostic subgroups of PH demonstrated significantly different clinical features. During a median of 32.4 months (interquartile range, 16.2–57.8), 749 patients (34.3%) died. Mortality risk was the lowest in group II (left heart disease) and highest in group III (chronic lung disease). The etiologies of pulmonary arterial hypertension (PAH) had significant influence on the mortality risk in group I, showing the worst prognosis in PAH associated with connective tissue disease. Medical expenditure and healthcare utilization were different between the PH subgroups: groups II and V had more hospitalizations and medical expenses than other groups. Regardless of PH subgroups, the severity of PH was associated with higher mortality risk, more healthcare utilization and medical expenditure. Conclusions Significant differences in clinical features and prognostic profiles between PH subgroups reflect the differences in pathophysiology and clinical consequences. Our findings highlight the importance of comprehensive understanding of PH according to the etiology and its severity.

Abstract Background Adults with unoperated congenitally corrected transposition of the great arteries are rare but form a distinct group among adults with congenital heart disease. Patients with congenitally corrected transposition of the great arteries often have one or more associated cardiac anomalies that dictate the need for, and timing of, surgical intervention in childhood. However, in a proportion of patients, the hemodynamics does not require surgical attention during childhood, and, in some patients, a correct diagnosis is not established until adulthood. Here we report an adult case of unoperated congenitally corrected transposition of the great arteries with a large ventricular septal defect and probable pulmonary arterial hypertension. Case presentation Our patient was a 46-year-old Korean man. Transthoracic echocardiography and cardiac catheterization demonstrated hemodynamically balanced ventricles with a non-regurgitant systemic atrioventricular valve, normal pulmonary arterial pressure, and a reasonable difference between the oxygen saturation values of the aorta and pulmonary trunk, even with the presence of a large ventricular septal defect. Further morphological assessments using cardiac computed tomography and three-dimensional modeling/printing of his heart revealed that the mitral valve was straddling over the posteriorly positioned ventricular septal defect, which could explain the functional and anatomical subvalvular pulmonary stenosis and a small amount of shunt flow through the large ventricular septal defect. We interpreted this combination of cardiac defects as able to sustain his stable cardiac function. Thus, we decided to maintain his unoperated status. Conclusion A detailed anatomical understanding based on transthoracic echocardiography, cardiac computed tomography, and three-dimensional printing can justify a decision to not operate in cases of congenitally corrected transposition of the great arteries with hemodynamically balanced pulmonary stenosis and a ventricular septal defect, as observed in the present case.

Even with increasing awareness of sex-related differences in atherosclerotic cardiovascular disease (ASCVD), it remains unclear whether the progression of coronary atherosclerosis differs between women and men. We sought to compare coronary artery calcium (CAC) progression between women and men. From a retrospective, multicentre registry of consecutive asymptomatic individuals who underwent CAC scoring, we identified 9,675 men and 1,709 women with follow-up CAC scoring. At baseline, men were more likely to have a CAC score >0 than were women (47.8% vs. 28.6%). The probability of CAC progression at 5 years, defined as [√CAC score (follow-up)-√CAC score (baseline)] ≥2.5, was 47.4% in men and 29.7% in women (p

Background Many patients with heart failure (HF) experience changes in left ventricular ejection fraction (LVEF) during follow‐up. We sought to evaluate the predictors and outcomes of different HF phenotypes according to longitudinal changes in EF. Methods and Results A total of 2104 patients with acute HF underwent echocardiography at baseline and follow‐up. Global longitudinal strain was measured at index admission. HF phenotypes were defined as persistent HF with reduced EF (persistent HFrEF, LVEF ≤40% at baseline and follow‐up), heart failure with improved ejection fraction (LVEF≤40% at baseline and improved to >40% at follow‐up), heart failure with declined ejection fraction (LVEF>40% at baseline and declined to ≤40% at follow up), and persistent HF with preserved EF (persistent HFpEF, LVEF>40% at baseline and follow‐up). Overall, 1130 patients had HFrEF at baseline; during follow‐up, 54.2% and 46.8% had persistent HFrEF and heart failure with improved ejection fraction, respectively. Among 975 patients with HFpEF at baseline, 89.5% and 10.5% had persistent HFpEF and heart failure with declined ejection fraction at follow‐up, respectively. The 5‐year all‐cause mortality rates were 43.1%, 33.1%, 24%, and 17% for heart failure with declined ejection fraction, persistent HFrEF, persistent HFpEF, and heart failure with improved ejection fraction, respectively (global log‐rank P

ObjectivesImpact of sex and myocardial function on the obesity paradox in heart failure (HF) is unknown. We explored whether sex, myocardial function, and left ventricular (LV) geometry explains the protective association of body mass index (BMI) with mortality, and investigated whether metabolic health status affects this association.DesignA multicentre cohort study with patients with acute HF admitted from January 2009 to December 2016 with a median follow-up of 33.7 months.SettingThree tertiary hospitals.ParticipantsA total of 2021 overweight-to-obese (OW) and 1543 normal-weight (NW) patients with acute HF.MeasurementsThe primary outcome was all-cause mortality. Patients were categorised as either OW (BMI≥23kg/m2) or NW (BMI10.1%) or elderly patients (≥75 years). In men, this association was found in all subgroups without significant interaction. Metabolically healthy obese patients had better survival than metabolically unhealthy obese patients (log-rank p

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications.

BackgroundPulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes.MethodsWe enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened.ResultsAmong 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; pConclusionThe prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers.Clinical trial registrationClinicaltrials.gov NCT01054105.

Abstract Background The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS). Methods/design The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease. Discussion In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy. Trial registration ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Abstract Background Previous studies suggested that phosphodiesterase 5 inhibitors (PDE5i) have a beneficial effect in patients with heart failure (HF), although the results were inconsistent. We performed a meta-analysis to evaluate the effect of PDE5i in HF patients, and investigated the relationship between PDE5i effects and pulmonary hemodynamics. Method We searched PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) that compared PDE5i with placebo in HF with reduced ejection fraction (HFrEF) or HF with preserved EF (HFpEF). PDE5i effects were interpolated according to baseline pulmonary arterial pressure (PAP) or according to changes in PAP after PDE5i treatment. Results Thirteen RCTs enrolling 898 HF patients, and two sub-analysis studies with different study outcomes, were included in the meta-analysis. Among patients with HFrEF, PDE5i improved peak VO2 (mean difference [MD], 3.76 mL/min/kg; 95% confidence interval [CI], 3.27 to 4.25; P

Background Few studies have shown that right ventricular (RV) function is independently related to adverse events regardless of left ventricular (LV) function in heart failure. We evaluated the prognostic value of global longitudinal strain (GLS) of both ventricles in patients with acute heart failure. Methods and Results We measured biventricular strains in 1824 randomly selected patients (973 men, aged 70±14 years) from a strain registry. A total of 799 patients (43.8%) died during the median follow‐up duration of 31.7 months. In univariate analysis, LVGLS and RVGLS were significantly associated with all‐cause mortality. We classified them into 4 strain groups according to LVGLS (≥9%) and RVGLS (≥12%). On Cox proportional hazards analysis, group 4 (

[This corrects the article DOI: 10.1371/journal.pone.0174160.].

We aimed to evaluate the predictive power of longitudinal and circumferential fibers according to left ventricular ejection fraction (LVEF) in successfully reperfused acute ST elevation myocardial infarction (STEMI) patients.Total 691 patients (age 59±13, 20% female) underwent clinical evaluation and conventional and strain echocardiography (Global longitudinal strain (GLS), global circumferential strain (GCS)). The clinical outcome was defined as the composite of death, hospitalization for heart failure, non-fatal myocardial infarction, and ventricular arrhythmia.During a follow-up of 39±19 months, there were 47 (6.8%) clinical events. In multivariate Cox models adjusted clinical risk factors, age (HR 1.08, p = 0.001) and GLS (HR 1.37, p = 0.001) were independent predictors. The addition of GLS resulted in significant incremental improvement in the predictive value on LVEF (χ2 = 31.8→45.8, p50%), GLS, GCS and LVEF did not show significant predictive power.GLS is a most powerful predictor of outcome in successfully reperfused STEMI patients, especially with depressed LV dysfunction, although GCS and LVEF lost their predictive power for the patients with significantly depressed LV function. However, GLS did not predict outcome for the patients with preserved LVEF (>50%).

Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT.A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies).During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p

Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM). Although left atrial (LA) remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men) were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men) and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men). The LA diameter, volume, and mechanical function, including global strain (ε), were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV) wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE) were evaluated with cardiac magnetic resonance imaging.HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax) of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance imaging.