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OBJECTIVE Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death remains elusive. RESEARCH DESIGN AND METHODS Using the National Health Insurance Service Database, we screened subjects who underwent general health checkups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 patients with T2DM without a previous history of MI, IS, AF, and HF, we followed them until December 2018. Patients were stratified according to the magnitude of weight changes between two general health checkups: ≤ −10%, −10 to ≤ −5%, −5 to ≤5%, 5 to ≤10%, and >10%. Results During the follow-up (median 7.0 years), 32,106 cases of MI, 44,406 cases of IS, 34,953 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of −5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P < 0.0001). Similarly, the more weight loss occurred, the higher the cardiovascular risks observed (all P < 0.0001). The U-shaped associations were consistently observed in both univariate and multivariate analyses. Explorative subgroup analyses also consistently showed a U-shaped association. CONCLUSIONS Both weight loss and gain >5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM.

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.

Aims We sought to determine the risk of mental disorders in patients with hypertrophic cardiomyopathy (HCM) compared with those without HCM. Methods and results This is a retrospective propensity score-matched cohort study using nationwide population-based data from the Korean National Health Insurance Service. Overall, 4046 patients with HCM and 12138 matched individuals were followed up until the first diagnosis of mental disorders or the end of the follow up. The primary outcome was a composite of incident mood, anxiety, stress-related, or somatoform disorders. Secondary outcomes included two components of the primary outcome (i.e. mood disorders and anxiety/stress-related/somatoform disorders). During a median follow-up period of 4.1 years, the incidence rate of the primary outcome was 54.4 and 31.5/1000 person-years among the HCM and control groups, respectively, resulting in a hazard ratio (HR) of 1.719 (95% confidence interval: 1.589–1.860). Within the first month after HCM diagnosis, the HR for the primary outcome was 3.074 (2.096–4.508). Beyond 1 month, the HRs decreased, ranging from 2.281 (1.952–2.665) during 1–12 months, to 2.087 (1.831–2.380) during 12–36 months and 1.258 (1.090–1.452) after 36 months of follow up. Similar results were observed for the secondary outcomes. In sensitivity analysis, the risk of the specific categories of mental disorders, including single or recurrent depressive episodes and anxiety disorders, was also higher in patients with HCM than matched controls. Conclusion HCM was significantly associated with the risk of incident mental disorders, particularly within 1 year after HCM diagnosis, underscoring the importance of screening mental health problems, including mood and anxiety disorders, in patients with HCM.

(11)C-Pittsburgh compound B (PiB) PET/CT visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with amyloid light-chain (AL) cardiac amyloidosis (CA). However, whether (11)C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This prospective study was on a cohort of 58 consecutive patients with AL CA who underwent (11)C-PiB PET/CT. The patients were stratified into 2 groups on the basis of a visual assessment of whether there was myocardial (11)C-PiB uptake on PET/CT. The primary endpoint was 1-y overall mortality. The independent prognostic utility of (11)C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 were positive for myocardial (11)C-PiB uptake on PET/CT. Patients with myocardial (11)C-PiB PET uptake had a worse 1-y overall survival rate than those without (81.8% vs. 45.5%, P = 0.003 by log-rank test). In the multivariate analysis, positivity for myocardial (11)C-PiB uptake on PET/CT was an independent predictor of 1-y mortality (adjusted hazard ratio, 3.382; 95% CI, 1.011–11.316; P = 0.048). In analysis of 3 subgroups of patients—those with a troponin I level of at least 0.1 ng/mL, those with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of at least 1,800 pg/mL, and those with a difference of at least 180 mg/L between free light chains (the 3 commonly used biomarkers and their thresholds for staging in AL amyloidosis)—Kaplan–Meier curves showed for all 3 subgroups that patients positive for myocardial (11)C-PiB uptake on PET/CT had a worse prognosis than those who were negative. Additionally, when the results of (11)C-PiB PET/CT were added to these 3 biomarkers, the performance of 1-y mortality prediction significantly improved by net reclassification improvement (troponin I, 0.861; NT-proBNP, 0.914; difference between free light chains, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion: (11)C-PiB PET/CT is a strong independent predictor of 1-y overall mortality and provides incremental prognostic benefits beyond the 3 commonly used biomarkers of AL amyloidosis staging. Considering the recent development of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in risk stratification for patients with AL CA.

Background/Aims We evaluated changes in the ascending aorta dimension post-transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BiAV) and tricuspid aortic valve (TAV) patients. Methods Patients with severe aortic stenosis undergoing TAVR at Seoul National University Hospital were consecutively recruited. Patients with less than 12 months’ follow-up and/or with an ascending aorta size larger than 50 mm were excluded. The ascending aorta size was measured on a parasternal long axis view using transthoracic echocardiography. Results Among the 67 patients who were included (age: 76.5 ± 6.5 years; male: 52.2%; AV area: 0.67 ± 0.15 cm2), 19 (28.4%) had BiAV; 48 (71.6%) had TAV. The median (interquartile ranges) follow-up duration was 398 days (361 to 451). BiAV patients were younger (73.2 ± 7.2 vs. 77.8 ± 5.8, p = 0.008), and had lower incidences of chronic renal disease (5.3% vs. 35.4%, p = 0.014) and history of coronary intervention (15.8% vs. 50.0%, p = 0.013), than TAV patients. On pre-procedural echocardiography, the ascending aorta dimensions in BiAV patients were larger than those in TAV patients (40.5 ± 3.8 mm vs. 35.9 ± 4.2 mm, p < 0.005). The ascending aorta dimension changed minimally during follow-up; post-TAVR, the ascending aorta’s growth rate was –0.11 ± 1.9 and 0.26 ± 1.8 mm/yr in patients with BiAV and TAV, respectively (p = 0.50). Progression of the ascending aorta’s dimension postTAVR was not clinically significant in BiAV patients. Conclusions The concern about the progression of aortopathy in BiAV patients post-TAVR may not be a clinical issue. This should be confirmed in studies with a larger population and with a longer follow-up duration.

The aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS).Myocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS.Patients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation.Patients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e' 7 cm/s) and increased LV filling pressure (E/e' ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e' and higher E/septal e' ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function.Diffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.

ObjectivesPatients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery.MethodsThe retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery.ResultsDuring follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1–3) and two older groups (group 4–5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1–5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; pConclusionFive phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.

Optimizing an individual dose with careful management of adverse events (AEs) is essential in the treatment with selexipag approved for pulmonary arterial hypertension (PAH). This study aims to identify real-world practice patterns and AE characteristics of selexipag.This multicenter, longitudinal, observational study included Korean patients with PAH who initiated with selexipag and were followed up to 24 weeks. The dose-titration pattern, AE incidences by dosing and time course, recovery pattern from AEs, and relationship between doses and AE incidences were evaluated.Data for 113 patients were included in the analysis. The individual maintenance dose ranged between 200 and 3,200 µg/day. More often AEs were occurred in the titration phase than maintenance phase. There was no significant difference in AE incidences according to the distribution of titration and maintenance doses. The four most common AEs were diarrhea, headache, nausea/vomiting, and myalgia without showing a dose-dependent trend in either frequency or severity. The recovery rates were between 65.0% and 76.9% with a median time to recovery of 15-70 days (range, 2-233).Our finding that AE incidence did not increase with increasing dose of selexipag would provide supportive real-world evidence on the management of optimal dose and safety.

Background: The echocardiographic assessment of left ventricular (LV) diastolic dysfunction (LVDD) in patients with hypertrophic cardiomyopathy is complex and not well-established. We investigated whether the left atrial reservoir strain (LARS) could be used to categorize LVDD and whether this grading is predictive of heart failure (HF) events in hypertrophic cardiomyopathy. Methods: A total of 414 patients with hypertrophic cardiomyopathy (aged 58.3±12.8 years; 65.7% male) were categorized using LARS-defined LVDD (LARS-DD) grades: ≥35% (grade 0), ≥24% to Results: An increase in LARS-DD grade was associated with worse conventional echocardiographic parameters of LVDD, such as lower e′, higher E/e′ ratio, greater maximum tricuspid regurgitation velocity, and restrictive mitral inflow pattern. Higher LARS-DD grade was also associated with parameters reflecting increased LV filling pressure, such as greater LV wall thickness, greater extent of fibrosis, obstructive physiology, and decreased LV longitudinal strain. Furthermore, higher LARS-DD grade was associated with worse HF-free survival (log-rank P Conclusions: LARS can be used as a simple single or supplemental index to categorize LV diastolic function and predict HF events in hypertrophic cardiomyopathy.

Objective: Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death, remains elusive. Research Design and Methods: Using the National Database, we screened subjects who underwent general health check-ups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 T2DM patients without previous history of MI, IS, AF, and HF, we followed them up until December 2018. Patients were stratified according to the magnitude of weight changes between two general health check-ups: ≤-10%, -10 to ≤-5%, -5 to ≤5%, 5 to ≤10%, and >10%. Results: During the follow-up (median 7.0 years), 32,106 cases of MI, 44,406 cases of IS, 34,935 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of -5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P Conclusion: Both weight loss and gain beyond 5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM.

BACKGROUND AND OBJECTIVES Severe aortic stenosis (AS) with left ventricular systolic dysfunction (LVSD) is a class I indication for aortic valve replacement (AVR) but this recommendation is not well established in those at the stage of moderate AS. We investigate the clinical impact of AVR among patients with moderate AS and LVSD. METHODS From 2001 to 2017, we consecutively identified patients with moderate AS and LVSD, defined as aortic valve area 1.0-1.5 cm² and left ventricular ejection fraction

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 Conclusions Use of SGLT2i improved cardiac function in diabetic patients, regardless of the presence of HF. The improvements were more prominent in HF patients, especially in those with HFrEF. These improvements in cardiac function would contribute to the clinical benefit of SGLT2i.

Background It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis. Objectives The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition. Methods This study consecutively enrolled 41 chemotherapy-naive AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure. Results The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p Conclusions These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.

The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cmIn the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks th...

The left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) are considered as sensitive and reliable markers of cardiac remodeling and function. However, their temporal changes during optimal management of heart failure with reduced ejection fraction (HFrEF) are unknown.This study investigated the time trajectories of the LARS and LVGLS in patients with HFrEF treated with angiotensin receptor-neprilysin inhibitors, and assessed whether the LARS and LVGLS could define left heart reverse remodeling (LHRR) and reflect the treatment response and prognosis.Using a retrospective cohort of patients with HFrEF prescribed sacubitril/valsartan, we assessed the time trajectories of the LVGLS and LARS in 409 patients (1,258 echocardiograms), and investigated their association with the occurrence of cardiovascular death and hospitalization for heart failure (HHF), after the determination of LHRR, during a median follow-up of 27.1 (IQR: 18.3-36.3) months.Among patients with HFrEF prescribed sacubitril/valsartan, both the LVGLS and LARS improved over time. The improvements in the LVGLS and LARS were prominent within 6 months of sacubitril/valsartan treatment: the LVGLS improved from 10.2% (IQR: 7.9%-12.7%) to 13.9% (IQR: 10.5%-16.3%) (P 0.001), and the LARS improved from 11.4% (IQR: 8.4%-15.6%) to 15.9% (IQR: 11.5%-21.4%) (P 0.001). These improvements were larger among patients who did not experience the study outcome than in patients with events. Improvement in the LVGLS to ≥13% and LARS to ≥12.5% (ie, complete LHRR) was significantly associated with a lower risk of cardiovascular death and HHF, and this association was stronger than that of changes in other conventional echocardiographic parameters.In patients with HFrEF treated with sacubitril/valsartan, the LVGLS and LARS were improved, typically within 6 months of treatment. Complete LHRR, defined by improvement in the LVGLS and LARS, can be an indicator of treatment response and prognosis.

Aims While obesity is a well-known cardiovascular risk factor, little is known whether age has a modifying effect. The aim of this study is to determine the age-dependent associations of body mass index (BMI) with cardiovascular outcomes. Methods and results A population-based cohort of 9 278 433 Koreans without prior cardiovascular disease were followed up for the incidence of myocardial infarction (MI), heart failure (HF), and all-cause death. The effect of BMI with optimal normal weight (18.5–22.9 kg/m2) as reference was analysed according to age groups [young (20–39 years), middle-aged (40–64 years), and elderly (≥65 years)] and age decades. During 8.2 years, MI, HF, and all-cause death occurred in 65 607 (0.71%), 131 903 (1.42%), and 306 065 (3.30%), respectively. Associations between BMI and all outcomes were significantly modified by age (P-for-interaction Conclusion The impact of BMI on cardiovascular risk differs according to age. Weight loss may be recommended for younger overweight subjects, while being mildly overweight may be beneficial at old age.

Background Dementia 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. Methods In 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. Results During 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, p Conclusions This 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.

Introduction: Recent advances in nuclear molecular imaging have allowed a more specific, non-invasive approach to the diagnosis and prognostication of cardiac amyloidosis (CA). 11 C-Pittsburgh compound B positron emission tomography/computed tomography (PiB PET/CT) is one of the widely studied nuclear molecular imaging. However, it remains to be verified whether it has any independent additional prognostic value. Hypothesis: 11 C-PiB PET/CT would have independent prognostic value in patients with light chain CA (ALCA). Methods: A prospective cohort study of 58 consecutive patients with ALCA who underwent 11 C-PiB PET/CT, were stratified into 2 groups based on a myocardial 11 C-PiB uptake or not on PET/CT. The primary and secondary outcomes were all-cause death and cardiovascular death, respectively. Results: During a median 13.6 month follow-up, 29 patients died, of which 12 died from cardiovascular events. Patients with positive 11 C-PiB PET uptake had worse event-free survival from all-cause deaths (60.5% vs. 28.7%, P =0.001) and cardiovascular deaths (84.9% vs. 58.5%, P =0.001). A positive myocardial 11 C-PiB PET/CT was an independent predictor for all-cause death (adjusted hazard ratio [aHR] 4.143, 95% confidence interval [95%CI] 1.243-13.816, P =0.021) and cardiovascular death (aHR 5.598, 95%CI 1.060-29.560, P =0.043). When 11 C-PiB PET/CT was combined with troponin I and N-terminal probrain Natriuretic Peptide, the performance of prediction significantly improved by net reclassification index of 0.872 and by integrated discrimination improvement statistics of 0.177. Conclusions: 11 C-PiB PET/CT is a strong independent predictor for all-cause and cardiovascular mortality, and provides incremental prognostic benefits in patients with ALCA. Further investigations are warranted on whether PET/CT should be included in the risk stratification for the ALCA patients

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

BackgroundWe aimed to clarify the sex differences in various cardiovascular and non-cardiovascular outcomes, and to investigate whether sex differences in outcomes are affected by age in hypertrophic cardiomyopathy (HCM).MethodsA cohort of 835 patients with HCM initially evaluated during 2007–2019 were followed for a median of 6.4 years. Study outcomes were all-cause death, cardiovascular and non-cardiovascular death, sudden cardiac death (SCD)/SCD equivalent events, heart failure (HF) events, and the composite cardiovascular outcome including cardiovascular death, SCD/SCD equivalent events, admission for HF, and heart transplantation.ResultsWomen were 5 years older (women 59.9±13.5 vs. men 54.9±11.4 years), had worse dyspnea, and greater left ventricular (LV) diastolic dysfunction and obstructive physiology at presentation. Women compared to men had higher all-cause mortality and cardiovascular event rates, driven by more cardiovascular deaths and heart failure (HF) events. Conversely, non-cardiovascular mortality was not different between the sexes. Female sex was independently associated with all-cause death (HR 1.88, 95% CI 1.11–3.20) and composite cardiovascular events (HR 3.60, 95% CI 2.00–6.49), independent of age, body mass index, New York Heart Association class, SCD risk score, and LV ejection fraction. When stratified by the age of 60, sex differences were not significant at ConclusionsWomen with HCM have worse cardiovascular prognosis than men, driven by higher cardiovascular mortality and HF events. The negative impact of female sex on cardiac function and cardiovascular outcome became prominent at age ≥60 years, suggesting age-related sex differences in the prognosis of HCM.

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young individuals, largely due to ventricular arrhythmias, which may be associated with electrical disturbances from pathologic myocardial changes.The purpose of this study was to investigate electromechanical mismatches in patients with HCM and the relationship between electromechanical mismatches and life-threatening events (LTEs).We performed a retrospective review of patients (age 1-80 years) diagnosed with HCM. Electromechanical mismatch was evaluated using the electromechanical window (EMW), defined as the interval between the Q wave and aortic valve closure minus the QT interval.We enrolled 458 patients (mean age 52.4 ± 18.8 years). When the EMW of patients with HCM was compared to that of age-/sex-matched normal controls, EMW was more negative in patients with HCM than in normal controls (-51 ± 35 ms vs 7 ± 19 ms; P.001). LTEs occurred in 25 patients (5.5%). EMW was more negative in patients with LTEs than in those without (-77 ± 33 ms vs -42 ± 31 ms; P.001). The cutoff value of EMW to identify patients with LTEs was -54 ms, and the c-index of EMW was 0.726. EMW less than -54 ms, unexplained syncope, pediatric onset, and extreme left ventricular hypertrophy were significant risk factors for LTEs on multivariate analysis.EMW was more negative in patients with HCM than in healthy individuals, and profound EMW negativity was an independent risk factor for LTEs. EMW can be useful for risk stratification of SCD in patients with HCM.

Background Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown. Methods We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death. Results The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56–2.34), major bleeding (HR 0.80, 95% CI 0.32–2.03) and all-cause death (HR 1.09, 95% CI 0.73–1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76–1.47). These outcomes were not different in various subgroups analyzed. Conclusion In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.

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.

ObjectiveThe hypertrophic cardiomyopathy (HCM) risk-sudden cardiac death (SCD) calculator endorsed by the 2014 European Society of Cardiology has not been independently validated in the Asians. We aimed to investigate whether the HCM Risk-SCD calculator effectively predicts SCD in Korean HCM population.MethodsAn observational, longitudinal cohort study was performed in 730 patients with HCM from 2007 to 2017. The primary endpoint was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.ResultsDuring a follow-up period of 4288 person-years, 16 (2.2%) patients reached the primary endpoint. This validation study revealed a calibration slope of 0.892 and C-statistics of 0.718. The primary endpoint occurred in 1.1% (7/615), 4.6% (3/65) and 12.0% (6/50) of low-risk, intermediate-risk and high-risk groups, respectively. Although most patients (85.2%) without the primary endpoint were classified into the low-risk group, 7 of 11 SCD (63.6%) occurred in the low-risk group. In univariable and multivariable analysis, sex (woman) was significantly associated with the primary endpoint and emerged as independent predictor. The addition of sex to the HCM Risk-SCD calculator significantly improved the predictive value of the primary endpoint (net reclassification improvement 0.557, p=0.015).ConclusionsIn the Korean HCM population, the HCM Risk-SCD calculator had a high negative predictive value and accuracy for predicting SCD or appropriate ICD therapy, but misclassified a few patients experiencing the primary endpoint as low-risk or intermediate-risk groups.

Background Behcet’s disease (BD)-related aortic regurgitation (AR) is known to be associated with paravalvular leakage (PVL) after successful aortic valve (AV) surgery. This study aimed to determine predictors of PVL after successful AV surgery in BD patients. We retrospectively collected data of 35 patients (42.1 ± 9.1 years, 27 men) who underwent surgery for severe BD-related AR at two tertiary centers. The diagnosis was established based on echocardiographic, surgical, and/or pathological findings in conjunction with the International Study Group criteria for BD. A total of 76 cases of AV surgery in 35 patients were analyzed. Results A median follow-up duration was 8.0 years (interquartile range, 5.4–14.3 years). PVL developed in 18 patients (51.4%) within 2 years after the first surgery. Six patients who met the diagnostic criteria for BD did not develop PVL, in whom 5 patients took immunosuppressive therapy (IST). However, 4 of 9 patients (44.4%) who did not meet the diagnostic criteria developed PVL, in whom four (44.4%) patients took IST. On multivariable analysis, postoperative IST and concomitant aortic root replacement (ARR) were two independent predictors for less PVL development (HR 0.38, 95% CI 0.17–0.89, p = 0.025 for postoperative IST; HR 0.17, 95% CI 0.08–0.36, p

OBJECTIVE To investigate the diagnostic validity of coronary computed tomography angiography (cCTA) in vasospastic angina (VA) and factors associated with discrepant results between invasive coronary angiography with the ergonovine provocation test (iCAG-EPT) and cCTA. MATERIALS AND METHODS Of the 1397 patients diagnosed with VA from 2006 to 2016, 33 patients (75 lesions) with available cCTA data from within 6 months before iCAG-EPT were included. The severity of spasm (% diameter stenosis [%DS]) on iCAG-EPT and cCTA was assessed, and the difference in %DS (Δ%DS) was calculated. Δ%DS was compared after classifying the lesions according to pre-cCTA-administered sublingual nitroglycerin (SL-NG) or beta-blockers. The lesions were further categorized with %DS ≥ 50% on iCAG-EPT or cCTA defined as a significant spasm, and the diagnostic performance of cCTA on identifying significant spasm relative to iCAG-EPT was assessed. RESULTS Compared to lesions without SL-NG treatment, those with SL-NG treatment showed a higher Δ%DS (39.2% vs. 22.1%, p = 0.002). However, there was no difference in Δ%DS with or without beta-blocker treatment (35.1% vs. 32.6%, p = 0.643). The significant difference in Δ%DS associated with SL-NG was more prominent in patients who were aged < 60 years, were male, had body mass index < 25 kg/m², and had no history of hypertension, diabetes, or dyslipidemia. Based on iCAG-EPT as the reference, the per-lesion-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of cCTA for VA diagnosis were 7.5%, 94.0%, 60.0%, 47.1%, and 48.0%, respectively. CONCLUSION For patients with clinically suspected VA, confirmation with iCAG-EPT needs to be considered without completely excluding the diagnosis of VA simply based on cCTA results, although further prospective studies are required for confirmation.

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 Conclusions Persistently elevated LDL‐C and triglyceride levels were associated with atherosclerotic cardiovascular diseases risk in young Korean adults without severe hypercholesterolemia. These lipid abnormalities should be considered risk factors in young adults since their effects on lifetime atherosclerotic cardiovascular diseases risk may become more pronounced over the life course.

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 p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p Conclusions Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.

Aims We investigated the prognostic role of left ventricular global longitudinal strain (LV-GLS) and its incremental value to established risk models for predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Methods and results LV-GLS was measured with vendor-independent software at a core laboratory in a cohort of 835 patients with HCM (aged 56.3 ± 12.2 years) followed-up for a median of 6.4 years. The primary endpoint was SCD events, including appropriate defibrillator therapy, within 5 years after the initial evaluation. The secondary endpoint was a composite of SCD events, heart failure admission, heart transplantation, and all-cause mortality. Twenty (2.4%) and 85 (10.2%) patients experienced the primary and secondary endpoints, respectively. Lower absolute LV-GLS quartiles, especially those worse than the median (−15.0%), were associated with progressively higher SCD event rates (P = 0.004). LV-GLS was associated with an increased risk for the primary endpoint, independent of the LV ejection fraction, apical aneurysm, and 2014 European Society of Cardiology (ESC) risk score [adjusted hazard ratio (aHR) 1.14, 95% confidence interval (CI) 1.02–1.28] or 2011 American College of Cardiology/American Heart Association (ACC/AHA) risk factors (aHR 1.18, 95% CI 1.05–1.32). LV-GLS was also associated with a higher risk for the composite secondary endpoint (aHR 1.06, 95% CI 1.01–1.12). The addition of LV-GLS enhanced the performance of the ESC risk score (C-statistic 0.756 vs. 0.842, P = 0.007) and the 2011 ACC/AHA risk factor strategy (C-statistic 0.743 vs. 0.814, P = 0.007) for predicting SCD. Conclusion LV-GLS is an important prognosticator in patients with HCM and provides additional information to established risk stratification strategies for predicting SCD.

Background Severe tricuspid regurgitation (TR) should be intervened before the development of irreversible right ventricular (RV) dysfunction. However, current guidelines do not provide criterion related to RV systolic function to guide optimal surgical timing. We investigated the prognostic value of RV longitudinal strain in patients undergoing isolated surgery for severe functional TR. Methods and Results We enrolled 115 consecutive patients (aged 62±10 years; 23.5% men; 62.6% [n=72] with previous left‐sided valve surgery) who underwent isolated surgery for severe functional TR at 2 tertiary centers. Preoperative clinical and echocardiographic parameters, including RV free‐wall longitudinal strain (RVFWSL), were collected. The primary end point was a composite of cardiac death and unplanned readmission attributable to cardiovascular causes 5 years after surgery. Forty patients (34.8%) reached the primary end point during 333 person‐years of follow‐up. There were 11 cardiac deaths and 34 unplanned readmissions attributable to cardiovascular causes, with 5 patients experiencing both. An absolute preoperative RVFWSL P =0.011), independent of clinical risk factors, including European System for Cardiac Operative Risk Evaluation II and hemoglobin levels. Meanwhile, other conventional echocardiographic measures of RV systolic function were not significant. The addition of an absolute RVFWSL Conclusions Preoperative RVFWSL as an indicator of RV dysfunction was an independent prognosticator in patients undergoing isolated surgery for severe functional TR. Thus, preoperative RVFWSL could help determine the optimal surgical timing for severe functional TR.

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years’ median follow-up interval (range 2.0–6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p p p

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 (pppp = 0.090). Multivariable analysis demonstrated that male sex was independently associated with CAC progression rate among the entire group (p

Additional file 1: Supplementary tables and figures.

Diabetes mellitus (DM) often coexists in elderly hypertrophic cardiomyopathy (HCM) patients; however, its impact on clinical outcomes is unclear.We compared clinical outcomes according to the presence of DM in a nationwide HCM cohort.In 9,883 HCM subjects (mean age 58.5 ± 13.1, men 71.7%), 1,327 (13.4%) had DM. During follow-up (mean 5.9 ± 2.5 years), end-stage renal disease (ESRD) progression, coronary events (myocardial infarction, coronary revascularization), heart failure (HF), cardiovascular mortality, and all-cause mortality occurred in 80 (0.8%), 365 (3.7%), 1,558 (15.8%), 354 (3.6%), and 877 (8.9%) subjects, respectively. DM HCM subjects had significantly higher risks of ESRD progression (HR 3.49, 95% CI 2.20-5.54) and HF (HR 1.15, 95% CI 1.01-1.32) compared to non-DM HCM subjects, independent of age, sex, ischemic heart disease, atrial fibrillation, and other comorbidities. There was a tendency for greater risk of ESRD progression, HF, and all-cause death in subjects with more advanced stage of DM (p-for-trend 0.05 for all). Insulin-treated DM was associated with the highest risk.DM HCM subjects have higher risk of ESRD progression and HF. Considering the extended life expectancy of HCM and increasing number of elderly HCM subjects, active surveillance and management of DM-related outcomes should be highlighted.

ObjectivesRecommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population.MethodsA nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual’s PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed.ResultsA total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively (p-for-trend=0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels.ConclusionsModerate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation.

Background: There is a lack of studies investigating the heterogeneity of patients with aortic stenosis (AS). We explored whether cluster analysis identifies distinct subgroups with different prognostic significances in AS. Methods: Newly diagnosed patients with moderate or severe AS were prospectively enrolled between 2013 and 2016 (n=398, mean 71 years, 55% male). Among demographics, laboratory, and echocardiography parameters (n=32), 11 variables were selected through dimension reduction and used for unsupervised clustering. Phenotypes and causes of mortality were compared between the clusters. Results: Three clusters with markedly different features were identified. Cluster 1 (n=60) was predominantly associated with cardiac dysfunction, cluster 2 (n=86) consisted of elderly with comorbidities, especially end-stage renal disease, whereas cluster 3 (n=252) demonstrated neither cardiac dysfunction nor comorbidities. Although AS severity did not differ, there was a significant difference in adverse outcomes between the clusters during a median 2.4 years follow-up (mortality rate, 13.3% versus 19.8% versus 6.0% for cluster 1, 2, and 3, P P =0.003), whereas cluster 2 was associated with higher noncardiac mortality (adjusted hazard ratio, 3.35 [95% CI, 1.26–8.90]; P =0.015). Phenotypes and association of clusters with specific outcomes were reproduced in an independent validation cohort (n=262). Conclusions: Unsupervised cluster analysis of patients with AS revealed 3 distinct groups with different causes of death. This provides a new perspective in the categorization of patients with AS that takes into account comorbidities and extravalvular cardiac dysfunction.

Background The H2FPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the H2FPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure. Methods and Results In total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the H2FPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range 69–82). The median H2FPEF score was 4 (interquartile range 3–6). Patients with higher H2FPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the left atrium, mitral E/e’ ratio, and peak tricuspid regurgitation velocity. Peak atrial longitudinal strain of the left atrium demonstrated a significant association with the H2FPEF score, in patients without atrial fibrillation and those without atrial fibrillation. After adjustment for clinical factors and echocardiographic parameters, patients with higher H2FPEF scores had a higher risk of mortality and hospitalization for heart failure, regardless of the presence of atrial fibrillation. Conclusions The H2FPEF score reflects left atrial function in patients with HFpEF admitted for acute heart failure. This association supports the clinical usefulness of the H2FPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.

BACKGROUND Left atrial (LA) strain is a novel parameter of LA function. However, its reference value has not been established, and the determining factors for LA strain remain elusive. We aimed to present LA strain with reservoir, conduit, and contractile components and associated parameters in a large-sized group of healthy individuals. METHODS The present study was from a prospective multicenter registry in South Korea. Subjects who had no history of cardiovascular disease with adequate images were eligible for inclusion. LA reservoir, conduit, and contractile strains (LASRES, LASCD and LASCT, respectively) were measured. Left ventricular global longitudinal strain (LV GLS) and early and late diastolic strain rates (DSRe and DSRa, respectively) were also evaluated. RESULTS Among a total of 324 subjects (mean age: 49 ± 16 years, 167 females), the mean LASRES, LASCD, and LASCT values were 35.9% ± 10.6%, 21.9% ± 9.3%, and 13.9% ± 3.6%, respectively. Mean LV GLS was -20.4% ± 2.2%, and mean DSRe and DSRa were 1.6 ± 0.4 s-1 and 0.8 ± 0.3 s-1, respectively. With aging, LASRES and LASCD showed significant decreases. Factors showing independent associations with LASRES were age (B = -0.425, p < 0.001), DSRe (B = 4.706, p = 0.001), and LV GLS (B = -1.081, p < 0.001). Age (B = -0.319, p < 0.001), DSRe (B = 4.140, p = 0.002), DSRa (B = -3.409, p = 0.018), and LV GLS (B = -0.783, p < 0.001) showed associations with LASCD. With LASCT, only DSRa showed a correlation (R = 0.277, p < 0.001). CONCLUSIONS We presented LA strain in a large-sized group of healthy subjects. Age is a significant determinant of LA function. Associations of LA strain with diastolic strain rates and LV GLS reflect cardiac mechanics.

Background: Dyslipidemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We sought to investigate the risk of death and cardiovascular disease in relation to lipid components to establish evidence for primary prevention in young adults. Methods: In a nationwide cohort using the National Health Insurance claims database, we analyzed 5,688,055 statin-naïve subjects, aged 20-39 years, undergoing health check-up between 2009 and 2014. The study endpoint was a composite of clinical events, including death, myocardial infarction (MI), and stroke. We compared the incidence and the risk of clinical events according to lipid variables, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Results: During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%); 16,262 deaths (0.29%), 8,578 MIs (0.15%), and 5,967 strokes (0.10%). The risk of clinical events gradually increased with increasing TC and triglycerides, and decreasing HDL-C, with a great contribution by MI. LDL-C had a J-shaped association with the study endpoint, showing the lowest risk in LDL-C of 84-101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted HR 1.20, p Conclusions: In ‘statin-naïve’ young adults aged 20-39 years, the risk of clinical events was proportional to lipid levels; positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had the strongest and independent association with clinical events. Screening and intervention of abnormal lipid levels, particularly triglycerides, from an early age might be required.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Aims Dyslipidaemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We investigated the risks of death and cardiovascular disease in relation to each lipid component to establish evidence for primary prevention in young adults. Methods In this nationwide population-based cohort study, we analysed 5,688,055 statin-naïve subjects, aged 20–39 years, undergoing general health check-ups between 2009 and 2014. The endpoint was a composite of clinical events including death, myocardial infarction (MI), and stroke. We compared the incidence and risk of clinical events according to each lipid variable. Results During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%): 16,262 deaths (0.29%), 8578 MIs (0.15%), and 5967 strokes (0.10%). The risk of clinical events gradually increased with increasing total cholesterol (TC) and triglycerides and decreasing high-density lipoprotein cholesterol (HDL-C), largely driven by MI. Low-density lipoprotein cholesterol (LDL-C) had a J-shaped association with clinical events, showing the lowest risk for LDL-C of 84–101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted hazard ratio, 1.20; p Conclusions For statin-naïve young adults, the risk of clinical events was proportional to lipid levels, positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had an independent and the strongest association with the clinical events. Screening and intervention for abnormal lipid levels, particularly triglycerides, from an early age might be of clinical value.

Rationale: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. Objective: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. Methods and Results: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20–1.53) for total cholesterol, 1.41 (1.25–1.60) for LDL-C, 1.28 (1.11–1.47) for triglycerides, and 0.82 (0.72–0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. Conclusions: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.

Heart failure (HF) and cancer are currently two leading causes of mortality, and sometimes coexist. However, the relationship between them is not completely elucidated. We aimed to investigate whether patients with HF are predisposed to cancer development using the large Korean National Health Insurance claims database.This study included 128,441 HF patients without a history of cancer and 642,205 age- and sex-matched individuals with no history of cancer and HF between 1 January 2010 and 31 December 2015.During a median follow-up of 4.06 years, 11,808 patients from the HF group and 40,805 participants from the control were newly diagnosed with cancer (cumulative incidence, 9.2% vs. 6.4%, p 0.0001). Patients with HF presented a higher risk for cancer development compared to controls in multivariable Cox analysis [hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.61-1.68]. The increased risk was consistent for all site-specific cancers. To minimize potential surveillance bias, additional analysis was performed by eliminating participants who developed cancer within the initial 2 years of HF diagnosis (i.e. 2-year lag analysis). In the 2-year lag analysis, the higher risk of overall cancer remained significant in patients with HF (HR 1.09, 95% CI 1.05-1.13), although the association was weaker. Among the site-specific cancers, three types of cancer (lung, liver/biliary/pancreas, and hematologic malignancy) were consistently at higher risk in patients with HF. An exploratory analysis showed that patients with repeated HF hospitalization had a higher risk of cancer development compared to those without, in a pattern of stepwise increases across the three groups [controls vs. HF without re-hospitalization vs. HF with re-hospitalization ≥1; HR (95% CI), 1.00 (reference) vs. 1.55 (1.51-1.59) vs. 1.96 (1.89-2.03), respectively].Cancer incidence is higher in patients with HF than the general population. Active surveillance of coexisting malignancy needs to be considered in these patients.