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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.

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.

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...

BackgroundProton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs.MethodsAmong patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke.ResultsDuring a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation.ConclusionIn patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

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

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.

Although percutaneous coronary intervention (PCI) has been the mainstay of revascularization strategy for significant coronary artery disease, future cancer risk after PCI has never been explored. We aimed to investigate the risk of incident cancer in patients undergoing PCI for the first time.We studied 125,613 patients who underwent the first PCI between 2010 and 2015 without a prior history of cancer. For comparison, we selected 628,065 age- and sex-matched controls without any history of cancer or PCI who completed the assigned national health examination during the same period.During a median 4.56 years (interquartile range, 3.06-6.13 years), 8528 patients from the PCI group and 40,166 controls were newly diagnosed with cancer (incidence rate, 15.1 vs. 13.9 per 1000 person-years, p 0.0001). Patients undergoing PCI presented a higher risk for cancer development than the controls in multivariable Cox analysis (adjusted HR [aHR] 1.06, 95% CI 1.04-1.09, p 0.0001). To minimize potential surveillance bias, we performed 1-year lag analysis by eliminating participants who developed cancer within 1 year from the PCI. In this analysis, the increased risk of overall cancer in the PCI group became insignificant (aHR 1.02, 95% CI 0.99-1.05, p = 0.2017). Regarding site-specific cancers, however, the risk of lung and hematologic malignancies remained higher and the risk of gastrointestinal, liver/biliary/pancreas, thyroid, and breast cancers remained lower in the PCI group.Differential future cancer risks were observed in patients undergoing PCI. The results suggest that specialized surveillance strategy might be warranted for this expanding population.

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.

Although proteinuria is a well-known risk factor for cardiovascular disease, its relationship with the progression of aortic stenosis (AS) has not been established. Our aim was to investigate the relationship between proteinuria (detected by urine dipstick test) and AS progression (assessed by the annualized reduction rate of aortic valve area [AVA]). A total of 460 patients with mild to moderate AS (defined by a peak velocity of 2.0–4.0 m/s) without end-stage renal disease who underwent two echocardiograms at least 3 months apart were included. The progression of AS was significantly faster in patients with proteinuria than those without (108 patients vs. 352 patients; annualized reduction rate of AVA, − 7.7 ± 13.5% vs. − 4.5 ± 11.6%; p = 0.017). The relationship between the presence of proteinuria and the accelerated progression of AS was significant among patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (− 11.0 ± 17.5% vs. − 4.2 ± 10.0%; p

Isolated cardiac sarcoidosis is a generally accepted disease condition, and the low yield of endomyocardial biopsy because of patchy involvement is also well known. However, current guidelines still require histologic confirmation of granuloma for the diagnosis of cardiac sarcoidosis, either in myocardial or extra-cardiac tissues. Therefore, only a presumptive diagnosis of chronic multifocal myocarditis of unknown origin can be made in a large number of patients in whom the only considerable diagnosis is cardiac sarcoidosis based on current knowledge. Even if these patients are treated with the same treatment scheme as that for cardiac sarcoidosis, which may not cause harm in the absence of a definite diagnosis, the true spectrum of cardiac sarcoidosis could not be determined for deciding the optimal treatment strategy. In addition, the current recommendations for dose, duration of initial steroid therapy, and treatment in patients who did not respond to initial steroid therapy are not easy to follow in real-world practice. We would like to propose a scoring system for the diagnosis of cardiac sarcoidosis and suggest our adoption or modification of the diverse current recommendations.

We investigated whether global longitudinal strain (GLS) is a better predictor of clinical events after surgery for mitral regurgitation (MR) than conventional parameters.The optimal timing for surgery is guided by left ventricular (LV) dimension or left ventricular ejection fraction (LVEF), even though normal LVEF can mask depressed LV systolic function in severe mitral MR.From 2006 to 2016, 506 patients (age 58.5 ± 13.7 years, 54.3% male) with severe primary MR who underwent mitral valve surgery were included. We measured GLS and global circumferential strain. Cardiac events included admission for worsening heart failure (HF), reoperation for failure of MV surgery, and cardiac death.During a median follow-up period of 3.5 years, 56 (11.1%) patients died, 41 (8.1%) were hospitalized for HF, and 10 (2.0%) underwent reoperation. In univariate analysis, LVEF, atrial fibrillation, left atrial dimension, age, previous ischemia, concomitant coronary artery bypass graft, and both GLS and global circumferential strain were predictive of cardiac events. On multivariate Cox models, age (hazard ratio [HR]: 1.429, 95% confidence interval [CI]: 1.116 to 1.831; p = 0.005), left atrial dimension (HR: 1.034, 95% CI: 1.006 to 1.063; p = 0.019) and GLS (HR: 1.229, 95% CI: 1.135 to 1.331; p 0.001) were independent predictors of cardiac events. In subgroup analysis, LV GLS was a significant predictor of cardiac outcome, regardless of the presence of LV dysfunction, the presence of atrial fibrillation, and the type of surgery. Impaired GLS was associated with all-cause mortality (HR: 1.068, 95% CI: 1.003 to 1.136; p = 0.040).GLS appears to be a better predictor of cardiac events all-cause death than conventional parameters. Measuring preoperative GLS is helpful to predict post-operative outcome and determine optimal timing for surgery in patients with severe primary MR.

Background While coronary computed tomography angiography (CCTA) provides comprehensive anatomic evaluation of coronary artery disease (CAD) with prognostic implications, clinically, the focus is usually placed on presence or absence of functionally significant CAD. Herein, we aimed to suggest a new risk stratification strategy using CCTA in patients with anatomic CAD but without myocardial ischemia on single-photon emission computed tomography (SPECT). Methods Consecutive patients (n = 798) with CAD on CCTA who underwent SPECT for evaluation of myocardial ischemia were retrospectively evaluated. The primary outcome was the occurrence of adverse cardiac events, including cardiac death, nonfatal myocardial infarction, unstable angina, and late revascularization. Results Of the enrolled patients, 542 (68%) showed no perfusion defect (PD) on SPECT. During the follow-up (median, 22.6 months), adverse cardiac events occurred in 23 patients without PD (4.6%). Presence of plaque in ≥4 coronary segments, plaque in the left main or proximal left anterior descending coronary artery, and partially calcified plaque presence were independent predictors of adverse events. When we defined the CCTA score based on these 3 predictors (0–3 points), the annualized event rates increased with increasing CCTA scores. Patients with a CCTA score of 3 were associated with a 23-fold risk increase (adjusted HR 23.18; p = 0.003) and showed unfavorable event-free survival, comparable to those with PD on SPECT (p = 0.191). Conclusion Anatomic CAD patients without evidence of myocardial ischemia on SPECT but with high-risk characteristics on CCTA showed unfavorable outcomes, comparable to those with PD. CCTA allows further risk stratification even in patients with negative SPECT findings.

The aim of this study was to evaluate whether native T1 value of the myocardium on cardiac magnetic resonance (CMR) could predict clinical events in patients with significant aortic stenosis (AS).Although previous studies have demonstrated the prognostic value of focal fibrosis using late gadolinium enhancement (LGE) by CMR in AS patients, the prognostic implication of diffuse myocardial fibrosis by noninvasive imaging remains unknown.A prospective observational longitudinal study was performed in 127 consecutive patients with moderate or severe AS (68.8 ± 9.2 years of age, 49.6% male) and 33 age- and sex-matched controls who underwent 3-T CMR. The degree of diffuse myocardial fibrosis was assessed by noncontrast mapping of T1 relaxation time using modified Look-Locker inversion-recovery sequence, and the presence and extent of LGE were also evaluated. The AS patients were divided into 3 groups by the native T1 value. Primary endpoint was a composite of all-cause death and hospitalization for heart failure.Native T1 value was higher in AS patients, compared with control subjects (1,232 ± 53 ms vs. 1,185 ± 37 ms; p = 0.008). During follow-up (median 27.9 months), there were 24 clinical events including 9 deaths (6 pre-operative and 3 post-operative), the majority of which occurred in the patients in the highest T1 tertile group (2.4% vs. 11.6% vs. 42.9% for lowest, mid-, and highest tertile groups; p 0.001 by log-rank test). The total number of events for both pre- and post-operative events also occurred more frequently in patients in the highest T1 tertile group. EuroSCORE II, the presence and/or extent of LGE, and the native T1 value were predictors of poor prognosis (adjusted hazard ratio for every 20-ms increase of native T1: 1.28; p = 0.003). In particular, the highest native T1 value provided further risk stratification regardless of the presence of LGE.High native T1 value on noncontrast T1 mapping CMR is a novel, independent predictor of adverse outcome in patients with significant AS.

Objectives This study sought to investigate the prognostic significance of left ventricular (LV) mass and geometry in ischemic stroke survivors, as well as the LV geometry–specific differences in the blood pressure–mortality relationship. Background LV mass and geometry are well-known prognostic factors in various populations; however, there are no data on their role in ischemic stroke patients. Methods We prospectively recruited 2,328 consecutive patients admitted with acute ischemic stroke to our institute between 2002 and 2010. Of these, 2,069 patients were analyzed in whom echocardiographic data were available to assess LV mass and geometry. Results All-cause mortality was significantly greater in patients with concentric hypertrophy (adjusted hazard ratio [HR]: 1.417; 95% confidence interval [CI]: 1.045 to 1.920) and concentric remodeling (HR: 1.540; 95% CI: 1.115 to 2.127) but nonsignificantly in those with eccentric hypertrophy (HR: 1.388; 95% CI: 0.996 to 1.935) compared with normal geometry in multivariate analyses. Relative wall thickness was a significant predictor of all-cause mortality (HR: 1.149 per 0.1-U increase in relative wall thickness; 95% CI: 1.021 to 1.307), whereas LV mass index was not (HR: 1.003 per 1 g/m2 increase in LV mass index; 95% CI: 0.999 to 1.007). Similar results were observed with cardiovascular mortality. In multivariable fractional polynomials, patients with altered LV geometry showed reverse J-curve relationships between acute-phase systolic blood pressure and all-cause or cardiovascular mortality, with the highest risks in the lower extremes, whereas those with normal geometry did not. Conclusions Echocardiographic assessment of LV geometry provided independent and additive prognostic information in ischemic stroke patients. A reverse J-shaped relation of mortality with blood pressure was found in patients with abnormal LV geometry.

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

Objectives Congenital absence of the pericardium (CAP) is often confused with other conditions presenting with right ventricular dilatation and usually warrants CT or cardiac MR (CMR) to confirm. It would be desirable to have more specific echocardiographic criteria to provide a conclusive diagnosis. Methods 11 patients who were diagnosed with CAP (four patients with total CAP) based on CT/CMR were consecutively enrolled. Thirteen patients with atrial septal defect (ASD) and 16 normal subjects served as controls. To investigate spatial changes of heart in the thoracic cavity in CAP, following echocardiographic measurements were made in the left and right decubitus positions: the angle between the ultrasound beam and the left ventricular posterior wall (Angle-PW) in end-diastole at the parasternal long axis, and the distance between the chest wall and the most distal part of the left ventricular posterior wall (Distance-PW) at the parasternal mid-ventricular short axis. Results Angle-PW in patients with CAP were significantly greater than in those with ASD (100.1±12.5° vs 74.5±8.6°, p Conclusions Patients with CAP have dynamic alteration in cardiac position depending on posture, which is not observed in ASD or in normal controls. Hence, total or left-sided CAP can be reliably diagnosed with positional changes during routine echocardiography.

BACKGROUND It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. METHODS This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. RESULTS Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were -20.1 ± 2.3, -19.9 ± 2.7, -21.2 ± 2.6, and -20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were -1.18 ± 0.18, -1.20 ± 0.21, -1.25 ± 0.21, and -1.21 ± 0.21-s, respectively. Females had lower LVGLS (-21.2 ± 2.2% vs. -19.5 ± 1.9%, p < 0.001) and LVGLSR (-1.25 ± 0.18-s vs. -1.17 ± 0.15-s, p < 0.001) values than males. CONCLUSION We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.

Background: The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied. Methods: This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points. Results: During the mean follow-up of 6.3 years, shorter total reproductive years (P -for-trend P -for-trend Conclusions: In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.

Background and Purpose— Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non–vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods— Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results— During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32–0.68), ICH (HR, 0.31; 95% CI, 0.14–0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40–0.96), death (HR, 0.45; 95% CI, 0.31–0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38–0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions— NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.

Background Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. Methods This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). Results CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: − 24.2 ± 2.7% in cirrhosis vs − 18.6 ± 2.2% in healthy controls, P P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P P P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). Conclusions Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p p p

Aims To develop a mortality risk prediction model in patients with acute heart failure (AHF), using left ventricular (LV) function parameters with clinical factors. Methods and results In total, 4312 patients admitted for AHF were retrospectively identified from three tertiary centres, and echocardiographic parameters including LV ejection fraction (LV-EF) and LV global longitudinal strain (LV-GLS) were measured in a core laboratory. The full set of risk factors was available in 3248 patients. Using Cox proportional hazards model, we developed a mortality risk prediction model in 1859 patients from two centres (derivation cohort) and validated the model in 1389 patients from one centre (validation cohort). During 32 (interquartile range 13–54) months of follow-up, 1285 patients (39.6%) died. Significant predictors for mortality were age, diabetes, diastolic blood pressure, body mass index, natriuretic peptide, glomerular filtration rate, failure to prescribe beta-blockers, failure to prescribe renin–angiotensin system blockers, and LV-GLS; however, LV-EF was not a significant predictor. Final model including these predictors to estimate individual probabilities of mortality had C-statistics of 0.75 [95% confidence interval (CI) 0.73–0.78; P Conclusion We developed a mortality risk prediction model for patients with AHF incorporating LV-GLS as the LV function parameter, and other clinical factors. Our model provides an accurate prediction of mortality and may provide reliable risk stratification in AHF patients.

Background and aims Given the potential benefit of medical therapy in patients with non-obstructive coronary artery disease (CAD), there is a need for risk stratification and treatment strategy for these patients. We aimed to develop a risk prediction model for non-obstructive CAD patients for risk stratification and guidance of statin and aspirin therapy. Methods From a cohort of consecutive patients who underwent coronary computed tomography angiography (CCTA) (n = 25,087), we identified patients with non-obstructive CAD of 1–49% diameter-stenosis (n = 6243) and developed a risk prediction model for 5-year occurrence of a composite of all-cause mortality, myocardial infarction, and late coronary revascularization using a derivation cohort (n = 4391). Results Age, sex, hypertension, diabetes, anemia, C-reactive protein, and the extent of non-obstructive CAD were incorporated in the prediction model (risk score 0-13, C-index = 0.716). Patients were categorized into 4 groups; risk score of 0–3 (low-risk), 4-6 (intermediate-risk), 7-9 (high-risk), and ≥10 (very high-risk). Patients with very high-risk demonstrated unfavorable outcome comparable to patients with obstructive CAD. The low-risk group exhibited favorable outcome similar to those with no CAD. While statin therapy was associated with better outcomes in high- or very high-risk group (hazard ratio, 0.62; 95% confidence interval, 0.39–0.96; p = 0.033), aspirin use was associated with an increased risk in low-risk group (hazard ratio, 2.57; 95% confidence interval, 1.34–4.90; p = 0.004). Conclusions A dedicated risk scoring system for non-obstructive CAD using clinical factors and CCTA findings accurately predicted prognosis. According to our risk prediction model, statin therapy can be beneficial for high-risk patients, whereas aspirin can be harmful for low-risk patients.

Similar to left ventricular and aortic pressure waveforms, augmentation pressure (AugPr) in the right ventricular (RV) pressure waveform is also frequent in patients with pulmonary hypertension (PH). This study sought to evaluate whether the degree of AugPr in RV pressure waveform has prognostic value. Forty-one patients (13 men; mean age = 50.7 ± 16.1 years) with group 1 PH (mean pulmonary artery pressure [mPAP] ≥ 25 mmHg) who underwent cardiac catheterization as part of their work-up were retrospectively enrolled. Patients were divided into three groups. Group A: AugPr/RV systolic pressure < 25%; group B: AugPr/RV systolic pressure ≥ 25%; and group C: no discernible AugPr but showing peaked RV pressure waveform. Ten patients were included in group A (male-to-female ratio 3:7; mean age = 45.9 ± 12.1 years), 12 in group B (4:8, 53.8 ± 14.6 years), and 19 in group C (6:13, 51.8 ± 18.7 years). No differences in mPAP were seen between the three groups. Pulse pressure was significantly higher in group C compared to group A. Eight patients died during the mean follow-up period of 35.9 ± 30.7 months; the incidence of death was significantly higher in group C than in the other groups (one patient in group A and seven patients in group C). AugPr in RV pressure waveform has prognostic value in patients with PH. Therefore, additional attention should be given to the RV pressure waveform in patients with PH undergoing invasive pressure measurements as a part of their work-up.

Aims Native T1 times from T1 mapping cardiac magnetic resonance (CMR) are associated with myocardial fibrosis in aortic stenosis (AS). We investigated whether changing patterns in native T1 predict clinical outcomes after aortic valve replacement (AVR) in severe AS patients. Methods and results Forty-three patients with severe AS (65.9 ± 8.1 years; 24 men) who underwent T1 mapping CMR at baseline and 1 year after AVR were prospectively enrolled. Upper limit of native T1 from healthy volunteers was used to define normal myocardium and diffuse fibrosis (native T1 Conclusion AVR-induced changes in native T1 values are associated with LV systolic functional changes as well as prognosis in severe AS. Post-AVR T1 mapping CMR can be used as an imaging biomarker.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is believed to represent dense replacement fibrosis. It is seen in ≈60% of adult patients with hypertrophic cardiomyopathy (HCM). However, the prevalence of LGE in children and adolescents with HCM is not well established. In addition, longitudinal studies describing the development and evolution of LGE in pediatric HCM are lacking. This study assesses the prevalence, progression, and clinical correlations of LGE in children and adolescents with, or genetically predisposed to, HCM.CMR scans from 195 patients ≤21 years of age were analyzed in an observational, retrospective study, including 155 patients with overt HCM and 40 sarcomere mutation carriers without left ventricular (LV) hypertrophy. The extent of LGE was quantified by measuring regions with signal intensity6 SD above nulled remote myocardium.Patients were 14.3±4.5 years of age at baseline and 68% were male. LGE was present in 70 (46%) patients with overt HCM (median extent, 3.3%; interquartile range, 0.8-7.1%), but absent in mutation carriers without LV hypertrophy. Thirty-one patients had1 CMR (median interval between studies, 2.4 years; interquartile range, 1.5-3.2 years). LGE was detected in 13 patients (42%) at baseline and in 16 patients (52%) at follow-up CMR. The median extent of LGE increased by 2.4 g/y (range, 0-13.2 g/y) from 2.9% (interquartile range, 0.8-3.2%) of LV mass to 4.3% (interquartile range, 2.9-6.8%) ( P=0.02). In addition to LGE, LV mass and left atrial volume, indexed to body surface area, and z score for LV mass, as well, increased significantly from first to most recent CMR.LGE was present in 46% of children and adolescents with overt HCM, in contrast to ≈60% typically reported in adult HCM. In the subset of patients with serial imaging, statistically significant increases in LGE, LV mass, and left atrial size were detected over 2.5 years, indicating disease progression over time. Further prospective studies are required to confirm these findings and to better understand the clinical implications of LGE in pediatric HCM.

Purpose Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. Methods In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. Findings : In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. Implications Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.