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Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics.The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data.Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups.The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003).The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

(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.

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.

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

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p

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

Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis, 99 mTc-DPD scintigraphy (DPD scan) is a useful diagnostic modality for wtTTR amyloidosis.We retrospectively analyzed patients older than 30 years who underwent DPD scanning for non-cardiac reasons at our hospital between June 2014 and March 2017 (n = 9,581). Transthoracic echocardiography was used to assess left ventricular hypertrophy (LVH), as well as systolic and diastolic function.A positive DPD scan was observed in only six patients (0.06%). All six of these patients were older than 70 years, and they constitute only 0.4% of patients in this age group (6/1652). Among the patients with a positive DPD scan, four showed concentric LVH and two showed a normal wall thickness. With respect to the severity of diastolic dysfunction and pulmonary artery pressure, patients with a positive DPD scan showed the expected E' and pulmonary artery systolic pressure for their age.Even considering the limited sensitivity of a positive DPD scan detecting wtTTR amyloidosis, the incidence of a positive DPD scan in non-cardiac patients indicated that wtTTR amyloid deposition does not seem to be a major cause for age-related diastolic dysfunction, nor does appear to have a high incidence in patients with heart failure with preserved EF in the elderly.

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 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.

BACKGROUND The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler

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 Aortic stenosis (AS) induces significant pressure overload to the left ventricle (LV) and its burden may increase if there is concomitant LV systolic dysfunction. Severe AS with LV systolic dysfunction is a class I indication for aortic valve replacement (AVR) irrespective of symptoms, however, this recommendation is not well established in those with moderate AS and LV systolic dysfunction. In this study, we sought to investigate the clinical impact of surgical AVR among patients with moderate AS and LV systolic dysfunction. Methods From 2001 to 2017, we retrospectively but consecutively identified patients with moderate AS and LV systolic dysfunction from a single tertiary hospital. Moderate AS was defined as aortic valve area between 1.0 and 1.5cm2 and LV systolic dysfunction as LV ejection fraction less than 50%. The primary outcome was all-cause death and we additionally analyzed cardiac death as a secondary endpoint. The outcomes were compared between those who underwent early surgical AVR at the stage of moderate AS versus those who were followed without AVR at the outpatient clinic. Results Among a total of 257 patients with moderate AS and concomitant LV systolic dysfunction (70.0 ± 11.3 years, 63.4% of male), 34 patients received early AVR. Patients in the AVR group was younger than the observation group (64.2 ± 8.1 vs. 70.9 ± 11.5, respectively), and had a lower prevalence of hypertension and chronic kidney disease. During a mean of 3-year follow up, 112 patients (47.5%) died and the overall death rate was 15.367 per 100 person-year (PY). The AVR group showed a significantly lower rate of all-cause death than the observation group (5.241PY vs. 18.160PY, p-value = 0.002). After multivariable Cox proportional hazard regression adjusting for age, sex, comorbidities and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of all-cause death (hazard ratio [HR] 0.340, 95% confidence interval [CI] 0.117 - 0.985, p-value = 0.047). However, there was no risk reduction of cardiac death (HR 0.578 95% CI 0.150 - 2.231, p-value = 0.426). Conclusions In patients with moderate AS and LV systolic dysfunction, AVR reduces the risk of all-cause death. A prospective design study is warranted to confirm our findings in the near future. Abstract P1274 Figure. Kaplan-Meier curves for deaths

[Background]Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-relatedsymptoms because of subjectivity.However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. [Purpose] The purpose of this study was to clarify actual values for echocardiographic parameters related to severity of MR and determinant factors of MR-related symptoms. [Methods] Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by NYHA (≤ II or ≥ III). [Results]MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2(severe) (p [Conclusions] LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR. Determinant factors for mitral regurgita Model 1 Model 2 OR (95% CI) P-value OR (95% CI) P-value Age, per 1-y increment 1.03 (1.00-1.05) 0.035 1.02 (0.99-1.05) 0.053 Sex (female) 2.23 (1.20-4.16) 0.011 2.28 (1.31-3.98) 0.004 Hear rate, per 1 bpm increment 1.03 (1.00-1.05) 0.025 1.03 (1.01-1.05) 0.007 LVDs index, per 1 mm increment 0.99 (0.90-1.09) 0.90 EF, per 1% increment 0.95 (0.92-0.99) 0.019 0.96 (0.93-0.98) 40 mmHg 2.11 (0.97-4.57) 0.057 Hypertention 1.40 (0.75-2.63) 0.29

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.

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.

OBJECTIVES Patients with very severe aortic stenosis (AS) have extremely poor clinical outcomes even if they are asymptomatic compared to those with severe AS, but the clinical and echocardiographic characteristics of patients with very severe AS remain unclear. METHODS The Asian Valve Registry is a prospective, multicenter, multinational registry for the study and identification of the incidence, natural course, clinical outcomes, and prognostic factors for patients with significant AS at 9 centers in Asian countries. Severe AS was observed in 367 of 1066 patients with AS, and 212 were classified as very severe AS, defined as a peak aortic valve velocity ≥5.0 m/s or a mean aortic valve gradient ≥60 mm Hg. RESULTS The prevalence of NYHA functional class II-IV among patients with very severe AS was significantly higher than that among patients with severe AS (67.9% vs 51.5%, P

We read with great interest the paper by Ito et al. [(1)][1] and their previous publication [(2)][2]. Even with our current sophisticated technology, evaluation of myocardial contractility is quite limited, as we do not have any parameter that is truly independent of loading condition. For this

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.

We appreciate the thoughtful comments by Drs. Zhao and Yang on our recent paper ([1][1]), which was built on our observations 5 years ago ([2][2]). Cardiac troponin and N-terminal natriuretic peptide B have prognostic value in patients with light-chain amyloidosis, as they indicate cardiac

Background Adjustment for pressure recovery (PR) may reconcile discrepancies in pressure gradients measured by Doppler echocardiography and direct catheterization in patients with mild to moderately severe aortic stenosis (AS). The aim of this study was to evaluate whether PR adjustment is useful in a large cohort of predominantly patients with severe AS. Methods Data from 697 patients (mean age 70 ± 11 years) in the Asian Valve Registry with a mean aortic valve area (AVA) of 0.8 ± 0.3 cm2 and a mean gradient of 46 ± 21 mm Hg were analyzed. PR-adjusted AVAs were calculated using validated equations. The primary outcome included aortic valve replacement, all-cause mortality, and hospitalization for heart failure during the median follow-up period of 2.9 years. Results Before PR adjustment, 521 patients showed AVA values of ≤1.0 cm2, and after PR adjustment, 129 (24.8%) were reclassified to moderate AS with a mean AVA of 1.1 ± 0.1 cm2. PR adjustment decreased the frequency of low-gradient severe AS (AVA ≤ 1.0 cm2 and mean gradient 95%) occurred in patients with aortic dimensions Conclusions Clinically relevant PR frequently occurs in patients with moderate to severe AS. PR adjustment has prognostic implications, and accurate classification of severe AS can help prevent discordant AS grading.

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.

Senile or wild-type transthyretin (wtTTR) amyloidosis is an age-related disease caused by the deposition of wtTTR amyloid protein. In contrast to light chain amyloidosis