Search

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. [Display omitted] [ABSTRACT FROM AUTHOR]

• More than 30% of adults with congenital heart disease (CHD) experience depression • Future uncertainty, frustration, and depression can cause irrational thinking • Rational Emotive Behavior Therapy (REBT) can help patients identify, challenge, and replace irrational thinking • REBT may be an effective strategy to reduce depressive symptoms in adults with CHD Over 30% of adults with congenital heart disease (CHD) experience depression. To evaluate the effectiveness of Rational Emotive Behavior Therapy (REBT) in reducing depressive symptoms in adults with CHD. Forty-two adults with CHD were recruited from an outpatient clinic and randomized to a study group (n = 21), which comprised 8-weekly group-based counseling sessions, or a control group (n = 21), which received usual care. REBT effectiveness was examined using the Hamilton Depression Rating Scale, Beck Depression Inventory, Shorten General Attitude and Belief Scale, and salivary cortisol levels before therapy, after the last session, and at follow-up 4 weeks later. Average participant ages were 30.1 ± 7.58 and 33.3 ± 7.1 years in study and control groups, respectively; 52.4% of participants in each group were female. After REBT, depression (p < 0.001), irrational beliefs (p < 0.001), and salivary cortisol levels (p = 0.006) were significantly lower in the study group than in the control group. Effects of REBT in the study group remained consistent at the 4-week follow-up. REBT may be effective in reducing depression in adults with CHD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study assessed diffuse myocardial fibrosis (MF) by cardiac magnetic resonance (CMR) imaging and speckle-tracking echocardiography (STE) in patients with severe aortic stenosis (AS) and validated findings by using histologic confirmation of MF. Background MF is a concomitant pathologic finding related to hypertrophic response in severe AS. It would be beneficial to have reliable imaging methods to assess MF. Methods CMR and STE were performed in 71 consecutive patients with severe AS before aortic valve replacement. The extracellular volume (ECV) and native T1 values obtained by CMR and global longitudinal strain (GLS) values by STE were measured. The degree of MF was quantified by using Masson trichrome stain in myocardial biopsy specimens obtained intraoperatively. The study population was divided into 3 groups according to the degree of MF on histology (mild, moderate, and severe MF). Results The severe MF group had a higher incidence of heart failure (HF) and diastolic dysfunction than the mild and moderate MF groups. The ECV (r = 0.465; p < 0.0001), GLS (r = 0.421; p = 0.0003), and native T1 (r = 0.429; p = 0.0002) values were significantly correlated with the degree of MF. GLS was moderately correlated with ECV (r = 0.455; p = 0.0001) and less with the native T1 (r = 0.372; p = 0.0014) value. The model using ECV (R2 = 0.44; Akaike Information Criterion [AIC] = 55.8) was found to predict the degree of MF most accurately than that with GLS (R2 = 0.35; AIC = 66.84) and the native T1 (R2 = 0.36; AIC = 66.18) value. The secondary endpoint of interest was clinical outcome of a composite of total mortality, admission for HF, or development of HF symptoms. During follow-up (median: 4.6 years), and there were 16 clinical events. Although statistically insignificant, ECV is more closely related to prediction of the clinical outcome than native T1 or GLS. Conclusions ECV as assessed by CMR could be an ideal surrogate marker for diffuse MF in patients with severe AS among all 3 models considered. Graphical abstract [ABSTRACT FROM AUTHOR]

Backgrounds The effect of metformin on survival in patients with pancreatic cancer is controversial. Aims To investigate the beneficial effect of metformin in pancreatic cancer patients. Methods We retrospectively analyzed patients with pancreatic cancer and pre-existing diabetes mellitus type 2 who were treated at Severance Hospital (Seoul, South Korea) between May 2005 and December 2013. Results Among 237 enrolled patients, 117 patients (49.4%) were exposed to metformin. The median overall survival was 13.7 months for the metformin group versus 8.9 months for the non-metformin group ( P = 0.001) In univariate analysis, metformin exposure, low serum carbohydrate antigen 19-9 levels (<1000 U/mL), small tumor size (≤20 mm), no tail involvement, good performance status (ECOG 0 vs. 1 or 2), and resectable cancer stage were associated with favorable survival outcomes (all P < 0.05). In multivariate analysis, in addition to low serum carbohydrate antigen 19-9 levels (<1000 U/mL) and resectable cancer stage, metformin exposure was significantly associated with longer survival with a hazard ratio of 0.61 ( P = 0.001). Additionally, the cumulative duration of metformin use was significantly correlated with a favorable survival outcome. Conclusion Our findings supported that metformin exposure was associated with survival benefits in patients with pancreatic cancer and pre-existing type 2 diabetes mellitus, especially among those with an advanced cancer stage. [ABSTRACT FROM AUTHOR]

In a recent randomized controlled trial, a double bare metal stent (DBS) showed better stent patency than single-layer metal stents. However, clear evidence comparing the efficacy of uncovered (UCDBS) and partially covered (PCDBS) DBSs for distal malignant biliary obstruction (MBO) is lacking. Therefore, we compared the clinical outcomes including stent patency of UCDBSs versus PCDBSs. A multicenter, randomized study was performed in patients with distal MBO. The primary endpoint was stent patency. Secondary endpoints were the proportion of patients with patent stents at 6 months, risk factors for stent dysfunction, overall survival, technical and clinical success rates of stent placement, and other adverse events (AEs). Among 258 included patients, 130 were randomly assigned to the PCDBS group and 128 to the UCDBS group. The mean duration of stent patency of the PCDBS (421.2 days; 95% confidence interval [CI], 346.7-495.7) was longer than that of the UCDBS (377.4 days; 95% CI, 299.7-455.0), although total stent dysfunction and stent dysfunction within 6 months were not different between groups. Multivariate analysis indicated that chemotherapy after stent placement was a significant factor for overall survival (hazard ratio,.570; 95% CI,.408-.796) and had a marginal impact on stent patency (hazard ratio, 1.569; 95% CI,.923-2.667). There were no remarkable differences in AEs, including pancreatitis, cholecystitis, and stent migration, between the 2 groups. The use of PCDBSs compared with UCDBSs in patients with distal MBO has unclear benefits regarding stent patency and overall survival, although PCDBSs have a lower rate of tumor ingrowth. (Clinical trial registration number: NCT 02937246.) [Display omitted] [ABSTRACT FROM AUTHOR]

Unlabelled: Conflict persists regarding whether the presence of early collateral blood flow to the infarct-related artery has an effective role in reducing infarct size and improving myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI). We sought to investigate the impact of the collateral circulation on myocardial salvage and infarct size in STEMI patients.Methods: In 306 patients who were diagnosed with STEMI and underwent cardiac magnetic resonance within 1 week after revascularization, initial collateral flow to the infarct-related artery was assessed by coronary angiography. Using cardiac magnetic resonance imaging, myocardial infarct size and salvage were measured.Results: Among 247 patients with preprocedural Thrombolysis in Myocardial Infarction flow 0/1, 54 (22%) patients had good collaterals (Rentrop grade ≥ 2, Collateral Connection Score ≥ 2). Infarct size and area at risk were significantly smaller in patients with good collaterals than those with poor collaterals (infarct size: 17.1 ± 10.1 %LV vs 21.8 ± 10.5 %LV, P = .003, area at risk: 33.8 ± 16.8 %LV vs 38.8 ± 15.5 %LV, P = .039). There was a significant difference of myocardial salvage index between 2 groups (50.9% ± 15.0% vs 43.8% ± 18.5%, P = .005). Poor collateralization was an independent predictor for large infarct size (odd ratio 2.48 [1.28-4.80], P = .007).Conclusions: In patients with STEMI, the presence of well-developed collaterals to occluded coronary artery from the noninfarct vessel and its extent were independently associated with reduced infarct burden and improved myocardial salvage. Our results help explain why MI patients with well-developed collateralization have reduced mortality and morbidity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate intracardiac hemodynamic idiosyncrasies responsible for various presentations of severe aortic stenosis (AS). Background: Syncope, dyspnea, and chest pain are well-established indications for aortic valve replacement in patients with severe AS. Patients'' survival is limited once they develop symptoms from AS, and survival depends on what type of symptoms a patient develops. We hypothesized that there would be a relationship between the type of AS symptoms and intracardiac hemodynamics as well as AS severity. Methods: We analyzed 498 patients (men: 58.4%, 66 ± 12 years of age) with severe AS and normal left ventricular ejection fraction from 2003 to 2009 who had comprehensive echocardiography examination for AS. The study population was divided into 4 groups based on presenting symptom(s) (341 in group I, asymptomatic; 15 in group II, syncope; 110 in group III, dyspnea; 32 in group IV, chest pain). Echocardiographic measurements for cardiac structure, function, and intracardiac hemodynamic parameters were compared among these 4 groups. Results: Mean aortic valve pressure gradient and aortic valve area were 57.1 ± 15.2 mm Hg and 0.74 ± 0.19 cm2, respectively. AS severity based on mean gradient and aortic valve area was similar among 4 groups. Compared with the asymptomatic group, symptomatic patients were older and had lower cardiac output, and higher E/e'' ratio while having a similar aortic valve area and gradient. Group II (syncope) displayed smaller LV dimension, stroke volume, cardiac output, left atrial volume index, and E/e'' ratio. Conversely, group III (dyspnea) was found to have the worst diastolic function with largest left atrial volume index and highest E/e'' ratio. Conclusions: Among patients with severe AS, their symptoms are often linked to specific hemodynamic patterns associated with AS: smaller left ventricular cavity and reduced output for syncope versus more advanced diastolic dysfunction for dyspnea. Hence, comprehensive intracardiac hemodynamics including diastolic function and stroke volume need to be evaluated in addition to aortic valve area and pressure gradient for assessment of AS. [Copyright &y& Elsevier]

Objectives: The aims of this study were to: 1) compare early diastolic mitral annular velocity (E′) of septal annulus (SE′) with E′ of lateral mitral annulus (LE′) and right lateral tricuspid annulus (RE′) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM); and 2) assess the relationship between pericardial thickness measured by computed tomography and lateral E′ velocity. Background: The SE′ velocity has been shown to be able to distinguish CP from RCM. However, tissue Doppler parameters of LE′ and RE′ velocities in patients with CP have not been comprehensively analyzed in comparison with SE′. Moreover, the impact of pericardial thickness on the lateral annulus velocity has not been assessed. Methods: Thirty-seven patients with CP, 35 patients with RCM, and 70 normal controls were evaluated with echocardiography including SE′, LE′, and RE′. In CP, the maximal pericardial thicknesses on both left and right ventricle were measured by computed tomography. Results: Mean LE′/SE′ (ratio between mitral LE′ and SE′) was 0.94 ± 0.17 and RE′/SE′ (ratio between tricuspid RE′ and mitral SE′) was 0.81 ± 0.26 in patients with CP, which were lower than those in normal controls (LE′/SE′ 1.36 ± 0.24; RE′/SE′ 1.30 ± 0.32; both p < 0.001) and patients with RCM (LE′/SE′ 1.35 ± 0.31; RE′/SE′ 1.96 ± 0.71; both p < 0.001). There was a significant inverse correlation between right pericardial thickness and RE′ (ρ = −0.489; p = 0.002) and similar trend between left pericardial thickness and LE′ (ρ = −0.284; p = 0.089). Conclusions: The ratio between lateral and septal E′ was significantly reduced in patients with CP compared with that in normal control patients and patients with RCM so that the reduced ratios of LE′/SE′ and RE′/SE′ appear to be a useful diagnostic parameter for CP. Moreover, reduced lateral E′ was correlated with the pericardial thickness on their respective sides. [Copyright &y& Elsevier]

Objectives: The aim of this study was to investigate whether preoperative estimated left ventricular filling pressure predicts the postoperative outcome in patients with severe aortic stenosis. Methods: Two hundred ten patients who underwent isolated aortic valve replacement because of severe aortic stenosis were analyzed. Left ventricular filling pressure was noninvasively assessed based on the ratio between early diastolic mitral inflow and mitral annular velocity (E/E′), which was calculated based on results of mitral inflow and mitral annular tissue Doppler scanning. Early postoperative hospital events were reviewed. Postoperative mortality and morbidity were searched and compared according to left ventricular filling pressure. Results: Preoperative functional class was associated with increased E/E′ values. Postoperative hospital events were higher in patients with increased preoperative E/E′ values. Midterm mortality of the overall population was very low after aortic valve replacement (2%). Cardiovascular event-free survival, including hospital visits caused by heart failure symptoms, embolic cerebral infarction, and sudden cardiac death, was significantly lower in the patients with increased left ventricular filling pressure and E/E′ values of greater than 12 (P = .03). Multivariable analysis showed a high hazard ratio of increased E/E′ values of greater than 12 (hazard ratio, 41; P < .001). Conclusions: The incidence of postoperative mortality after isolated aortic valve replacement caused by severe aortic stenosis is relatively low in the current era. E/E′ representing diastolic filling pressure is the most important preoperative predictor of risk of early postoperative hospital course and postoperative morbidity. [Copyright &y& Elsevier]

Abstract: Purpose: Although takotsubo cardiomyopathy (TTC) has been reported to have an excellent clinical recovery, there are few data regarding clinical, laboratory, and echocardiographic findings in TTC presenting as cardiogenic shock. We aimed to assess the differences in these parameters between TTC presenting with and without cardiogenic shock. Methods: Fifty patients were enrolled from the TTC registry database and divided according to the presence of cardiogenic shock. Sixteen patients presented with cardiogenic shock as initial presentation (S group), and 34 did not (NS group). Results: The S group had a higher prevalence of dyspnea (81% vs 38%, P = .005), pulmonary edema (69% vs 29%, P = .009), and significant reversible mitral regurgitation (44% vs 15%, P = .025) than the NS group. In addition, the S group had significantly higher troponin-I (median, 8.2 vs 1.4 pg/mL; P = .043) and N-terminal prohormone brain natriuretic peptide levels (median, 8831 vs 2348 pg/mL; P = .046). During follow-up (median, 3.1 years), cardiac deaths associated with TTC itself and recurrences of TTC were not noted in both groups. Conclusions: The S group has a higher prevalence of heart failure symptoms, significant reversible mitral regurgitation, and troponin-I and N-terminal prohormone brain natriuretic peptide levels. However, with meticulous therapeutic strategies, prognosis of this syndrome may be excellent irrespective of hemodynamic instability. [Copyright &y& Elsevier]

Objective: Although patients with transient left ventricular ballooning syndrome (TLVBS), also known as Takotsubo cardiomyopathy, improve rapidly and recover left ventricular systolic function, the long-term prognosis is not well-known. This study investigated the clinical features of TLVBS, and its in-hospital and long-term (in-hospital plus postdischarge) mortality. Methods and Results: We evaluated 87 patients diagnosed with TLVBS. The median follow-up was 42 months (interquartile range, 19 to 72 months). During follow-up, no recurrences were reported, but 20 (23%) patients died. Two nonsurvivors (2%) were suspected of dying from sudden cardiac death. The in-hospital total mortality rate was 9%, but the in-hospital cardiac mortality rate was 0%. Most deaths were associated with underlying noncardiac diseases. Baseline characteristics were mostly similar between survivors and nonsurvivors. However, nonsurvivors were older, and more likely to be smokers compared with survivors. Underlying noncardiac diseases were the only independent predictors of long-term mortality (hazard ratio, 3.954; 95% confidence interval, 1.369 to 11.422; P =.011). There were no significant differences in long-term mortality, according to the preceding stress events or ballooning patterns. Conclusions: Although a substantial number of patients with TLVBS die, the long-term cardiac mortality is low. The severity of heart failure owing to TLVBS may influence in-hospital mortality, whereas underlying noncardiac diseases have a more significant correlation with the long-term prognosis than does TLVBS itself. [Copyright &y& Elsevier]

Objective: This study was designed to identify variables associated with depression in adolescents who underwent operation for congenital heart disease (CHD). Methods: Data were collected from 231 adolescents, aged 13 to 18 years with CHD, during outpatient clinic follow-up after open heart surgery in 3 major cardiac centers in Korea. Adolescents completed measures of resilience, depression, and parental attitude. Their New York Heart Association functional class, CHD functional index, and noninvasive saturation of arterial oxygen were also measured. Results: There were significantly positive relations between depression and the 3 variables: older age, worse New York Heart Association functional class, and higher CHD functional index. Negative relations were found between depression and higher saturation of arterial oxygen, higher academic achievements, affectionate parental attitude, and higher resilience. The multiple regression analysis also showed that 62% of the variance in depression in adolescents with CHD could be explained by resilience and parental attitude. Conclusion: This study demonstrated that adolescents with higher resilience and an affectionate parent were less depressed. [Copyright &y& Elsevier]

Background: EUS is an accurate imaging modality for delineating gallbladder (GB) structures; however, its clinical use in differentiating neoplastic GB polyps from nonneoplastic polyps is limited. Thus, we sought to characterize neoplastic GB polyps by analyzing unique EUS features. Our analysis revealed variably shaped, relatively hypoechoic portions in the core of polyps compared with general background echogenicity. Objective: Our purpose was to make a differential diagnosis between neoplastic and nonneoplastic GB polyps of less than 20 mm by use of EUS variables, including hypoechoic foci. Design: Retrospective single-center study. Setting: University teaching hospital. Patients: Patients (n = 88) underwent preoperative EUS and cholecystectomy for GB polyps smaller than 20 mm. Results: Hypoechoic foci were found in 30 of 33 patients (91%) with neoplastic polyps and 6 of 55 (11%) with nonneoplastic polyps. In a multivariate analysis, hypoechoic foci were the only significant predictive factor for neoplastic polyps (odds ratio [OR] 55.4, 95% CI, 8.26-371, P < .001); the sensitivity and specificity were 90% and 89%, respectively. In addition, polyps >15 mm had an increased risk of malignancy (OR 21.7, 95% CI, 2.35-201, P = .007), as did those with hypoechoic foci (OR 10.9; 95% CI, 1.01-117, P = .049). Limitations: Retrospective review of selected patients from a tertiary medical center. Conclusions: The presence of hypoechoic foci on EUS is a strong predictive factor for neoplastic polyps. EUS may be useful in developing a treatment strategy for GB polyps. [Copyright &y& Elsevier]

Background & Aims: Although the cell of origin for pancreatic cancer remains unknown, prior studies have suggested that pancreatic neoplasia may be initiated in progenitor-like cells. To examine the effects of oncogene activation within the pancreatic progenitor pool, we devised a system for real-time visualization of both normal and oncogenic KRAS-expressing pancreatic progenitor cells in living zebrafish embryos. Methods: By using BAC transgenes under the regulation of ptf1a regulatory elements, we expressed either extended green fluorescent protein (eGFP) alone or eGFP fused to oncogenic KRAS in developing zebrafish pancreas. Results: After their initial specification, normal eGFP-labeled pancreatic progenitor cells were observed to actively migrate away from the forming endodermal gut tube, and subsequently underwent characteristic exocrine differentiation. In contrast, pancreatic progenitor cells expressing oncogenic KRAS underwent normal specification and migration, but failed to differentiate. This block in differentiation resulted in the abnormal persistence of an undifferentiated progenitor pool, and was associated with the subsequent formation of invasive pancreatic cancer. These tumors showed several features in common with the human disease, including evidence of abnormal Hedgehog pathway activation. Conclusions: These results provide a unique view of the tumor-initiating effects of oncogenic KRAS in a living vertebrate organism, and suggest that zebrafish models of pancreatic cancer may prove useful in advancing our understanding of the human disease. [Copyright &y& Elsevier]