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This study aimed to investigate the progression of mild-to-moderate aortic stenosis (AS) in patients with end-stage renal disease (ESRD) and determine its metabolic and hemodynamic contributors and clinical outcomes. A total of 74 patients with ESRD (50 men, age 72 ± 11 years) with mild-to-moderate AS were compared with 79 age- and gender-matched controls with normal kidney function. Clinical, laboratory, and echocardiographic features and clinical outcomes including aortic valve (AV) intervention, hospitalization due to heart failure, and cardiovascular death were analyzed. Patients with ESRD were divided into 2 subgroups according to their rate of AV area changes (group 1 [n = 28], rapid progression; and group 2 [n = 46], slow progression). Progression in the degree of AS was noted in 38% of patients with ESRD and 18% of controls (p <0.01) during comparable echocardiographic follow-up durations (29 ± 15 vs 27 ± 24 months, respectively, p = 0.57). In ESRD, patients in group 1 were older (p <0.01) with higher baseline log parathyroid hormone (p <0.01) and larger stroke volume (p = 0.03) than those in group 2. During clinical follow-up (48 ± 23 months), patients in group 1 showed poorer clinical outcomes than those in group 2 and controls (log-rank p <0.01). Age, left atrial volume index ≥42 ml/m2, and annual increases of peak pressure gradient across the AV (mm Hg/year) demonstrated additive predictive values for prognosis. AS in ESRD progresses in an accelerated manner along with higher metabolic and hemodynamic loads on AV compared with those with normal kidney function. Accelerated progression of mild-to-moderate AS in ESRD results in poor prognosis.

Conflicting data exist regarding the association of body mass index (BMI) changes with all-cause and cardiovascular (CV) mortality. The current study investigated the association between changes in BMI and all-cause, CV, and non-CV mortality in a large cohort of middle-aged adults. A total of 379,535 adults over 40 years of age without pre-existing CV disease or cancer at baseline were enrolled to undergo a series of at least three health examinations of biennial intervals. Changes in BMI between baseline, midpoint follow-up, and final health examination during mean 9.3 years were defined according to the pattern of BMI change as follows: stable, sustained gain, sustained loss, and fluctuation. The relationship between BMI change category and mortality was assessed by multivariate Cox regression reporting hazard ratio (HR) with 95% confidence interval (95% CI). During a mean follow-up of 10.7 years for mortality, 12,378 deaths occurred from all causes, of which 2,114 were CV and 10,264 were non-CV deaths. Sustained BMI gain was associated with the lower risk of all-cause (HR 0.89, 95% CI: 0.83-0.95), CV (HR 0.84, 95% CI 0.72-0.98), and non-CV mortality (HR 0.90, 95% CI 0.84-0.96) compared with stable BMI. Conversely, sustained BMI loss (HR 1.25, 95% CI 1.19-1.32) and fluctuation (HR 1.13, 95% CI 1.08-1.19) displayed a higher risk of all-cause mortality compared with stable BMI, which was mainly attributable to the increase in non-CV mortality. Sustained BMI gains were associated with reduced risk of all-cause, CV, and non-CV mortality in middle-aged healthy adults.

We aimed to identify the clinical and echocardiographic determinants of symptoms and their prognostic implications in patients with moderately dysfunctional bicuspid aortic valves (BAVs). Among 1,019 subjects in the BAV registry treated in a single tertiary care center, the records of 127 patients (85 men, age 58±13 years) with moderately dysfunctional BAVs were comprehensively reviewed. The patients were divided into two groups based on symptom status: asymptomatic (n = 80) vs. symptomatic (n = 47). The primary end-point was defined as a composite of aortic valve surgery, hospitalization for heart failure, and any cause of death. The symptomatic group had a higher proportion of females, hypertension, aortic stenosis, and aortopathy than did the asymptomatic group. The symptomatic group showed lower e' (5.5±1.7 vs. 6.5±2.2 cm/s, p = 0.003), higher E/e' (13.3 ± 4.9 vs. 10.9±3.7, p = 0.002), and larger left atrial volume index (29.9±11.4 vs. 24.6±9.1 ml/m2, p = 0.006) than did the asymptomatic group. In multivariate logistic regression analysis, female gender (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.10-7.36, p = 0.031), hypertension (OR 3.07, 95% CI 1.20-7.82, p = 0.019), moderate aortic stenosis (OR 5.33 5.78, 95% CI 1.99-16.83, p = 0.001), E/e' >15 (OR 3.82, 95% CI 1.03-11.19, p = 0.015), and aortopathy (OR 2.76, 95% CI 1.07-7.10, p = 0.035) were independently correlated with symptom status. The symptomatic group showed a significantly lower rate of event-free survival during the 8-year follow-up period (54±9% vs. 68±10%, p = 0.001). In patients with moderately dysfunctional BAVs, the presence of moderate aortic stenosis, aortopathy, and diastolic dysfunction determines symptom status, along with female gender and hypertension. Symptom status was associated with clinical outcomes.

Unprovoked venous thromboembolism (VTE) is related to a higher incidence of occult cancer. D-dimer is clinically used for screening VTE, and has often been shown to be present in patients with malignancy. We explored the predictive value of D-dimer for detecting occult cancer in patients with unprovoked VTE. We retrospectively examined data from 824 patients diagnosed with deep vein thrombosis or pulmonary thromboembolism. Of these, 169 (20.5%) patients diagnosed with unprovoked VTE were selected to participate in this study. D-dimer was categorized into three groups as: <2,000, 2,000-4,000, and >4,000 ng/ml. Cox regression analysis was employed to estimate the odds of occult cancer and metastatic state of cancer according to D-dimer categories. During a median 5.3 (interquartile range: 3.4-6.7) years of follow-up, 24 (14%) patients with unprovoked VTE were diagnosed with cancer. Of these patients, 16 (67%) were identified as having been diagnosed with metastatic cancer. Log transformed D-dimer levels were significantly higher in those with occult cancer as compared with patients without diagnosis of occult cancer (3.5±0.5 vs. 3.2±0.5, P-value = 0.009, respectively). D-dimer levels >4,000 ng/ml was independently associated with occult cancer (HR: 4.12, 95% CI: 1.54-11.04, P-value = 0.005) when compared with D-dimer levels <2,000 ng/ml, even after adjusting for age, gender, and type of VTE (e.g., deep vein thrombosis or pulmonary thromboembolism). D-dimer levels >4000 ng/ml were also associated with a higher likelihood of metastatic cancer (HR: 9.55, 95% CI: 2.46-37.17, P-value <0.001). Elevated D-dimer concentrations >4000 ng/ml are independently associated with the likelihood of occult cancer among patients with unprovoked VTE.

This study aimed to investigate the incidence, predictors, and clinical outcomes of cardiac tamponade after heart valve surgery. A total of 556 patients who underwent heart valve surgery in a single tertiary center between January 2010 and March 2012 were studied. All patients underwent transthoracic echocardiography (TTE) about 5 days after surgery and TTE was repeated regularly. Patients with suspected acute pericardial hemorrhage were excluded. Cardiac tamponade occurred in twenty-four (4.3%) patients and all underwent surgical or percutaneous pericardial drainage. The median time of pericardial drainage after surgery was 17 (interquartile range, IQR, 13-30) days. Infective endocarditis, mechanical valve replacement of aortic or mitral valve, and any amount of pericardial effusion (PE) on the first postoperative TTE were related to the occurrence of cardiac tamponade (all p<0.05). After multivariate adjustment, occurrence of cardiac tamponade was associated with any amount of PE on the first postoperative TTE (hazard ratio, HR, 14.00, p<0.001) and mechanical valve replacement (HR 2.69, p = 0.025). The mean hospital days in patients with cardiac tamponade was higher than those without (34.9 vs. 13.5, p = 0.031). After pericardial drainage, there was no echocardiographic recurrence of significant PE during a median of 34.8 (IQR 14.9-43.7) months after surgery. Cardiac tamponade after heart valve surgery is not uncommon. Patients with any amount of PE at the first postoperative TTE or mechanical valve replacement should receive higher attention with regard to the occurrence of cardiac tamponade. Although it prolongs hospital stay, cardiac tamponade exhibits a benign clinical course without recurrence after timely intervention.

Bicuspid aortic valve (BAV) disease has a male predominance of approximately 3:1 and shows diverse presentations about aortic valve dysfunction. This study aimed to find independent determinants for significant aortic stenosis (AS) or significant aortic regurgitation (AR) in adults with BAV. We retrospectively investigated the medical records of 1,073 subjects (773 men, mean age 55 ± 14 years) who were first diagnosed with BAV disease by transthoracic echocardiography. We excluded 52 subjects with both significant AS and significant AR. Of the remaining 1,021 subjects, 418 (41%) presented with significant AS, 249 (24%) showed significant AR, and the rest of the subjects were grouped into a normal functioning BAV (n = 354, 35%). BAV morphology was classified into the following 4 types according to position and pattern of raphe and cusps: (1) fusion of the right and left coronary cusps (type 1), (2) fusion of the right and noncoronary cusps (type 2), (3) fusion of the left and noncoronary (type 3), and (4) no raphe (type 0). Patients with significant AS were older, more likely to be women than men, and had a higher prevalence of type 0 BAV. Patients with significant AR were younger and were more likely to be men. In multivariate logistic regression analysis, women, older age, and type 0 or type 3 BAV were associated with significant AS. In contrast, men, hypertension, and chronic kidney disease were correlated with significant AR. Significant valve dysfunction in adults with first diagnosed BAV was closely associated with age, gender, and BAV morphology.

A bicuspid aortic valve (BAV) is often associated with dilation or aneurysm of the ascending aorta (AA) despite of absence of significant valve dysfunction. Bicuspid aortopathy and consequent aortic stiffness may adversely affect left ventricular (LV) diastolic function. This study aimed to investigate the impact of global and regional aortic mechanical function on LV diastolic function in subjects with BAV. Fifty-six subjects with BAV (45 men, mean age 52 ± 13 years) without significant valve dysfunction and 56 age- and gender-matched controls with tricuspid aortic valve were studied. The aortic phenotypes were classified into 3 groups: normal shape, predominant dilatation of the sinus of Valsalva, and predominant dilatation of the AA. Structural and functional parameters of the AA and LV were measured using 2-dimensional echocardiography. Global aortic mechanical function was assessed by radial artery tonometry. The subjects with BAV showed a higher incidence of a predominant AA phenotype (53.6% vs 17.9%, p <0.001), larger indexed aortic diameters, increased augmentation index, lower pulse pressure amplification, lower early diastolic mitral annular (e’) velocity, and higher E/e’ than those with tricuspid aortic valve . The e’ velocity and E/e’ varied with different aortic phenotypes in subjects with BAV. Correlations between e’ velocity and parameters of aortic stiffness were stronger in subjects with BAV than those in controls. Multiple regression analysis revealed that augmentation index normalized for a heart rate of 75 beats/min was an independent determinant of e’ velocity (β = −0.24, p = 0.044) and E/e’ (β = 0.30, p = 0.018) in subjects with BAV even after controlling for confounding factors. LV diastolic function is closely related to aortic phenotype and mechanical alteration in subjects with BAV.

This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

Although intensive statin therapy is recommended for high risk patients, evidence of its benefit in patients with stable coronary artery disease (CAD) and very low low-density lipoprotein-cholesterol (LDL-C) has been very rare. In this study, we investigated whether higher statin intensity reduces cardiovascular risks in this population. In this retrospective study, a total of 5234 patients with stable CAD were screened at three tertiary hospitals in Korea; 449 patients (mean age: 65 years, male: 69%) with LDL-C <80 mg/dL were finally analyzed. The statin intensities were classified according to the 2013 American College of Cardiology/American Heart Association guidelines. Patients who received statins equivalent to or weaker than atorvastatin 10 mg (group 1) were compared with those who took statins equivalent to or stronger than atorvastatin 20 mg (group 2). The impact of statin intensity on major adverse cardiac events (MACE) was evaluated during follow-up. Group 1 and group 2 consisted of 181 patients (40.3%) and 268 patients (59.7%), respectively. The mean LDL-C level decreased to 52 and 57 mg/dL in group 1 and group 2, respectively, during follow-up. In a median follow-up of 4.5 years, patients of group 2 had a lower incidence of MACE (30 [16.6%] vs. 12 [4.5%], p <0.001), which were mostly related to a lower incidence of coronary revascularization. Cox proportional hazard analyses identified the statin intensity of group 2 (adjusted hazard ratio: 0.25, confidence interval: 0.11-0.55, p <0.001) and the baseline high-density lipoprotein-cholesterol level as independent determinants of MACE. This study provides evidence that higher intensity statins are beneficial for cardiovascular outcomes in patients with stable CAD and very low LDL-C. Statins equivalent to or stronger than atorvastatin 20 mg are more effective than lower intensity statins.

Echocardiographic signs of constrictive physiology (CP) after pericardiocentesis are frequently observed in malignancy patients. The purpose of the current study was to explore whether features of CP after pericardiocentesis have prognostic impact in malignancy patients with pericardial effusion (PE). We retrospectively reviewed 467 consecutive patients who underwent pericardiocentesis at our institution from January 2006 to May 2014. Among them, 205 patients with advanced malignancy who underwent comprehensive echocardiography after the procedure comprised the study population. Co-primary end points were all-cause mortality (ACM) and repeated drainage (RD) for PE. Patients were divided into four subgroups according to cytologic result for malignant cells and CP (positive cytology with negative CP, both positive, both negative, and negative cytology with positive CP). CP after pericardiocentesis was present in 106 patients (50%) at median 4 days after the procedure. During median follow-up of 208 days, ACM and RD occurred in 162 patients (79%) and 29 patients (14%), respectively. Cox regression analysis revealed that independent predictors for ACM were male gender and positive cytology (all, p < 0.05). For RD, predictors were positive cytology, the absence of cardiac tamponade, and negative CP after pericardiocentesis (all, p < 0.05). When the patients were divided into four subgroups, patients with negative cytology and positive CP demonstrated the most favorable survival (hazard ratio [HR]: 0.39, p = 0.005) and the lowest RD rates (HR: 0.07, p = 0.012). CP after pericardiocentesis is common, but does not always imply poor survival or the need for RD in patients with advanced malignancies. On the contrary, the presence of CP in patients with negative cytology conferred the most favorable survival and the lowest rate of RD. Comprehensive echocardiographic evaluation for CP after pericardiocentesis would be helpful for predicting prognosis in patients with advanced malignancies.