Development and External Validation of a Deep Learning Algorithm for Prognostication of Cardiovascular Outcomes

BACKGROUND AND OBJECTIVES: We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression. METHODS: Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included. RESULTS: Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886-0.907) in men and 0.921 (0.908-0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860-0.876) in men and 0.889 (0.876-0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824-0.897) in men and 0.867 (0.830-0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women). CONCLUSIONS: A DL algorithm exhibited greater discriminative accuracy than Cox model approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02931500.ope

Effect of anemia correction on left ventricular structure and filling pressure in anemic patients without overt heart disease

Background/Aims: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. Methods: In total, 34 iron-deficiency anemia patients (35 ± 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. Results: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/ E’), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E’ also decreased, suggesting a decrease in LV filling pressure. Conclusions: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E’.ope

Left Ventricular Diastolic Function: The Link between CHA2DS2-VASc Score and Ischemic Stroke in Patients with Atrial Fibrillation

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Relationship of insulin resistance estimated by triglyceride glucose index to arterial stiffness

BACKGROUND: Insulin resistance (IR) is an important risk factor for subclinical atherosclerosis. This study evaluated the relationship between the triglyceride glucose (TyG) index, which is a simple and reliable surrogate marker for IR, and arterial stiffness. METHODS: This study included 2560 Korean subjects without a previous history of coronary artery disease, stroke, and malignancies who participated in a community-based cohort study. Arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). RESULTS: All participants were stratified into four groups based on the quartile of the TyG index. The prevalence of metabolic syndrome and diabetes significantly increased with increasing TyG index quartile. The mean baPWV was significantly different among all groups (group I [lowest]: 1421 ± 242 vs. group II: 1480 ± 244 vs. group III: 1534 ± 260 vs. group IV [highest]: 1575 ± 279 cm/s; p < 0.001). The TyG index values were correlated with baPWV (r = 0.224, p < 0.001). Multiple regression analysis showed that age (β = 0.410), male gender (β = 0.051), increased blood pressure (β = 0.266), and TyG index (β = 0.158) were associated with baPWV (p < 0.05, respectively). TyG index was independently related to baPWV in both non-diabetics and diabetics. CONCLUSIONS: The TyG index is independently associated with arterial stiffness in a relatively healthy Korean population.ope

End-Stage Renal Disease Impairs the Multidirectional Movements of the Common Carotid Artery: Assessment Using Dimensional Speckle-Tracking Carotid Strain Ultrasonography

BACKGROUND: Arterial stiffening is a major contributing factor in the development of cardiovascular disease in patients with end-stage renal disease (ESRD). However, there is no gold standard for evaluating arterial stiffness. This study aimed to evaluate the newly developed speckle-tracking carotid strain imaging method in assessing arterial stiffness in patients with ESRD. METHODS: In total, 85 patients with normal renal function (controls) and 36 with ESRD were enrolled in this single-center study. Carotid B-mode ultrasonography was performed for all patients. Arterial stiffness indices and strain parameters of the common carotid arteries were analyzed. Values were compared between the groups, and multivariate linear regression analysis was performed to assess the impact of ESRD on carotid strain. RESULTS: There were no differences in the intima-media thickness, β stiffness index, and arterial compliance, but arterial distensibility was lower, and the elastic modulus and pulse wave velocity β (PWV) were higher among patients with ESRD (all p < 0.05), whether assessed in the longitudinal or transverse plane. Both longitudinal and transverse strain rates were reduced in patients with ESRD (all p < 0.05). In multivariate analyses, ESRD independently reduced both transverse radial strain and strain rate (all p < 0.05), and the transverse circumferential strain and strain rate (p < 0.05). However, all conventional aortic stiffness indices and longitudinal strain parameters were not associated with ESRD. CONCLUSIONS: Speckle-tracking carotid strain ultrasonography was successfully performed in both normal subjects and patients with ESRD. Multidirectional carotid strain analyses may provide more value than conventional aortic stiffness indices for risk stratification in patients with ESRD.ope

Isolated 9p Duplication With der(Y)t(Y;9)(q12;p13.2) in a Male Patient With Cardiac Defect and Mental Retardation Confirmed by Chromosomal Microarray

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Characteristics of Cardiac Structural Changes in Patients with Hypertension and Atrial Fibrillation

Backgrounds: Hypertension (HTN) is a major risk factor for the development of atrial fibrillation (AF), and the presence of HTN increases the morbidity and mortality of patients with AF. HTN induces many structural and functional abnormalities of the heart. However, which structural abnormalities are primarily associated with HTN in AF patients still remains to be determined. The aim of this study was to clarify the impact of HTN on the cardiac structural changes in patients with nonvalvular AF (NV-AF). Methods: Two hundred ninety four patients (204males, age: 65.6±11.7years) with NV-AF with a preserved left ventricular (LV) systolic function were included from 6 medical centers. The clinical data was obtained and comprehensive echocardiographic examinations were performed. The patients with HTN (n=169; group 1) were compared with the patients without HTN (group 2). Results: On univariate analysis, the LV mass index (LVMI [105.0±23.0g/m2 vs. 95.7±23.5g/m2]), the left atrial volume index (LAVI [46.4±20.2ml/m2 vs. 40.5±18.9ml/m2]), the deceleration time of the early mitral inflow velocity (DT [163±39ms vs. 175±44ms]), the mitral inflow velocity (E’ [7.7±2.1cm/s vs. 8.3±2.2cm/s]) and the mitral inflow velocity to the diastolic mitral annular velocity (E/E’ [12.1±4.4 vs. 11.0±4.5]) were significanlty different between groups 1 and 2, espectively, (P<0.05 for all). However, on the multivariate analysis, the LV mass index (LVMI), which reflects LV hypertrophy (LVH), was the only factor significantly correlated with HTN in the patients with NV-AF (P<0.05). Conclusion:For patients with NV-AF with a preserved LV function, LVH was a cardiac structural abnormality that was independently associated with co-existing HTN. LVH may be related to the development and maintainence of AF and an increased cardiovascular risk in those patients.ope

Risk of new-onset diabetes among patients treated with statins according to hypertension and gender: Results from a nationwide health-screening cohort

BACKGROUND: Statins have been known to increase the risk of incident type 2 diabetes mellitus (DM); however, other factors, especially hypertension, are also associated with DM development. OBJECTIVE: We investigated whether statin use increases the risk of DM and further analyzed whether the relation between statin use and incident DM differs according to the presence of hypertension and gender. METHODS: From a nationwide health-screening cohort, 40,164 participants with total cholesterol levels >/=eve mg/dL and without pre-diagnosed DM, cardiovascular disease, or cancer, who underwent a series of regular health check-ups, were enrolled. Statin users were defined as participants who were prescribed statins more than twice during 6 months. RESULTS: There were 17,798 statin non-users and 22,366 statin users. During 7.66+/-3.21 years of follow-up, incident DM developed in 5.68% of statin non-users and 7.64% of statin users. Among the entire study population, statin use was associated with new-onset DM after adjusting for clinical risk factors. In sub-analysis according to hypertension, statin use significantly increased the risk of incident DM only in normotensive patients [hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.09 to 1.58, p = 0.004], and not in hypertensive patients (p>0.05). Furthermore, continuous statin use was strongly associated with new-onset DM in women, regardless of hypertension presence (all p0.05). CONCLUSIONS: Statin use increased the risk of new-onset DM only in normotensive patients and hypertensive women, suggesting that these groups should be more carefully monitored for the development of DM during the course of follow-up.ope

The Value of Elastic Modulus Index as a Novel Surrogate Marker for Cardiovascular Risk Stratification by Dimensional Speckle-Tracking Carotid Ultrasonography

BACKGROUND: Carotid intima media thickness (CIMT) and the presence of carotid plaque have been used for risk stratification of cardiovascular disease (CVD). To date, however, the association between multi-directional functional properties of carotid artery and CVD has not been fully elucidated. We sought to explore the multi-directional mechanics of the carotid artery in relation to cardiovascular risk. METHODS: Four hundred one patients who underwent carotid ultrasound were enrolled between January 2010 and April 2013. A high risk of CVD was defined as more than 20% of 10-year risk based on the Framingham risk score. Using a speckle-tracking technique, the longitudinal and radial movements were analyzed in the B-mode images. Peak longitudinal and radial displacements, strain and strain rate were also measured. Beta stiffness and elastic modulus index were calculated from the radial measurements. RESULTS: Of the overall sample, 13% (52) of patients comprised the high-risk group. In multivariate logistic regression, CIMT and elastic modulus index were independently associated with a high-risk of CVD {odds ratio (OR): 1.810 [95% confidence interval (CI) 1.249-2.622] and OR: 1.767 (95% CI: 1.177-2.652); p = 0.002, 0.006, respectively}. The combination of CIMT and elastic modulus index correlated with a high-risk of CVD more so than CIMT alone. CONCLUSION: The elastic modulus index of the carotid artery might serve as a novel surrogate marker of high-risk CVD. Measurement of the multi-directional mechanics of the carotid artery using the speckle tracking technique has potential for providing further information over conventional B-mode ultrasound for stratification of CVD risk.ope

Associations of changes in body mass index with all-cause and cardiovascular mortality in healthy middle-aged adults.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Sustained BMI gains were associated with reduced risk of all-cause, CV, and non-CV mortality in middle-aged healthy adults.ope