Interpretable estimation of the risk of heart failure hospitalization from a 30-second electrocardiogram

Survival modeling in healthcare relies on explainable statistical models; yet, their underlying assumptions are often simplistic and, thus, unrealistic. Machine learning models can estimate more complex relationships and lead to more accurate predictions, but are non-interpretable. This study shows it is possible to estimate hospitalization for congestive heart failure by a 30 seconds single-lead electrocardiogram signal. Using a machine learning approach not only results in greater predictive power but also provides clinically meaningful interpretations. We train an eXtreme Gradient Boosting accelerated failure time model and exploit SHapley Additive exPlanations values to explain the effect of each feature on predictions. Our model achieved a concordance index of 0.828 and an area under the curve of 0.853 at one year and 0.858 at two years on a held-out test set of 6,573 patients. These results show that a rapid test based on an electrocardiogram could be crucial in targeting and treating high-risk individuals.Comment: 4 pages, 4 figure

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients:Dabigatran versus rivaroxaban

Abstract Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality

Differential Presentations of Arterial Thromboembolic Events Between Venous Thromboembolism and Atrial Fibrillation Patients

Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) share several risk factors related to arterial thromboembolism. No study has reported the differential contribution to arterial thromboembolic events and mortality between these two conditions in the same population. We therefore assessed the differential arterial thromboembolic events between AF and VTE. Methods: We included AF and VTE national cohorts derived from Taiwan National Health Insurance Research Database between 2001 and 2013. The eligible population was 314,861 patients in the AF cohort and 41,102 patients in the VTE cohort. The primary outcome was arterial thromboembolic events, including ischemic stroke, extracranial arterial thromboembolism (ECATE) and myocardial infarction (MI). Secondary outcomes were all-cause mortality and cardiovascular death. Results: After a 1:1 propensity matching, 32,688 patients in either group were analyzed. The risk of arterial thromboembolic events was lower in the VTE cohort than that in the AF cohort (subdistribution hazard ratio [SHR], 0.60; 95% confidence interval [CI], 0.57–0.62). The risk of ischemic stroke (SHR, 0.44; 95% CI, 0.42–0.46) and MI (SHR, 0.80; 95% CI, 0.72–0.89) were lower in the VTE cohort, while the risk of ECATE (SHR, 1.23; 95% CI, 1.14–1.33; particularly lower extremities) was higher in the VTE cohort. All-cause mortality rate was higher in the VTE cohort (HR, 1.18; 95% CI, 1.15–1.21) while the risk of cardiovascular death was lower in the VTE cohort (HR, 0.96; 95% CI, 0.93–0.995). Conclusions: Patients with AF had higher risks of arterial thromboembolic events compared to patients with VTE, despite having risk factors in common. The VTE cohort had higher risks of all-cause mortality and ECATE, particularly lower extremity events, compared to AF patients. The differential manifestations of thromboembolism sequelae and mortality between AF and VTE patients merit further investigation

Redefining Diastolic Dysfunction Grading Combination of E/A ≤0.75 and Deceleration Time >140 ms and E/ε′ ≥10

AbstractObjectivesThis study sought to examine left atrial (LA) mechanics and the prognostic impact of patients with echocardiographic findings of E/A ratio ≤0.75, deceleration time (DcT) of mitral E-wave >140 ms, but E/ε′ ≥10.BackgroundTraditional diastolic dysfunction (DD) grading system could not classify every patient into a specific group. We considered the group of patients with E/A ≤0.75, DcT >140 ms, but E/ε′ ≥10 (proposed new DD grade) as a new group in the DD grading system.MethodsA total of 1,362 consecutive patients were stratified according to the new DD grading system, and the LA volumes, strain, and strain rates were measured by 2-dimensional speckle-tracking analysis. All patients were followed up to determine cardiac death and major adverse cardiac events.ResultsAn E/A ≤0.75, DcT >140 ms, but E/ε′ ≥10 was observed in 227 patients (17%). LA volumes in patients with the new DD grade were between those of the impaired relaxation group and the pseudonormal group. LA strain of the new DD grade was similar to that of the pseudonormal group, whereas LA booster function was preserved as in the impaired relaxation group. During a mean follow-up of 3.0 ± 1.1 years, 25 patients had cardiac death and 61 had major adverse cardiac events. Event-free survival for major adverse cardiac events of the new DD grade was worse than that of the impaired relaxation group but similar to that of the pseudonormal group.ConclusionsThe new DD grade is frequently observed and has a prognosis similar to that of the pseudonormal group but significantly worse than that of the impaired relaxation group. However, LA booster function was maintained at the expense of LA volume enlargement. Thus, the new grade should be a distinct entity for routine DD grading

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Early Detection of Left Ventricular Diverticulum by Transthoracic Echocardiography

Left ventricular diverticulum is a very rare entity to be found in adults. Noninvasive echocardiography can offer useful information prior to contrast-enhanced computer tomography or invasive angiography. We evaluated a patient with left ventricular apical diverticulum but complained no symptoms. Transthoracic echocardiography demonstrated a outpouching at left ventricle apex. A 640-slice computed tomography later confirmed the left ventricular diverticulum

Impact of Sodium–Glucose Co-Transporter 2 Inhibitors on Cardiac Protection

Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors

Autophagy in Chronic Kidney Diseases

Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, diabetic nephropathies, and polycystic kidney diseases. Oxidative stress, inflammation, and mitochondrial dysfunction, which are implicated as important mechanisms underlying many kidney diseases, modulate the autophagy activation and inhibition and lead to cellular recycling dysfunction. Abnormal autophagy function can induce loss of podocytes, damage proximal tubular cells, and glomerulosclerosis. After acute kidney injuries, activated autophagy protects tubular cells from apoptosis and enhances cellular regeneration. Patients with chronic kidney diseases have impaired autophagy that cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter the autophagy signaling, by which the mechanistic insights of the drugs are revealed, thus providing the unique opportunity to manage the nephrotoxicity of these drugs. In this review, we summarize the current concepts of autophagy and its molecular aspects in different kidney cells pathophysiology. We also discuss the current evidence of autophagy in acute kidney injury, chronic kidney disease, toxic effects of drugs, and aging kidneys. In addition, we examine therapeutic possibilities targeting the autophagy system in kidney diseases

Normal range of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography

<div><p>Background</p><p>Newer 2D strain software has a potential to assess layer-specific strain. However, normal reference values for layer-specific strain have not been established. We aimed to establish the normal ranges of layer-specific longitudinal and circumferential strain (endocardial global longitudinal strain (GLS), transmural GLS, epicardial GLS, endocardial global circumferential strain (GCS), transmural GCS, and epicardial GCS).</p><p>Methods and results</p><p>We retrospectively analyzed longitudinal and circumferential strain parameters in 235 healthy subjects, with use of layer-specific 2D speckle tracking software (GE). The endocardial strain/epicardial strain (Endo/Epi) ratio was also measured to assess the strain gradient across the myocardium. The endocardial, transmural, and epicardial GLS values and the Endo/Epi ratio in the normal subjects were -23.1±2.3, -20.0±2.0, -17.6±1.9, and 1.31±0.07, respectively. The corresponding values of GCS were -28.5±3.0, -20.8±2.3, -15.3±2.0, and 1.88±0.17, respectively. The layer-specific global strain parameters exhibited no age dependency but did exhibit gender dependency except for endocardial GCS. A subgroup analysis revealed that basal and middle levels of endocardial LS was decreased in the middle and elderly aged group. However, apical endocardial LS was preserved even in the elderly subjects.</p><p>Conclusions</p><p>We proposed normal reference values for layer-specific strain based on both age and gender. This detailed strain analysis provides layer-oriented information with the potential to characterize abnormal findings in various cardiovascular diseases.</p></div