Early Detection of Pulmonary Embolism in a General Patient Population Immediately Upon Hospital Admission Using Machine Learning to Identify New, Unidentified Risk Factors: Model Development Study.

BACKGROUND: Under- or late identification of pulmonary embolism (PE)-a thrombosis of 1 or more pulmonary arteries that seriously threatens patients' lives-is a major challenge confronting modern medicine. OBJECTIVE: We aimed to establish accurate and informative machine learning (ML) models to identify patients at high risk for PE as they are admitted to the hospital, before their initial clinical checkup, by using only the information in their medical records. METHODS: We collected demographics, comorbidities, and medications data for 2568 patients with PE and 52,598 control patients. We focused on data available prior to emergency department admission, as these are the most universally accessible data. We trained an ML random forest algorithm to detect PE at the earliest possible time during a patient's hospitalization-at the time of his or her admission. We developed and applied 2 ML-based methods specifically to address the data imbalance between PE and non-PE patients, which causes misdiagnosis of PE. RESULTS: The resulting models predicted PE based on age, sex, BMI, past clinical PE events, chronic lung disease, past thrombotic events, and usage of anticoagulants, obtaining an 80% geometric mean value for the PE and non-PE classification accuracies. Although on hospital admission only 4% (1942/46,639) of the patients had a diagnosis of PE, we identified 2 clustering schemes comprising subgroups with more than 61% (705/1120 in clustering scheme 1; 427/701 and 340/549 in clustering scheme 2) positive patients for PE. One subgroup in the first clustering scheme included 36% (705/1942) of all patients with PE who were characterized by a definite past PE diagnosis, a 6-fold higher prevalence of deep vein thrombosis, and a 3-fold higher prevalence of pneumonia, compared with patients of the other subgroups in this scheme. In the second clustering scheme, 2 subgroups (1 of only men and 1 of only women) included patients who all had a past PE diagnosis and a relatively high prevalence of pneumonia, and a third subgroup included only those patients with a past diagnosis of pneumonia. CONCLUSIONS: This study established an ML tool for early diagnosis of PE almost immediately upon hospital admission. Despite the highly imbalanced scenario undermining accurate PE prediction and using information available only from the patient's medical history, our models were both accurate and informative, enabling the identification of patients already at high risk for PE upon hospital admission, even before the initial clinical checkup was performed. The fact that we did not restrict our patients to those at high risk for PE according to previously published scales (eg, Wells or revised Genova scores) enabled us to accurately assess the application of ML on raw medical data and identify new, previously unidentified risk factors for PE, such as previous pulmonary disease, in general populations.

Hospitalized patients with positive antiphospholipid antibodies who have low complement levels are at increased risk for death-a retrospective cohort study.

PURPOSE: To investigate whether low complement levels can predict worse outcomes in patients hospitalized with positive anti-phospholipid antibodies. METHODS: This was a retrospective cohort study. We obtained demographics, laboratory, and prognostic data of all consecutive patients hospitalized between 2007 and 2021, for whatever reason, with at least one positively abnormal anti-phospholipid antibody, who were also tested for complement levels (C3 or C4). We then compared the rates of long-term mortality, 1-year mortality, deep vein thrombosis, and pulmonary emboli between groups of low complement and normal complement levels. Multivariate analysis was used to control for levels of clinical and laboratory confounders. RESULTS: We identified 32,286 patients tested for anti-phospholipid antibodies. Of those patients, 6800 tested positive for at least one anti-phospholipid antibody and had a documented complement level. Significant higher mortality rates were found in the low complement group, with an odds ratio for mortality (OR 1.93 CI 1.63-2.27 p < .001). Deep vein thrombosis and pulmonary emboli rates were similar. Multivariate analysis confirmed that low complement was an independent predictor for mortality after controlling for age, sex, dyslipidemia, chronic heart failure (CHF), chronic kidney disease (CKD), and anemia. CONCLUSIONS: Our study results indicate that low complement is associated with significantly higher mortality rates in admitted patients with elevated levels of anti-phospholipid antibodies. This finding correlates with recent literature suggesting a vital role for complement activation in anti-phospholipid syndrome.

Remote Auscultation of Heart and Lungs as an Acceptable Alternative to Legacy Measures in Quarantined COVID-19 Patients-Prospective Evaluation of 250 Examinations.

The COVID-19 pandemic accelerated the assimilation of telemedicine platforms into medical practice. Nevertheless, research-based evidence in this field is still accumulating. This was a prospective, cross-sectional comparative assessment of a remote physical examination device used mainly for heart and lung digital auscultation. We analyzed usage patterns, user (physician) subjective appreciation and compared it to legacy measures. Eighteen physicians (median age 36 years (IQR 32-45): two interns, seven residents and nine senior physicians; eleven internists, five geriatricians and two pediatricians) executed over 250 remote physical examinations. Their median work duration with quarantined patients was 60 days (IQR 45-60). The median number of patients examined by a single physician was 17 (IQR 10-34). Regarding overall estimation, all participants tended to prefer the remote examination in the setting of quarantined patients (median 6, IQR 3.75-8), while no statistically significant difference was demonstrated compared to the indifference value (p = 0.122). Internists preferred tele-medical examination over non-internists, with significant differences between groups regarding heart auscultation, (median 7, (IQR 3-7) vs. median 2, (IQR 1-5, respectively)), p = 0.044. In the setting of quarantined patients, from the physicians' perspective, a digital platform for remote auscultation of heart and lungs was considered as an acceptable alternative to legacy measures.

Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center.

BACKGROUND: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020. OBJECTIVES: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel. METHODS: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented. RESULTS: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1. CONCLUSIONS: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.

Similar Outcomes in Males and Females Undergoing Surgery for Infective Endocarditis.

Background: Sex-based differences in mortality have been previously observed in patients with surgically treated infective endocarditis. We sought to evaluate the risk factors leading to this difference. Methods: A retrospective cohort from three centers in Israel comprising 376 surgically treated patients, comparing short- and long-term mortality rates and risk factors between female and male patients. Results: Compared to male patients, female patients had higher rates of hypertension (62% vs. 48%), higher rates of Gram-negative infections (20% vs. 11%), and more mitral valve replacement (55% vs. 42%). Diabetes and age were the most significant predictors for mortality and did not differ between female and male patients. In-hospital mortality rates did not differ between female and male patients (29% vs. 26%), and the difference in long-term mortality was not statistically significant (46% vs. 36% p = 0.088). Conclusions: No statistical difference was observed in short- and long-term mortality between female and male patients, most likely due to a lack of difference in the rates of important risk factors such as diabetes and age. Mortality rates decreased in the last 10 years, and a good prognosis is observed for patients surviving the initial 30 days after surgery.

Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

The Usefulness of the CHA2DS2-VASc Score to Predict Outcomes in Patients with Infective Endocarditis.

Introduction: Despite diagnostic and therapeutic advances, infective endocarditis (IE) is still associated with high mortality rates. Currently, there are no good prognostic tools for the risk assessment of patients with IE. The CHA2DS2-VASc score, used to estimate the risk of ischemic stroke in patients with non-valvular atrial fibrillation (AF), has been shown to be a powerful predictor of stroke and death in patients without known AF associated with other cardiovascular conditions. Objective: We aimed to evaluate the usefulness of the CHA2DS2-VASc score as a prognostic tool in a population of patients with IE. Methods: The Rabin Medical Center Endocarditis Team (RMCET) registry is a retrospective cohort of all patients evaluated at our center due to acute or sub-acute bacterial endocarditis. The CHA2DS2-VASc score was extracted for all patients. All-cause mortality was depicted for all patients. Results: The cohort included 330 patients with a mean age of 65.2 ± 14.7 years (70% men). During a median follow-up of 24 months [IQR 4.7-48.6], 121 (36.7%) patients died. The median CHA2DS2-VASc score was 3, and any score above 2 was associated with increased overall mortality (50.8% vs. 19.9%, p < 0.001). A multivariate model incorporating important confounders not included in the CHA2DS2-VASc model showed consistent results with a risk increase of 121% for the higher CHA2DS2-VASc score groups (HR 2.21 [CI 1.12-4.39], p = 0.023). Conclusions: IE currently has no good risk stratification models for clinical practice. The CHA2DS2-VASc score might serve as a simple and available tool to stratify risk among patients with IE.

Low Alanine Aminotransferase, as a Marker of Sarcopenia and Frailty, Is Associated with Shorter Survival Among Prostate Cancer Patients and Survivors. A Retrospective Cohort Analysis of 4064 Patients.

Background: Sarcopenia is characterized by loss of muscle mass and function and is associated with frailty, a syndrome with higher likelihood of falls, fractures, physical disability, and mortality. Both frailty and sarcopenia are known markers of shorter survival in various cancer patient populations. Low alanine aminotransferase (ALT), reflecting loss of muscle mass (sarcopenia), may be associated with greater frailty and shorter survival in multiple cancers. Objective: To assess the potential association between low ALT and shorter survival among prostate cancer (PCa) patients and survivors. Design setting and participants: This was a retrospective analysis of a historical cohort of PCa patients and survivors. Patients were defined as those still actively receiving PCa treatment, while those no longer receiving such treatment were classified as PCa survivors. Outcome measurements and statistical analysis: ALT data were obtained from results for basic biochemical blood testing carried out for patients on their first hospital admission. Patients were divided into two groups: those with ALT ≥17 IU/l and those with ALT <17 IU/l. Univariate and multivariable analyses were conducted for between-group survival comparisons. Results and limitations: We identified 9489 PCa records. The final study cohort with ALT data available included 4064 patients with ALT <40 IU/l. Of this cohort, 536 patients were actively receiving medical anticancer therapy for PCa. The mean age for the entire cohort was 74.6 yr (standard deviation 9.6) and the median ALT level was 19.28 IU/l; 1676 patients (41%) had low ALT (<17 IU/l). On univariate analysis, low ALT was associated with a 78% increase in mortality risk (95% confidence interval [CI] 1.62-1.97; p < 0.001). A sensitivity analysis of the 536 patients actively receiving medical anticancer treatment revealed that low ALT was associated with a 48% increase in mortality risk (95% CI 1.19-1.85; p = 0.001). In a multivariable model controlled for age, kidney disease, history of cerebrovascular event/transient ischemic attack, and baseline prostate-specific antigen, low ALT was still associated with a 35% increase in mortality risk (95% CI 1.12-1.63; p = 0.001). Limitations include the single-center, retrospective design. Conclusions: Low ALT, which is indicative of sarcopenia and frailty, is associated with shorter survival among PCa patients and survivors and could potentially be used for treatment personalization. Patient summary: We compared survival for prostate cancer patients and survivors according to their blood level of the protein alanine aminotransferase (ALT). Low ALT levels in the general population are associated with loss of muscle mass. We found that in our group of prostate cancer patients and survivors, the risk of death from any cause was higher for those with low ALT levels.

Low Alanine Aminotransferase as a Marker for Sarcopenia and Frailty, Is Associated with Decreased Survival of Bladder Cancer Patients and Survivors-A Retrospective Data Analysis of 3075 Patients.

BACKGROUND: Sarcopenia is characterized by the loss of muscle mass and function and is associated with frailty, a syndrome linked to an increased likelihood of falls, fractures, and physical disability. Both frailty and sarcopenia are recognized as markers for shortened survival in a number of medical conditions and in cancer patient populations. Low alanine aminotransferase (ALT) values, representing low muscle mass (sarcopenia), may be associated with increased frailty and subsequently shortened survival in cancer patients. In the current study, we aimed to assess the potential relationship between low ALT and shorter survival in bladder cancer patients and survivors. PATIENTS AND METHODS: This was a retrospective analysis of bladder cancer patients and survivors, both in and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. RESULTS: A total of 5769 bladder cancer patients' records were identified. After the exclusion of patients with no available ALT values or ALT levels above the upper normal limit, the final study cohort included 3075 patients (mean age 73.2 ± 12 years), of whom 80% were men and 1362 (53% had ALT ≤ 17 IU/L. The mean ALT value of patients within the low ALT group was 11.44 IU/L, while the mean value in the higher ALT level group was 24.32 IU/L (p < 0.001). Patients in the lower ALT group were older (74.7 vs. 71.4 years; p < 0.001), had lower BMI (25.8 vs. 27; p < 0.001), and their hemoglobin values were lower (11.7 vs. 12.6 g/dL; p < 0.001). In a univariate analysis, low ALT levels were associated with a 45% increase in mortality (95% CI 1.31-1.60, p < 0.001). In a multivariate model controlling for age, kidney function, and hemoglobin, low ALT levels were still associated with 22% increased mortality. CONCLUSIONS: Low ALT values, indicative of sarcopenia and frailty, are associated with decreased survival of bladder cancer patients and survivors and could potentially be applied for optimizing individual treatment decisions.

Low ALT, a marker of sarcopenia and frailty, is associated with shortened survival amongst myelodysplastic syndrome patients: A retrospective study.

Myelodysplastic Syndrome (MDS) is a common blood dyscrasia that mainly affects the elderly population. Several prognostic scores are available utilizing blood count variables and cytogenetic abnormalities, targeting the disease rather than the patient. Sarcopenia and frailty are associated with shortened survival rates in various disease states. Low Alanine Aminotransferase (ALT) levels are a marker of lowered muscle mass and frailty status. This study aimed to examine the correlation between low ALT levels and prognosis in MDS patients. This is a retrospective cohort study. We obtained the demographic, clinical, and laboratory data of patients in a tertiary hospital. Univariate and multivariate models were used to investigate the potential relationship between low ALT level and survival. The final study included 831 patients (median age 74.3 years, Interquartile range 65.6-81.8), and 62% were males. The median ALT level was 15 international units (IU)/L and 233 patients (28%) had low ALT levels (<12 IU/L). Univariate analysis showed that low ALT levels were associated with a 25% increase in mortality (95% confidence interval [CI]: 1.05-1.50, P = .014). A multivariate model controlling for age, sex, body mass index, hemoglobin and albumin concentrations, and low ALT levels was still significantly associated with increased mortality (hazard ratio [HR] = 1.25, 95% CI: 1.01-1.56, P = .041). Low ALT levels were associated with increased mortality among patients with MDS. Impact: Using ALT as a frailty metric may allow patient-centered, personalized care in this patient population. A low ALT level reflects the pre-morbid robustness of patients and is not intended to replace disease-centered characteristics.

Do low levels of alanine aminotransferase, a baseline marker of sarcopenia and frailty, associate with worse clinical outcomes among hospitalized COVID-19 patients? A Retrospective Cohort Study.

Objectives: COVID-19 geoperdize lives. Not all the risk factors for negative outcomes are known. Sarcopenia and frailty are common, negatively affecting clinical outcomes. Studies have shown that sarcopenia and frailty are associated with worse outcomes. Our objective was to examine whether low ALT (Alanine-aminotranferase), a surrogate marker for sarcopenia, is associated with worse clinical outcomes among hospitalized COVID-19 patients. Methods: We reviewed cases of COVID-19 in a tertiary hospital, during three COVID-19 waves and examined correlations between ALT and mortality using crude, univariate and multivariate analysis for age, gender, hypertension, Chronic obstructive pulmonary disease and Congestive heart failure. Results: 357 patients were included in this analysis. Median age was 69, 54% were males. Median ALT was 19 IU/L. During follow-up, 73 (20%) died. Patients with low ALT were more likely to die (HR 1.82, 95% CI 1.06-3.09, P=0.028). Other predictors for mortality were low albumin, background COPD, dyslipidemia, dementia, and malignancy. The multivariate analysis showed that low ALT was still an independent predictor of poor prognosis (HR 1.7, 95% CI 1.0-2.9, P=0.049). Conclusions: In our analysis of COVID-19 patients, low ALT levels were independently associated with increased risk of mortality, both as standalone and when incorporated into a multivariate analysis.

Atrial fibrillation in young hospitalized patients: Clinical characteristics, predictors of new onset, and outcomes.

BACKGROUND: Atrial fibrillation (AF) in young adults is an uncommon and not well studied entity. METHODS: Consecutive patients aged 18-45 years admitted to internal or cardiology services in a large tertiary medical center (January 1, 2009 through December 31, 2019) were included. Clinical, electrocardiographic, and echocardiographic data were compared between patients with and without AF at baseline. Predictors of new-onset AF in the young were identified using multivariate Cox regression model among patients free of baseline AF. RESULTS: Final cohort included 16,432 patients with median age of 34 (IQR 26-41) years of whom 8914 (56 %) were men. Patients with AF at baseline (N = 366; 2 %) were older, more likely to be men, and had higher proportion of comorbidities and electrocardiographic conduction disorders. Male sex, increased age, obesity, heart failure, congenital heart disease (CHD) and the presence of left or right bundle branch block were all independently associated with baseline AF in a multivariate model (p < 0.001 for all). Sub-analysis of 10,691 (98 %) patients free of baseline AF identified 85 cases of new-onset AF during a median follow up of 3.5 (IQR 1.5-6.5) years. Multivariate model identified increased age, heart failure, and CHD as independent predictors of new-onset AF. Finally, the CHARGE-AF risk score outperformed the CHA2DS2-VASc score in AF prediction [AUC of ROC 0.75 (0.7-0.8) vs. 0.56 (0.48-0.65)]. CONCLUSIONS: AF among hospitalized young adults is not rare. Screening for new-onset AF in young post hospitalization patients may be guided by specific clinical predictors and the CHARGE-AF risk score.

Sarcopenia as Manifested by L3SMI Is Associated with Increased Long-Term Mortality amongst Internal Medicine Patients-A Prospective Cohort Study.

Background: Sarcopenia and Frailty are syndromes that affect the clinical outcomes of patients suffering from a wide range of diseases. The use of Computed Tomography (CT) is well established for Sarcopenia evaluation via estimation of the Skeletal Muscle Index (SMI) at the level of the third lumbar vertebra (L3SMI). Nevertheless, the association of more readily available biomarkers of Sarcopenia and clinical outcomes is desired. Recent studies have associated low Alanine amino-transferase ALT (SGPT) levels with Sarcopenia and frailty. The current study aimed to establish the association between low L3SMI and the aforementioned indices of Sarcopenia, frailty and poor clinical outcomes. Methods: A cohort study of patients admitted to the internal medicine department at a tertiary medical center. Sarcopenia was determined as L3SMI, lower than 53 cm2/m2 in men and 41 cm2/m2 in women. Clinical and mortality data was collected from the medical record. Results: Of the 187 patients recruited (mean age 70.4 ± 9.2, 59% males), 116 (62%) had Sarcopenia, based on L3SMI values. Sarcopenic patients were older, predominantly male, had lower BMI, lower mid-arm muscle circumference (MAMC) and low ALT values upon admission. L3SMI values significantly correlated with age and MAMC among males (R = −0.38, p < 0.001, R = 0.35, p < 0.001, respectively). Sarcopenia was associated with higher, one-year mortality (HR = 2.60, 95% CI 1.06−6.37, p = 0.036) and shorter all-time survival (HR = 2.91, 95% CI 1.35−6.29, p = 0.007). The association with all-time survival remained after adjusting for age and sex (HR = 2.38, 95% CI 1.07−5.29, p = 0.034). Conclusion: As defined by low L3SMI value, Sarcopenia is a poor prognostic factor for the general internal ward patient population. As part of personalized medicine, physicians may benefit from measuring L3SMI value, as indicated by commonly performed CT scans, to objectively assess their patient's risk of suffering from Sarcopenia and frailty-associated complications.

Developing and validating a machine learning prognostic model for alerting to imminent deterioration of hospitalized patients with COVID-19.

Our study was aimed at developing and validating a new approach, embodied in a machine learning-based model, for sequentially monitoring hospitalized COVID-19 patients and directing professional attention to patients whose deterioration is imminent. Model development employed real-world patient data (598 prediction events for 210 patients), internal validation (315 prediction events for 97 patients), and external validation (1373 prediction events for 307 patients). Results show significant divergence in longitudinal values of eight routinely collected blood parameters appearing several days before deterioration. Our model uses these signals to predict the personal likelihood of transition from non-severe to severe status within well-specified short time windows. Internal validation of the model's prediction accuracy showed ROC AUC of 0.8 and 0.79 for prediction scopes of 48 or 96 h, respectively; external validation showed ROC AUC of 0.7 and 0.73 for the same prediction scopes. Results indicate the feasibility of predicting the forthcoming deterioration of non-severe COVID-19 patients by eight routinely collected blood parameters, including neutrophil, lymphocyte, monocyte, and platelets counts, neutrophil-to-lymphocyte ratio, CRP, LDH, and D-dimer. A prospective clinical study and an impact assessment will allow implementation of this model in the clinic to improve care, streamline resources and ease hospital burden by timely focusing the medical attention on potentially deteriorating patients.

Low ALT levels are associated with poor outcomes in acute coronary syndrome patients in the intensive cardiac care unit.

BACKGROUND: Frailty is an underrecognized and important entity that bears worse prognosis. Although low serum alanine aminotransferase (ALT) can serve as a novel marker of frailty, its use was never assessed in acute coronary syndrome (ACS) patients. METHODS: A retrospective analysis of hospitalized ACS patients in the intensive cardiac care unit (ICCU)between 1/5/2011 and 1/12/2020 at a single tertiary medical center. RESULTS: The study included 3956 patients after excluding patients with ALT >40 IU/L, cirrhosis, and missing data, followed for a medianduration of 47 months (IQR 20-77).Patients were stratified into two groups based on their first ALT measurement within the index hospitalization: low-normal ALT group (ALT ≤10 IU/L) vs. high-normal ALT group (ALT >10 IU/L). Patients with ALT≤10 IU/L were older (mean age 71 years vs. 65 years, p<0.001), presented more frequently with non-ST elevation myocardial infarction (66.4% vs. 53.2%, p< 0.001), had higher rates of comorbiditiesat baseline, and had a lower Norton score upon admission. Hospitalization length was longer in the low-normal ALT group (p< 0.001). Although the in-hospital mortality rate was similar between the groups (0.9% vs. 0.7%, p = 0.99), long-termmortality was significantly higher in the low-normal ALT group (22.7% vs. 7.9%, p< 0.001). In a multivariate regression model ALT ≤10 IU/l was associated with increased mortality (HR 2.1, 95% CI 1.46-3). CONCLUSIONS: Lower serum ALT is associated with worse outcomes in ACS patients admitted to the ICCU.

Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure.

OBJECTIVE: Investigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation. METHODS: Consecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012-2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up. RESULTS: Final cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64). CONCLUSIONS: Levosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.

The Association of Moderate Aortic Stenosis with Poor Survival Is Modified by Age and Left Ventricular Function: Insights from SHEBAHEART Big Data.

BACKGROUND: Data on the independent association of moderate aortic stenosis (AS) with excess mortality, even when it does not progress to severe AS, are limited. The aims of this study were to evaluate the association of moderate AS with poor survival and to identify clinically important modifiers of that association. METHODS: Consecutive patients who underwent echocardiographic evaluation between 2007 and 2019 were included. All-cause mortality and cancer data were available for all patients from national registries. Cox regression survival models were applied, with censoring of patients who developed metastatic cancer, developed more than moderate AS, or underwent aortic valve intervention during follow-up. RESULTS: The study population included 92,622 patients. There were 2,202 patients (2%) with moderate AS, with a median age of 79 years (interquartile range, 70-85 years), of whom 1,254 (57%) were men. During median follow-up of 5 years (interquartile range, 3-8 years), 19,712 patients (21%) died. The cumulative probability of death at 5 years was higher for patients with moderate AS (46% vs 18%, respectively, log-rank P < .001). Propensity score matching analysis (n = 2,896) that included clinical, laboratory, and echocardiographic predictors of poor survival demonstrated that compared with patients with mild or less AS, those with moderate AS were 17% more likely to die (95% CI, 1.04-1.30; P = .007). Moreover, the model showed that the moderate AS-associated risk was ejection fraction and age dependent, with a more pronounced association among nonoctogenarian patients (P for interaction = .001) and those with reduced ejection fractions (P for interaction = .016). CONCLUSIONS: Moderate AS is independently associated with excess mortality, even when it does not progress to severe AS. The associated risk is more pronounced among patients with reduced ejection fractions and those <80 years of age.

Assessing the Usability of a Novel Wearable Remote Patient Monitoring Device for the Early Detection of In-Hospital Patient Deterioration: Observational Study.

BACKGROUND: Patients admitted to general wards are inherently at risk of deterioration. Thus, tools that can provide early detection of deterioration may be lifesaving. Frequent remote patient monitoring (RPM) has the potential to allow such early detection, leading to a timely intervention by health care providers. OBJECTIVE: This study aimed to assess the potential of a novel wearable RPM device to provide timely alerts in patients at high risk for deterioration. METHODS: This prospective observational study was conducted in two general wards of a large tertiary medical center. Patients determined to be at high risk to deteriorate upon admission and assigned to a telemetry bed were included. On top of the standard monitoring equipment, a wearable monitor was attached to each patient, and monitoring was conducted in parallel. The data gathered by the wearable monitors were analyzed retrospectively, with the medical staff being blinded to them in real time. Several early warning scores of the risk for deterioration were used, all calculated from frequent data collected by the wearable RPM device: these included (1) the National Early Warning Score (NEWS), (2) Airway, Breathing, Circulation, Neurology, and Other (ABCNO) score, and (3) deterioration criteria defined by the clinical team as a "wish list" score. In all three systems, the risk scores were calculated every 5 minutes using the data frequently collected by the wearable RPM device. Data generated by the early warning scores were compared with those obtained from the clinical records of actual deterioration among these patients. RESULTS: In total, 410 patients were recruited and 217 were included in the final analysis. The median age was 71 (IQR 62-78) years and 130 (59.9%) of them were male. Actual clinical deterioration occurred in 24 patients. The NEWS indicated high alert in 16 of these 24 (67%) patients, preceding actual clinical deterioration by 29 hours on average. The ABCNO score indicated high alert in 18 (75%) of these patients, preceding actual clinical deterioration by 38 hours on average. Early warning based on wish list scoring criteria was observed for all 24 patients 40 hours on average before clinical deterioration was detected by the medical staff. Importantly, early warning based on the wish list scoring criteria was also observed among all other patients who did not deteriorate. CONCLUSIONS: Frequent remote patient monitoring has the potential for early detection of a high risk to deteriorate among hospitalized patients, using both grouped signal-based scores and algorithm-based prediction. In this study, we show the ability to formulate scores for early warning by using RPM. Nevertheless, early warning scores compiled on the basis of these data failed to deliver reasonable specificity. Further efforts should be directed at improving the specificity and sensitivity of such tools. TRIAL REGISTRATION: ClinicalTrials.gov NCT04220359; https://clinicaltrials.gov/ct2/show/NCT04220359.

Hypokinetic hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis.

AIMS: To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. METHODS AND RESULTS: Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing-risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all-cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1-10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. CONCLUSIONS: Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.