Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors have been demonstrated to promote reverse cardiac remodeling in people with diabetes or heart failure. Although it has been theorized that sodium-glucose cotransporter 2 inhibitors might afford similar benefits in people without diabetes or prevalent heart failure, this has not been evaluated. We sought to determine whether sodium-glucose cotransporter 2 inhibition with empagliflozin leads to a decrease in left ventricular (LV) mass in people without type 2 diabetes or significant heart failure. METHODS: Between April 2021 and January 2022, 169 individuals, 40 to 80 years of age, without diabetes but with risk factors for adverse cardiac remodeling were randomly assigned to empagliflozin (10 mg/d; n=85) or placebo (n=84) for 6 months. The primary outcome was the 6-month change in LV mass indexed (LVMi) to baseline body surface area as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and LV end-systolic volumes indexed to baseline body surface area and LV ejection fraction. RESULTS: Among the 169 participants (141 men [83%]; mean age, 59.3±10.5 years), baseline LVMi was 63.2±17.9 g/m2 and 63.8±14.0 g/m2 for the empagliflozin- and placebo-assigned groups, respectively. The difference (95% CI) in LVMi at 6 months in the empagliflozin group versus placebo group adjusted for baseline LVMi was -0.30 g/m2 (-2.1 to 1.5 g/m2; P=0.74). Median baseline (interquartile range) NT-proBNP (N-terminal-pro B-type natriuretic peptide) was 51 pg/mL (20-105 pg/mL) and 55 pg/mL (21-132 pg/mL) for the empagliflozin- and placebo-assigned groups, respectively. The 6-month treatment effect of empagliflozin versus placebo (95% CI) on blood pressure and NT-proBNP (adjusted for baseline values) were -1.3 mm Hg (-5.2 to 2.6 mm Hg; P=0.52), 0.69 mm Hg (-1.9 to 3.3 mm Hg; P=0.60), and -6.1 pg/mL (-37.0 to 24.8 pg/mL; P=0.70) for systolic blood pressure, diastolic blood pressure, and NT-proBNP, respectively. No clinically meaningful between-group differences in LV volumes (diastolic and systolic indexed to baseline body surface area) or ejection fraction were observed. No difference in adverse events was noted between the groups. CONCLUSIONS: Among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, sodium-glucose cotransporter 2 inhibition with empagliflozin did not result in a meaningful reduction in LVMi after 6 months. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04461041.

Development and Validation of a Novel Risk Score for All-Cause Mortality Risk Stratification Prior to Permanent Pacemaker Implantation in Octogenarians or Older.

Background and Objectives: The demand for permanent pacemaker (PPM) implantation for extremely old patients is increasing. Prior to implanting PPMs, life expectancy evaluation is essential but difficult. We aimed to develop and validate a scoring system for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80. Materials and Methods: A total of 210 patients aged ≥80 who received PPM implantation were included. Multivariable analysis was performed to assess the effects of different variables on all-cause mortality in a derivation cohort (n = 100). We developed the MELODY score for stratifying all-cause mortality prior to PPM implantation and tested the scoring system in a validation cohort (n = 102). Results: After 4.0 ± 2.7 years of follow-up, 54 patients (54%) had died. The 0.5-, 1- and 2-year all-cause mortality rates were 7%, 10% and 24%, respectively. The MELODY score based on body mass index <21 kg/m2 (HR: 2.21, 95% CI: 1.06-4.61), estimated glomerular filtration rate <30 mL/min/1.73 m2 (3.35, 1.77-6.35), length of hospitalization before PPM implantation >7 days (1.87, 1.02-3.43) and dyspnea as the major presenting symptom (1.90, 1.03-3.50) successfully distinguished patients at high risk of mortality. Patients with MELODY scores ≥3 had a higher risk of mortality compared to those with MELODY scores <3 (8.49, 4.24-17.00). The areas under the receiver operating characteristic curves in predicting 0.5, 1 and 2 years mortality rates were 0.86, 0.81 and 0.74, respectively. The predictive value of the model was confirmed in a validation cohort. Conclusions: The novel scoring system is a simple and effective tool for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80.

Stress Hyperphenylalaninemia Is Associated With Mortality in Cardiac ICU: Clinical Factors, Genetic Variants, and Pteridines.

OBJECTIVES: Hyperphenylalaninemia predicts poor outcomes in patients with cardiovascular disease. However, the prognostic value and factors associated with stress hyperphenylalaninemia (SHP) were unknown in critical patients in the cardiac ICU. DESIGN: Prospective observational study. SETTING: Single-center, cardiac ICU in Taiwan. PATIENTS: Patients over 20 years old with Acute Physiology And Chronic Health Evaluation II scores greater than or equal to 15 and/or ventilatory support in the cardiac ICU. INTERVENTIONS: We measured plasma phenylalanine levels serially during patients' stays in the ICU to investigate their prognostic value for 90-day mortality. Gene array was performed to identify genetic polymorphisms associated with SHP (phenylalanine level ≥ 11.2 µmol/dL) and to develop a Genetic Risk Score (GRS). We analyzed the associations between SHP and clinical factors and genetic variants and identified the correlation between pteridines and genetic variants. MEASUREMENTS AND MAIN RESULTS: The study enrolled 497 patients. Increased phenylalanine concentration was independently associated with increased mortality risk. Patients with SHP had a higher mortality risk compared with those without SHP (log rank = 41.13; p < 0.001). SHP was associated with hepatic and renal dysfunction and with genetic polymorphisms on the pathway of tetrahydrobiopterin (BH4) synthesis (CBR1 and AKR1C3) and recycling (PCBD2). Higher GRSs were associated with lower BH4 bioavailability in response to stress ( p < 0.05). In patients without SHP at baseline, those with GRSs gretaer than or equal to 2 had a higher frequency of developing SHP during the ICU stay (31.5% vs 16.1%; p = 0.001) and a higher mortality risk ( p = 0.004) compared with those with GRSs less than 2. In patients with SHP at baseline, genetic variants did not provide additional prognostic value. CONCLUSIONS: SHP in patients admitted to the ICU was associated with a worse prognosis. In patients without SHP, genetic polymorphisms associated with SHP measured using a GRS of greater than or equal to 2 was associated with the subsequent SHP and higher mortality risk.

Decreases in Circulating Concentrations of Short-Chain Acylcarnitines are Associated with Systolic Function Improvement After Decompensated Heart Failure.

Impaired fatty acid metabolism is associated with heart failure (HF) prognosis. However, specific changes in acylcarnitine profiles and their potential clinical value have not been well explored in patients recovering from acute decompensation.This study recruited 79 HF patients hospitalized because of acute decompensation with a left ventricular ejection fraction (LVEF) of < 40% and 51 normal controls. Patients were dichotomized into two groups, namely, the "improved (IMP) " and the "non-improved (NIMP) " groups, as defined by the changes in LVEF from baseline to 12 months after discharge. Mass spectrometry was used to quantify the acylcarnitine concentrations at baseline and 6 and 12 months after discharge. The IMP and NIMP groups contained 42 and 37 patients, respectively. At baseline, HF patients had higher plasma concentrations of specific long-, medium-, and short-chain acylcarnitines compared to normal controls. From baseline to 12 months post-discharge, the IMP group showed significant decreases in long- and short-chain acylcarnitine concentrations, but significant increases in medium-chain acylcarnitines. In the NIMP group, none of the acylcarnitines significantly decreased, and significant increases were noted in long-, medium-, and short-chain acylcarnitines. Generalized estimating equations demonstrated that nine acylcarnitines could discriminate the IMP group from the NIMP group, including three long-chain (C18:1, C16, and C16:1) and six short-chain acylcarnitines (C5, C5-OH, C4, C4:1-DC, C3, and C2). After adjusting for age, the six short-chain acylcarnitines remained significant. Changes in short-chain acylcarnitine profiles are independently associated with the improvement in cardiac systolic function after acute decompensation.

Predictors of long-term survival prior to permanent pacemaker implantation in octogenarians or older.

BACKGROUND: There is an increased need for permanent pacemaker (PPM) implantation for older patients with multiple comorbidities. The current guidelines recommend that, before implanting PPM, clinicians should discuss life expectancy with patients and their families as part of the decision-making process. However, estimating individual life expectancy is always a challenge. AIMS: We investigated predictors of long-term survival prior to PPM implantation in patients aged 80 or older. METHODS AND RESULTS: From September 2004 to September 2015, 100 patients aged ≥ 80 years who received PPM implantation were included for retrospective survival analysis. The end point was all-cause mortality. Follow-up duration was 4.0 ± 2.7 years. By the end of the study, 54 patients (54%) had died. Of the 54 who died, 40 patients (74.1%) died of non-cardiac causes. Their survival rates at 1, 2, 3, 5, and 7 years were 90%, 76%, 54%, 32%, and 16%, respectively. Patients with a longer length of hospital stay before PPM implantation (LOS-B) [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.02-1.05, p < 0.001], estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 (HR 4.07, 95% CI 1.95-8.52, p < 0.001), body mass index (BMI) < 21 kg/m2 (HR 2.50, 95% CI 1.16-5.39, p = 0.02), and dyspnea as the major presenting symptom (HR 2.88, 95% CI 1.27-6.55, p = 0.01) were associated with lower cumulative survival. CONCLUSIONS: Longer LOS-B, lower eGFR and BMI, and dyspnea as the major presenting symptom are pre-PPM implantation predictors of long-term survival in patients aged 80 or older.

Aliskiren attenuates the effects of interleukin-6 on endothelial nitric oxide synthase and caveolin-1 in human aortic endothelial cells.

Renin inhibitors enhance endothelial nitric oxide synthase (eNOS) bioavailability and have protective effects on endothelial function and atherosclerotic changes. This study was designed to investigate whether aliskiren attenuates the effects of interleukin-6 (IL-6) on eNOS and the eNOS-caveolin-1 interaction in human aortic endothelial cells (HAECs). In this study, we examined the effects of pretreatment with aliskiren on the changes of IL-6-induced expression and activation of eNOS and caveolin-1 in cultured HAECs. IL-6 inhibited and aliskiren increased the phosphorylation of eNOS at Ser1177; however, eNOS protein and mRNA expression were not changed. Pretreatment with aliskiren attenuated the inhibitory effects of IL-6 on eNOS phosphorylation and nitric oxide production. IL-6 increased the phosphorylation of caveolin-1 at Tyr14 without affecting the caveolin-1 protein and mRNA expression. Pretreatment with aliskiren attenuated the effects of IL-6 on caveolin-1 phosphorylation. The binding of eNOS and caveolin-1, as determined by a co-immunoprecipitation assay, was increased by IL-6 treatment and decreased by aliskiren pretreatment. Furthermore, treatment with short interfering RNA of the extracellular signal-regulated kinase gene reversed the effects of IL-6 and aliskiren on eNOS and caveolin-1. In conclusion, aliskiren attenuates the inhibitory effects of IL-6 on eNOS phosphorylation and nitric oxide production and IL-6 induced caveolin-1 phosphorylation. In addition, aliskiren reverses the effects of IL-6 on the eNOS-caveolin-1 interaction.

Differences of left ventricular systolic deformation in hypertensive patients with and without apical hypertrophic cardiomyopathy.

BACKGROUND: We tested the hypothesis that the apical myocardial mechanics differ from those of other ventricular segments in hypertensive patients with and without apical hypertrophic cardiomyopathy (ApHCM). METHODS: We retrospectively studied hypertensive patients with and without ApHCM. Left ventricular longitudinal, circumferential, and radial strains were examined by two-dimensional speckle-tracking echocardiography at the basal, middle, and apical walls of the parasternal short-axis and apical 2-, 3- and 4-chamber views. RESULTS: Fourteen consecutive patients with hypertension and ApHCM and 14 patients with hypertension without ApHCM were studied. Lower mitral annular peak systolic velocity and greater diastolic dysfunction were present in hypertensive patients with ApHCM than in hypertensive patients without ApHCM. Compared with hypertensive patients without ApHCM, hypertensive patients with ApHCM had significantly lower apical longitudinal (-13.9% vs -21.9%, p = 0.010) and radial strains (4.4% vs 11.5%, p = 0.017) without the base-to-apex gradient. The global longitudinal (-15.6% vs -18.8%, p = 0.027) and circumferential strains (-16.1% vs -19.2%, p = 0.019) were significantly lower in hypertensive patients with ApHCM than in hypertensive patients without ApHCM. Among systolic parameters, the global longitudinal strain was independently associated with hypertension with ApHCM (odds ratio, 1.457; 95% confidence interval, 1.002-2.119; p = 0.049). CONCLUSIONS: Reduced apical longitudinal and radial strains without a base-to-apex gradient were present in hypertensive patients with ApHCM. The global longitudinal strain was independently associated with ApHCM in hypertensive patients.

Combining Phenylalanine and Leucine Levels Predicts 30-Day Mortality in Critically Ill Patients Better than Traditional Risk Factors with Multicenter Validation.

In critically ill patients, risk scores are used; however, they do not provide information for nutritional intervention. This study combined the levels of phenylalanine and leucine amino acids (PLA) to improve 30-day mortality prediction in intensive care unit (ICU) patients and to see whether PLA could help interpret the nutritional phases of critical illness. We recruited 676 patients with APACHE II scores ≥ 15 or intubated due to respiratory failure in ICUs, including 537 and 139 patients in the initiation and validation (multicenter) cohorts, respectively. In the initiation cohort, phenylalanine ≥ 88.5 µM (indicating metabolic disturbance) and leucine < 68.9 µM (indicating malnutrition) were associated with higher mortality rate. Based on different levels of phenylalanine and leucine, we developed PLA scores. In different models of multivariable analyses, PLA scores predicted 30-day mortality independent of traditional risk scores (p < 0.001). PLA scores were then classified into low, intermediate, high, and very-high risk categories with observed mortality rates of 9.0%, 23.8%, 45.6%, and 81.8%, respectively. These findings were validated in the multicenter cohort. PLA scores predicted 30-day mortality better than APACHE II and NUTRIC scores and provide a basis for future studies to determine whether PLA-guided nutritional intervention improves the outcomes of patients in ICUs.

Prediction of survival time after terminal extubation: the balance between critical care unit utilization and hospice medicine in the COVID-19 pandemic era.

BACKGROUND: We established 1-h and 1-day survival models after terminal extubation to optimize ventilator use and achieve a balance between critical care for COVID-19 and hospice medicine. METHODS: Data were obtained from patients with end-of-life status at terminal extubation from 2015 to 2020. The associations between APACHE II scores and parameters with survival time were analyzed. Parameters with a p-value ≤ 0.2 in univariate analysis were included in multivariate models. Cox proportional hazards regression analysis was used for the multivariate analysis of survival time at 1 h and 1 day. RESULTS: Of the 140 enrolled patients, 76 (54.3%) died within 1 h and 35 (25%) survived beyond 24 h. No spontaneous breathing trial (SBT) within the past 24 h, minute ventilation (MV) ≥ 12 L/min, and APACHE II score ≥ 25 were associated with shorter survival in the 1 h regression model. Lower MV, SpO2 ≥ 96% and SBT were related to longer survival in the 1-day model. Hospice medications did not influence survival time. CONCLUSION: An APACHE II score of ≥ 25 at 1 h and SpO2 ≥ 96% at 1 day were strong predictors of disposition of patients to intensivists. These factors can help to objectively tailor pathways for post-extubation transition and rapidly allocate intensive care unit resources without sacrificing the quality of palliative care in the era of COVID-19. Trial registration They study was retrospectively registered. IRB No.: 202101929B0.

Non-invasive cardiac index monitoring during cardiopulmonary functional testing provides additional prognostic value in patients after acute heart failure.

The prognostic value of parameters derived from a cardiopulmonary exercise test (CPET) is well established in patients stabilized after acute heart failure (HF). Under multidisciplinary disease management, this study sought to test whether noninvasive cardiac output (CO) monitoring (NICOM) during the CPET provides additional prognostic value. In total, 131 patients stabilized after acute HF agreed to undergo the CPET with NICOM. Outcome follow-up focused on composite events of death and HF-related rehospitalization. Patients with a peak cardiac index (CI) of ≤ 4.5 L/minute/ m(2) (n = 32), compared to those with a peak CI of > 4.5 L/minute/m(2) (n = 99), had higher incidences of diabetes mellitus (DM) and hypertension, but had lower hemoglobin levels, estimated glomerular filtration rates (eGFR), oxygen uptake efficiency slope (OUES), and peak oxygen uptake (VO(2)). During the 1.2 ± 0.7 years of follow-up, there were 8 (6.1%) deaths, and 16 (12.2%) HF-related rehospitalizations. In a Cox univariable analysis, a lower event-free survival was associated with a history of DM, a higher Ve/VCO(2) slope, lower peak VCO(2) and eGFR, and a peak CI of ≤ 4.5 L/minute/ m(2) (P < 0.05). The Cox multivariable analysis showed that the Ve/VCO(2) slope (hazard ratio (HR) = 1.08, 95% confidence interval (CI): 1.01~1.16, P = 0.02) and peak CI of ≤ 4.5 L/minute/m(2 )(HR = 3.26, 95% CI: 1.18~9.01, P = 0.02) were significant independent predictors. In conclusion, NICOM during the CPET was demonstrated to provide prognostic information in addition to traditional risk factors, biomarkers, and other well-established CPET parameters.

U-Shape Relationship between Plasma Leucine Level and Mortality in the Intensive Care Unit.

Patients in the intensive care unit (ICU) are at high risk of mortality which is not well predicted. Previous studies noted that leucine has prognostic value in a variety of diseases. This study investigated whether leucine concentration was a useful biomarker of metabolic and nutritional status and 6-month mortality in ICU. We recruited 454 subjects admitted to ICU (348 and 106 in the initiation and validation cohorts, respectively) with an acute physiology and chronic health evaluation (APACHE II) score ≥ 15. We measured plasma leucine concentrations, traditional biomarkers, and calculated APACHE II and sequential organ failure assessment (SOFA) scores. Leucine levels were weakly correlated with albumin, prealbumin, and transferrin levels (r = 0.30, 0.12, and 0.15, p = 0.001, 0.029, and 0.007, respectively). During follow-up, 116 (33.3%) patients died. Compared to patients with leucine levels between 109 and 174 µM, patients with leucine > 174 µM or <109 µM had a lower cumulative survival rate. Death was also associated with age, higher APACHE II and SOFA scores, C-reactive protein, and longer stays in the ICU, but with lower albumin, prealbumin, and transferrin. Patients with leucine levels > 174 µM had higher alanine aminotransferase levels, but no significant differences in other variables; patients with leucine levels < 109 µM had higher APACHE II and SOFA scores, higher incidence of using inotropic agents, longer ICU and hospital stays, but lower albumin and transferrin levels. Multivariable analysis demonstrated that leucine > 174 µM was an independent predictor of mortality, especially early mortality. However, among patients who stayed in ICU longer than two weeks, leucine < 109 µM was an independent predictor of mortality. In addition, leucine < 109 µM was associated with worse ventilator weaning profiles. These findings were similar in the validation cohort. Our study demonstrated a U-shape relationship between leucine levels and mortality rate in ICU.

Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.

AIMS: Previous studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines. METHODS AND RESULTS: This study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax ) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ≥50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 µM. Phenylalanine ≥ 112 µM was associated with a higher mortality rate than was phenylalanine < 112 µM (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ≥ 112 µM was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ≥ 112 µM predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10. CONCLUSIONS: Elevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity.

Tension pneumothorax-induced Takotsubo syndrome: A case report.

RATIONALE: Takotsubo syndrome (TTS) is a form of acute and usually reversible heart failure syndrome. Transient left ventricular dysfunction and electrocardiographic changes could mimic acute coronary syndrome but there are actually no obstructive coronary lesions. PATIENT CONCERNS: A 76-year-old woman with chronic lung disease developed spontaneous tension pneumothorax with the presentation of severe dyspnea, respiratory failure, left ventricular dysfunction, and anterior wall ST-segment elevation on 12-lead electrocardiogram. Acute coronary syndrome was excluded by normal coronary angiograms. DIAGNOSIS: The patient was diagnosed as tension pneumothorax complicated by TTS. INTERVENTIONS: The woman underwent tubal thoracostomy for tension pneumothorax-induced obstructive shock. However, the patient further underwent ligation bullectomy for persistent air leakage 2 weeks later. OUTCOMES: The left ventricular dysfunction recovered 1 week after resolution of tension pneumothorax. Anterior wall ST-segment elevation resolved 25 days after admission. LESSONS: Concurrent electrocardiograms and echocardiographic serial evaluations should be performed to provide more comprehensive information when dealing with tension pneumothorax patients.

Phenylalanine- and leucine-defined metabolic types identify high mortality risk in patients with severe infection.

OBJECTIVE: To investigate the prognostic value of phenylalanine and leucine in patients with severe infection. METHODS: Ninety-three patients with infection who had a quick Sequential Organ Failure Assessment (qSOFA) score ≥2 were enrolled. Plasma phenylalanine, leucine, albumin, C-reactive protein, pre-albumin, and transferrin were measured and the SOFA score at enrollment was calculated after hospitalization. RESULTS: During the 3-month follow-up, 30 (32.3%) patients died. Death was associated with higher SOFA scores, a higher incidence of bacteremia and admission to the intensive care unit, higher C-reactive protein and phenylalanine levels, worse kidney function, and lower pre-albumin and transferrin levels. Patients were categorized into three groups: high-risk type 1 (phenylalanine ≥84µM), high-risk type 2 (phenylalanine <84µM and leucine <93µM), and low-risk (other). Compared to the low-risk type patients, high-risk type 1 and 2 patients had higher mortality rates (hazard ratio 10.1 (95% CI 2.33-43.5) and hazard ratio 5.56 (95% CI 1.22-25.4), respectively). Type 1 patients had higher SOFA scores, a higher incidence of admission to the intensive care unit, and higher C-reactive protein and leucine levels. Type 2 patients had lower albumin and hemoglobin levels. Multivariable analysis showed that both high-risk types were independent predictors of death. CONCLUSIONS: Phenylalanine- and leucine-defined risk classifications provide metabolic information with prognostic value for patients with severe infection.

Layer-specific quantification of myocardial deformation in sepsis-induced Takotsubo cardiomyopathy: Three case reports of a serial 2-dimensional speckle-tracking echocardiographic study.

INTRODUCTION: Little is known about the time-course changes in left ventricular myocardial deformation in patients with Takotsubo cardiomyopathy (TC) using layer-specific quantification of myocardial deformation assessed by 2-dimensional speckle tracking echocardiography (2DSTE). CASE SUMMARY: In this retrospective 2DSTE follow-up study of 3 female patients with sepsis-induced TC, we examined changes in strain among the 3 myocardial layers, and examined the changes in left ventricular diastolic function and right ventricular systolic function. In all 3 patients, there was improvement of at least 15% in left ventricular ejection fractions, and improvement in left ventricular longitudinal and circumferential strains. The absolute differences in left ventricular global strains between the endocardium and epicardium, and between the first and the third 2DSTE studies reflect the following: a decrease in all 3 myocardial layers in patients with acute TC; and a slower improvement in mid-myocardial and epicardial function during recovery of TC. In addition, the right ventricular free wall strains were also impaired in the acute stage of TC with gradual improvement during recovery. CONCLUSIONS: Left ventricular strains did not fully recover even 1 month after acute TC. In addition, right ventricular free wall strains were also impaired in all 3 patients initially. In this case series, we found that layer-specific 2DSTE is a more sensitive method for myocardial function assessment than standard echocardiography.

Plasma P-selectin predicts long-term cardiovascular events in hospitalized patients with suspected coronary artery disease and preserved left ventricular function: a 10-year follow-up study.

BACKGROUND: A variety of biomarkers have been investigated on their values to predict cardiovascular outcomes, such as high-sensitivity C-reactive protein (hs-CRP), fibrinogen, troponin-I (TnI), and soluble P-selectin (sP-sel). By a design of head-to-head comparison, this study sought to figure out the long-term prognostic values of these parameters in patients hospitalized with suspected coronary artery disease. METHODS: A total of 170 patients hospitalized with suspected coronary artery disease were enrolled and followed up for an average of 10 years. sP-sel, hs-CRP, TnI, and fibrinogen levels were measured. During the follow-up period, cardiac events were recorded including cardiac death, non-fatal myocardial infarction, and acute coronary syndromes with hospitalization. RESULTS: For all 170 patients, with a median follow-up time of 9.86 ± 3.87 years, no parameter was able to significantly predict the occurrence of cardiac events. In subgroup analysis, an sP-sel of ≥ 63.5 ng/ml significantly predicted the development of all composite cardiac events only in patients with a left ventricular ejection fraction > 50% (n = 94, p = 0.04). However, the levels of hs-CRP, TnI, and fibrinogen did not have significant predictive values. Multivariate analysis also demonstrated the independent predictive value of sP-sel on all cardiac events (hazard ratio = 5.82, p = 0.02). All parameters, including sP-sel, could not demonstrate prognostic values in patients with a left ventricular ejection fraction ≤ 50% (n = 76). CONCLUSIONS: In this 10-year long-term follow-up study, sP-sel was demonstrated to have prognostic values in predicting the cardiac events in patients with preserved left ventricular systolic function.