Higher Risk Of Death Research Articles

Comparison of the Effectiveness of Body Surface Area Estimation Formulas in Predicting the Risk of Death in Patients with Heart Failure.

Background/Objectives: Body surface area is one of the most important anthropometric parameters in medicine. The study's primary objective is to compare the consistency of the BSA estimation results through applying available formulas. Other objectives include determining the ability of these formulas to discriminate between death and survival in patients, comparing the formulas' diagnostic features, and investigating whether the risk associated with a low BSA is independent of BMI. Methods: This study included 1029 patients (median age, 54 years; female, 13.7%; NYHA I/II/III/IV, 6.3%/36.5%/47.7%/9.5%) diagnosed with heart failure. For each patient, BSA was calculated using 25 formulas. Over the 3-year observation period, 31.2% of the patients died. Results: The average BSA value of the optimal discrimination thresholds was 1.79 m2 ± 0.084 m2 and the BSA difference between the estimators with the lowest (BSAMeeh1879) and the highest (BSANwoye1989) optimal discrimination thresholds was 0.42 m2. The lowest mortality rate was 35.2% and occurred in the subgroup of individuals with BSA values below the optimal discrimination threshold using the BSASchlich2010 estimator. The highest mortality was predicted when the estimator BSAMeeh1879 or BSALivingston&Lee2001 was used. Conclusions: Our study showed a relatively good concordance of 25 BSA estimators in BSA assessment in patients, without extremes of weight or height being known to disrupt it. All BSA estimators presented a significant, although weak, ability to discriminate death from survival at 3-year follow-up; however, BSA is not a very good predictor of HF mortality at 3 years. The higher risk of death in smaller patients, as shown by BSA, was independent of BMI in all but two BSA estimators.

Influence of metastatic sites and burden on oncological outcomes in patients progressing to metastatic castration resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients.MethodsWe relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models.ResultsOf 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05).ConclusionM1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes.

Effects of physical activity on blood pressure and mortality among aged hypertensive patients: A cross-sectional study.

Previous research on physical activity (PA) has mostly concentrated on a single or small number of activities, with scant coverage of the effects of PA on hypertension (HTN) and all-cause mortality. Most studies examining HTN in the elderly have been too small or shown contradictory findings. We conducted a cross-sectional study using 10 cycles of the National Health and Nutrition Examination Survey data from 1999 to 2018. Our sample consisted of respondents aged 65 years or older with HTN, who underwent thorough in-person home interviews. We used a questionnaire to assess their PA levels and divided them into 2 groups: physically active and inactive. We then used logistic analysis to determine the association between PA and death in HTN patients. The gender distribution was nearly equal among the 11,258 participants, with a mean age of 74.36 ± 5.88 years. Nearly 80% of the survey respondents identified as non-Hispanic White. Patients in the physically active group were less likely to suffer from co-morbidities than those in the inactive group. A negative correlation was found between physically active and systolic blood pressure (P < .0001) and a positive correlation between physically active and diastolic blood pressure (P = .0007). There was a much higher risk of death from any cause and heart disease in the inactive group in the uncorrected COX model (HR 2.96, CI 2.65-3.32, P < .0001; HR 3.48, CI 2.64-4.58, P < .0001). The risk of death from any cause and HTN mortality was still significantly higher in the physically inactive group, even after controlling for age, sex, and race or taking all covariates into account. These results have the potential to significantly impact healthcare practices, particularly in the field of geriatric care, by emphasizing the importance of PA in reducing the risk of HTN and mortality in aged patients. The present study underscores the significant benefits of PA in patients aged 65 years and older with HTN. Notably, it was found to reduce systolic blood pressure and have a positive impact on the decrease of all-cause and hypertensive mortality. These findings highlight the crucial role of PA in the health and longevity of aged patients with HTN.

Chemopreventive potential of goniothalamin in diethylnitrosamine-induced hepatocellular carcinoma through the suppression of P13K/AKT signalling pathway.

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.

SACROCOCCYGEALTERATOMA

INTRODUCTION Sacrococcygeal teratomas are the most common of all the GCTs in pediatric age group that originate from the totipotent cells from Hansen\\\'s node or primitive germ cells.(1) incidence is approximately 1 in 40,000 live births with a male to female ratio of 1:3–1:4.Huge and highly vascular SCTs,may result in massive hemorrhagic complications. CASE REPORT A 5 day old male baby delivered via LSCS at 36 WOG was admitted to NICU due to large sacrococcygeal teratoma (20X15cms). The neonate had no other congenital abnormality. Total weight of neonate was 2.7kgs of which tumor was approximately 700gm. Ct Abdomen and pelvis Revealed Type 2 Mature sacrococcygeal teratoma with intrapelvic and large extrapelvic component with Spina bifida occulta and surgical removal of tumour was performed DISCUSSION: Sacrococcygeal tumors can be diagnosed antinatally,the cases with antenatal diagnosis are at a high risk of perinatal complications and fetal death from high output cardiac failure. Early surgical Management in above case and Good postoperative care, minimal blood loss during procedure resulted in Good outcome (2) CONCLUSION Mature sacrococcygeal teratoma appear to be benign in nature and complete surgical resection is main stay of treatment REFERENCES 1)Yadav DK, Acharya SK, Bagga D, Jain V, Dhua A, Goel P. Sacrococcygeal Teratoma: Clinical Characteristics, Management, and Long-term Outcomes in a Prospective Study from a Tertiary Care Center. J Indian Assoc Pediatr Surg. 2020 Jan-Feb;25(1):15-21. 2) Shrestha HK, Shrestha RG. Sacrococcygeal Teratoma: A Case Report. JNMA J Nepal Med Assoc. 2020 Jul 31;58(227):508-511

Identification of m5C-Related gene diagnostic biomarkers for sepsis: a machine learning study.

Sepsis is a serious condition that occurs when the body's response to infection becomes uncontrolled, resulting in a high risk of death. Despite improvements in healthcare, identifying sepsis early is difficult because of its diverse nature and the absence of distinct biomarkers. Recent studies suggest that 5-methylcytosine (m5C)-related genes play a significant role in immune responses, yet their diagnostic potential in sepsis remains unexplored. This research combined and examined four sepsis-related datasets (GSE95233, GSE57065, GSE100159, and GSE65682) sourced from the Gene Expression Omnibus (GEO)database to discover m5C-related genes with differential expression. Various machine learning methods, such as decision tree, random forest, and XGBoost, were utilized in identifying crucial hub genes. Receiver Operating Characteristic (ROC) curve analysis was used to assess the diagnostic accuracy of these genetic markers. Additionally, single-gene enrichment and immune infiltration analyses were conducted to investigate the underlying mechanisms involving these hub genes in sepsis. Three hub genes, DNA Methyltransferase 1 (DNMT1), tumor protein P53 (TP53), and toll-like receptor 8 (TLR8), were identified and validated for their diagnostic efficacy, showing area under the curve (AUC) values above 0.7 in both test and validation sets. Enrichment analyses revealed that these genes are involved in key pathways such as p53 signaling and Toll-like receptor signaling. Immune infiltration analysis indicated significant correlations between hub genes and various immune cell types, suggesting their roles in modulating immune responses during sepsis. The study highlights the diagnostic potential of m5C-related genes in sepsis and their involvement in immune regulation. These findings offer new insights into sepsis pathogenesis and suggest that DNMT1, TP53, and TLR8 could serve as valuable biomarkers for early diagnosis. Further studies should prioritize validating these biomarkers in clinical settings and investigating their potential for therapy.

Acquired long QT interval syndrome as a predictor of sudden cardiac death: Causes, diagnostic criteria, and management strategy

Despite medical advances in diagnosis and treatment, cardiovascular disease remains the leading cause of death worldwide. Sudden cardiac death, an extreme and irreversible outcome of cardiac arrest, is observed in 50% of cases and is often the first suddenly detected pathology. Long QT syndrome is a variant of electrical heart disease resulting from both congenital and acquired dysfunction and/or regulation of cardiomyocyte ion channels, accompanied by impaired depolarization and repolarization of the ventricular myocardium and characterized by QT prolongation and T abnormalities on the electrocardiogram, clinically accompanied by syncope, bidirectional spindle ventricular tachycardia of the “pirouette” type (torsade de pointes), associated with a high risk of sudden cardiac death or sudden arrhythmic death syndrome. Effective management of these patients requires an individualized approach: careful examination, calculation of corrected QT, determination of typology (hereditary or acquired syndrome), risk assessment using the Tisdale scale, and selection of optimal therapy. Treatment should be comprehensive and include pharmacological (beta-adrenergic blockers, correction of electrolyte balance) and surgical (implantable cardioverter-defibrillator and left-sided thoracic sympathetic denervation of the heart), lifestyle (avoidance of drugs that contribute to prolongation of the QT interval, avoidance of specific arrhythmia triggers (active swimming, exposure to loud noises)) and regular consultation with a cardiologist. Early diagnosis and a comprehensive approach are key to successful prevention of sudden cardiac death in patients with Long QT syndrome.

Delirium and Weakness Acquired in the Intensive Care Unit: Individual and Combined Effects on 90-Day Mortality in Survivors of Critical Illness.

To compare the individual and combined effects on 90-day mortality among four critically ill survivor groups: normal (without ICU-acquired delirium or ICU-acquired weakness), delirium-only (with ICU-acquired delirium only), weakness-only (with ICU-acquired weakness only) and delirium-weakness (combined ICU-acquired delirium and weakness). A prospective cohort study consecutively recruited delirium-free critically ill patients admitted to six medical ICUs at a university hospital. Delirium was assessed once daily for 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the ICU. Participants who were discharged from the ICUs were assessed for weakness using the Medical Research Council scale. A summed score below 48 defines ICU-acquired weakness. These survivors were evaluated again for 90-day mortality. The study is reported using the STROBE checklist. Delirium developed in 107 (43.2%) participants during their first 14 days of ICU stay; 55 (22.2%) met criteria for weakness by ICU discharge. Participants with delirium were at increased risk for also developing ICU-acquired weakness, and the 90-day mortality was 18.2%. Independent of age and Acute Physiology and Chronic Health Evaluation II score at ICU admission, delirium-only and weakness-only were not associated with higher 90-day mortality, while participants in the delirium-weakness group had a 3.69-fold higher risk of death, compared to those who were normal during the ICU stay. A non-significant interaction was found, suggesting the joint effect of delirium and weakness on mortality is not higher than the sum of both effects individually. Mortality is substantially high among critically ill survivors who experience both delirium and weakness, although no additive effect on mortality was observed when these conditions occur together. Our findings highlight the urgent need to optimise ICU care by prioritising the prevention, early identification and management of these two common ICU-acquired conditions. Study participation and completion of all assessments. ClinicalTrials.gov identifier: NCT04206306.

Material and social deprivation associated with public health actual causes of death among older people in Europe: longitudinal and multilevel results from the Survey of Health, Ageing and Retirement in Europe (SHARE).

Adverse socioeconomic conditions at the individual and regional levels are associated with an increased risk of mortality. However, few studies have examined this relationship using multilevel analysis and, if so, only within a single country. This study aimed to examine this relationship using data from several European countries. Individual-level data were obtained from Waves 5 to 9 of the Survey of Health, Ageing and Retirement in Europe, while regional-level data were obtained from the Luxembourg Income Study Database. Cox regression analysis with gamma-shared frailty and a random intercept for country of residence was used to examine the association between individual mortality from all causes, cancer, heart attack, and stroke and measures of socioeconomic deprivation at the individual level, including material and social deprivation indices, and at the area level, including the Gini index. The risk of mortality from all causes was increased for respondents with material deprivation (hazard ratio (HR) = 1.77, 95% CI = [1.60, 1.96]) and social deprivation (HR = 7.63, 95% CI = [6.42, 9.07]) compared with those without. A similar association was observed between individual deprivation and the risk of mortality from cancer, heart attack, or stroke. Regional deprivation had a modest contextual effect on the individual risk of death from all causes and cancer. However, when individual-level deprivation was included in the models, no contextual effects were found. The results indicate that individual socioeconomic conditions significantly predict causes of death in older European adults, with those with material deprivation and social deprivation having a higher risk of death from all causes, including cancer, heart attack, and stroke, while the Gini index has a minimal effect, although the Gini index reflects regional disparities across Europe.

Novel FLNC variants in pediatric cardiomyopathy: an insight into disease mechanisms

BackgroundFLNC gene variants have predominantly been reported in adult populations with cardiomyopathies, and early-onset cases are less common. The genotype–phenotype relationship indicates that dilated cardiomyopathy (DCM) is often associated with FLNC truncating variants.MethodsWe conducted a comprehensive genetic analysis using next generation sequencing (NGS) to identify FLNC variants in patients with cardiovascular conditions. Detailed phenotypic and variant analyses were performed to characterize the clinical features and genetic alterations. Minigene assays and structural modeling were used to investigate the pathogenicity caused by the identified variants.ResultsIn a cohort of 58 patients, novel heterozygous FLNC variants, c.3962A > T (p.Glu1321Val) and c.7543C > T (p.Leu2515Phe), were identified in patients presenting with dilated and mixed restrictive/hypertrophic cardiomyopathies, respectively. The c.3962A > T variant disrupted normal splicing, as demonstrated through the splicing prediction tool and minigene studies, further emphasizing its pathogenic potential.ConclusionFor missense variants of FLNC in patients with DCM, the splicing effect of the variant should be carefully checked. Early detection and intervention are crucial given the high risk of sudden cardiac death and severe cardiac complications.

Risk of death after type of intimate partner violence (IPV) involvement

Abstract Background Most studies have focused on women’s intimate partner violence (IPV) victimization but perpetration and bi-directional violence remain understudied. Methods Using linked criminal justice and population registers in Manitoba, Canada, we assessed the risk of death according to the role in IPV incidents (accused-only, victim-only, bidirectional, none). In this retrospective matched cohort study, we assembled a cohort of 212,068 adults who were followed from April 2004 to March 2023 to assess IPV incidents and subsequent death. Those involved in an IPV incident were 1:3 matched to persons with no history of IPV based on birth year, sex and marital status at the time of the incident. Results Men comprised 85% of accused-only, 21% of victim-only, and 50-51% in the other two groups. Overall, compared to those without IPV involvement, the adjusted Hazard Ratios for all-cause mortality were 1.38 [95% Confidence Intervals (CI): 1.28, 1.49] for accused-only, 1.39 (1.29, 1.50) for victim-only and 1.45 (1.19, 1.77) for bidirectional IPV. The associations were stronger among women, particularly that of bidirectional violence [1.24 (0.97, 1.60) among men and 1.92 (1.39, 2.66) among women]. Similar patterns were found for intentional mortality [0.96 (0.56, 1.64) among men and 2.43 (1.27, 4.65) among women]. Conclusions There are clear sex inequities in IPV involvement. Any type IPV involvement is associated with higher risk of death, particularly among women, who comprise most of the victims. Key messages • Any type IPV involvement is associated with higher risk of death, particularly among women, who comprise most of the victim. • Use of linked criminal justice data allows studying the consequences of IPV victimization, perpetration and bidirectional violence and monitor gender inequities over time.

The triglyceride-glucose index, ventricular arrhythmias and major cardiovascular events in patients at high risk of sudden cardiac death

BackgroundThe association between the triglyceride-glucose (TyG) index and ventricular arrhythmias (VAs) is unclear. This study aimed to investigate the relationship between the TyG index, VAs, and major cardiovascular events in patients at high risk of sudden cardiac death (SCD).MethodsWe enrolled 1046 patients at high risk of SCD with an indication for implantable cardioverter-defibrillator (ICD) implantation at the Chinese National Center for Cardiovascular Diseases. The primary outcome was VAs, defined as sustained ventricular tachycardia and ventricular fibrillation documented by the ICD. The secondary outcomes were cardiac mortality, heart transplantation, and rehospitalization for heart failure.ResultsThe mean (± SD) age was 59.6 ± 14.0 years old, and 25.7% were female. During the mean follow-up of 36.1 months, 342 (32.7%) patients had VAs, and 185 (17.7%) patients had major cardiovascular events. The mean fasting glucose and triglyceride levels were 111.9 ± 42.7 mg/dL and 140.0 ± 95.4 mg/L, respectively, with a TyG index range of 6.96–11.8. In the Fine-Gray subdistribution hazard model analysis, an increase in the TyG index was associated with a significant increase in the VAs (per 1 TyG index, hazard ratio [HR] 2.95; 95% confidence interval [CI], 2.29–3.80) and secondary outcome (HR 2.84; 95% CI 1.86–4.34). When stratified into tertiles, the risk of VAs was significantly higher in the highest tertile (HR 4.08; 95% CI, 2.81–5.92) than in the lowest tertile. Analysis of the secondary outcome revealed similar findings (HR 3.18; 95% CI, 1.73–5.85).ConclusionsIn our cohort, the pre-operational TyG index is significantly associated with VAs and major cardiovascular events for patients with high risk of SCD.

National early warning score predicts 90 days all-cause mortality among patients with acute heart failure

Abstract Background Acute heart failure (AHF) is defined as new-onset or worsening of symptoms and signs of heart failure including symptoms or signs related to congestion and volume overload. Patients presenting with AHF are a heterogeneous group as AHF is not a specific disease but a shared clinical presentation of different cardiac abnormalities. Due to the heterogeneity of the patient population, a prognostic tool is needed to identify AHF patients with a high risk of death. The National Early Warning Score (NEWS) is a system for scoring the vital signs that are measured at the patient's bedside and is developed to predict acute mortality within 24 hours. The NEWS has previously been used to evaluate all cost mortality for patients admitted to the Emergency Department (ED). There is limited data regarding the role of the NEWS in predicting adverse outcomes in patients with acute heart failure. Purpose To evaluate NEWS measured at the ED and clinical outcomes in patients with AHF. Methods This prospective, observational cohort study included consecutive patients with AHF admitted through the emergency department (ED) at a large public hospital from 10 March 2020 to 31 March 2022 and had a follow-up period of 365 days. Trained cardiologists assessed all patients for the presence of AHF. According to the cut-off value for the NEWS, high-risk groups are defined by a NEWS score &amp;gt; 7. The patients were categorized into two groups, high-risk and low-risk, depending on the scores they received from the NEWS assessment. The primary outcome was all-cause mortality at 90 days. We used multivariable Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, smoking, known heart failure (HF), and lactate levels at admission. Results In the study period from March 10, 2020, to March 31, 2022, 408 patients were identified with AHF. Upon arrival to the ED, the median first NEWS was 4 (IQR 2-6). 323 patients were categorized in the low-risk group and 69 patients in the high-risk group. 16 patients had missing values upon arrival at the ED. The high-risk group exhibited significantly faster heart rate, lower saturation, and higher oxygen demand compared. A Kaplan-Meier plot revealed a statistically significant difference in all-cause mortality over 90 days between low-risk and high-risk groups among AHF patients (log rank, p-value &amp;lt; 0.001). After multivariable adjustment, NEWS&amp;gt;7 (HR, 1.69; CI, 1.18 to 2.45) (p-value= 0.004) and higher age (HR, 1.04; CI 1.03 to 1.07) were statistically associated with higher all-cause mortality (p &amp;lt;0.001). Conclusion In this prospective, observational cohort study of AHF patients presenting at the ED an initial NEWS &amp;gt;7 was associated with a significant all-cause mortality after 90 days.GRAPHIC ABSTRACT

Therapeutic hypothermia after out-of-hospital cardiac arrest in comatose patients with acute myocardial infarction

Abstract Background Comatous survivors of out-of-hospital cardiac arrest (OHCA) have a high risk of death or poor neurological outcome. Therapeutic hypothermia is recommended for these patients after OHCA. However, there is a lack of data regarding outcomes of therapeutic hypothermia after OHCA in comatose patients with acute myocardial infarction (AMI). Purpose This study aimed to investigate the impact of therapeutic hypothermia on clinical outcomes in comatose patients who underwent primary percutaneous coronary intervention (PCI) for AMI after OHCA. Methods Using a prospective nationwide registry from 2016 to 2021, we examined 2,925 consecutive comatose patients experiencing OHCA in patients with AMI. These patients were categorized into groups receiving hypothermia treatment (n=624) and those without hypothermia treatment (n=2,301). The primary endpoint was the mortality rate upon discharge. The secondary endpoints were mortality rates at 6 or 24 hours, and neurological outcomes at hospital discharge. Results Overall, 624 (21.3%) patients were classified into the hypothermia group. This group showed a notably reduced mortality rate (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.58-0.78, p&amp;lt;0.001) after IPTW analysis (Figure 1). While the worse neurological outcome (as indicated by cerebral performance category [CPC] category 3-5) at hospital discharge was not significantly different between groups after IPTW analysis (odds ratio [OR]: 1.04, 95% CI: 0.93-1.15, p=0.499), early hypothermia within 180 minutes after hospital arrival showed significantly lower mortality rates (HR: 0.64, 95% CI: 0.44-0.95, p=0.027) and reduced occurrence of worse neurological outcome (OR: 0.75, 95% CI: 0.59-0.96, p=0.021) after IPTW analysis (Figure 2). Detailed hypothermia protocol including a targeted temperature of 33°C vs. 36°C or hypothermia duration of 48 hours vs. 24 hours did not significantly reduce the rate of death or poor neurological outcome at discharge. Conclusions Therapeutic hypothermia in OHCA patients complicating AMI was associated with lower mortality rates and comparable neurologic outcomes. However, early hypothermia within 180 minutes after hospital arrival showed significantly improved the mortality and neurological outcomes.all-cause deathAll-cause death and neurological outcome

Risk of death in patients with early cardiovascular complications following ischaemic stroke: an individual patient data pooled analysis from the VISTA database

Abstract Background Early cardiovascular complications may occur in patients following ischaemic stroke (stroke-heart-syndrome, SHS). We investigated the risk of death in patients with SHS, and across the SHS manifestations. Methods Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]), i.e. those with SHS and those with stroke-only (without SHS). Using Cox proportional hazards model, we evaluated the 90-day risk of death trajectories associated with SHS. We also compared the 90-day risk of death across SHS manifestations excluding CRA, using multivariate analysis. Results Among 15,054 patients with ischaemic stroke (mean age 72±11 years; 55% male), 1,787 (11.8%; 95% confidence interval [CI]: 11.3-12.3, Table 1) developed SHS, with incidence peaked at day 3 post-stroke (interquartile range: 2-5). Other arrhythmia/ECG abnormalities were the most prevalent (6.5%; 95%CI: 6.1-6.9), followed by AF/AFL, HF/LV dysfunction, ACS/acute myocardial injury, and CRA. Patients who developed SHS between 10-30 days post-stroke had significantly higher risks of death compared to those with SHS within the first 0-3 days (adjusted hazard ratio [HR]: 2.13 [1.57-2.89]). In the multivariate-adjusted analysis which includes 13 background factors such as age and sex, SHS manifested as ACS/acute myocardial injury and HF/LV dysfunction were associated with highest risk of death within 90-day post-stroke (adjusted hazard ratio [HR] [95% CI], HR 2.13 (1.08-4.18) and HR 2.28 (1.42-3.66), respectively, Figure 1). Conclusions Stroke-heart syndrome is associated with high risk of death, with greater risk observed with the delayed SHS onset. Among the SHS manifestations, ACS/acute myocardial injury and HF/LV dysfunction were associated with the highest risk of death post-stroke.Figure 1

Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF

Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH

Demographics and clinical outcomes of flow-gradient patterns of aortic stenosis: an analysis of the CURRENT AS Registry-2

Abstract Background Low-gradient (LG) severe aortic stenosis (AS) has not been fully characterized compared with high-gradient (HG) AS. Methods Among 3369 patients with severe AS enrolled in the CURRENT AS Registry-2, the current study population consisted of 3363 patients with data on left ventricular ejection fraction (LVEF) after excluding patients with LG AS without indexed stroke volume data. Patients were divided into 4 groups (LG AS with reduced LVEF: N=285, paradoxical low-flow low-gradient [LFLG] AS: N=220, normal-flow low-gradient [NFLG] AS: N=872, and HG AS: N=1986). Results Compared to HG AS, LG AS with reduced LVEF more often had cardiovascular comorbidities, advanced cardiac damage stages, and frailty with less extensive aortic valve (AV) calcification by computed tomography (CT), and paradoxical LFLG AS more often had atrial fibrillation, concomitant valvular disease, advanced cardiac damage stages, and frailty with less extensive AV calcification, while NFLG AS were less often symptomatic, and had comparable cardiac damage stages, and frailty with less extensive AV calcification. Patients with the 3 types of LG AS less often underwent surgical or transcatheter aortic valve replacement than those with HG AS (cumulative 3-year incidence: LG AS with reduced LVEF: 64.5%, paradoxical LFLG AS: 59.1%, NFLG AS: 54.2%, and HG AS: 87.3%, P&amp;lt;0.001). Cumulative 3-year incidence of death or heart failure hospitalization was much higher in patients with LG AS with reduced LVEF and paradoxical LFLG AS than in those with HG AS (cumulative 3-year incidence: LG AS with reduced LVEF: 65.9%, paradoxical LFLG: 51.1%, NFLG: 35.5%, and HG: 30.5%, P&amp;lt;0.001). After adjusting confounders, LG AS with reduced LVEF and paradoxical LFLG AS compared with HG AS were independently associated with higher risk for death or heart failure hospitalization (HR: 1.82, 95%CI: 1.49-2.23, P&amp;lt;0.001; HR 1.43, 95%CI: 1.13-1.82, P=0.003, respectively), but not NFLG AS (HR 1.03, 95%CI: 0.88-1.21, P=0.68). Conclusions Aortic stenosis might be less severe in LG AS than in HG AS when assessed by the CT calcium score of the aortic valve, and each of the 3 hemodynamic types of LG AS had distinct clinical, and echocardiographic characteristics as well as clinical outcomes that were different from HG AS.Different patterns of severe AS

Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome

Abstract Background Treatment with eicosapentaenoic acid (EA) has been shown to reduce the incidence of cardiovascular adverse events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (&amp;gt;135 mg/dl) and non-elevated (&amp;lt;100 mg/dl) low-density lipoprotein cholesterol (LDLc). Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. Patients with LDLc &amp;lt;100 mg/dl and triglycerides &amp;gt;135 mg/dl were analyzed as candidates to EA. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women and 30.4% with an ST-elevation ACS. Mean LDLc was 99.8 (38.5) mg/dl and median triglycerides 120.5 (interquartile range 90-197) mg/dl. A total of 3,028 (20.9%) were classified as candidates for EA, and they had the same mean age (p=0.87) but significantly higher prevalence of diabetes (35.1% vs. 21.9%), dyslipidemia (63.5% vs. 50.1%), previous coronary heart disease (CHD) (25.9% vs. 13.9%), or heart failure (HF) (3.6% vs. 2.5%). Candidates less frequently had an ST-elevation ACS (26.6% vs. 34.1%; p=0.02) and the incidence of Killip &amp;gt;1 was equivalent in candidates vs. non-candidates (16.6% vs. 17.7%; p=0.15). Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE. Candidates for EA had higher mortality (18.4% vs. 14.0%; HR: 1.22 95% CI 1.11-1.35) and MACE (39.0% vs. 33.6%; HR 1.14 95% CI 1.06-1.21) rates. Multivariate analysis (figure), adjusted for age, sex, diabetes (DM), previous coronary heart disease (CHD) or heart failure (HF), and medical treatments at discharge, identified an independently higher risk for all-cause mortality among candidates for EA (HR: 1.15 95% CI 1.04-1.26) [Figure 1] and for MACE (HR: 1.14 95% CI 1.05-1.20). The risk was consistent in all subgroups except for the case of mortality, but not for MACE, and previous ACS (figure 2) were a significant interaction (p=0.01) was observed Conclusions Approximately 20% of patients discharged after an ACS could be candidates for EA, and this subset of patients are at higher risk of death or a first MACE.

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

Effect of triglycerides on cardiovascular risk in patients with a first vs. recurrent acute coronary syndrome

Abstract Background Triglyceride (TG) levels have gained increasing interest in the prevention of cardiovascular disease although there is divergent evidence that might be explained by confounding factors. Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. TG were measured during the hospitalization, and mortality and major adverse cardiovascular events (MACE) were analyzed through follow-up. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women, and 30.4% with an ST-elevation ACS; 2,378 (16.4%) patients had a previous ACS and were classified as recurrent ACS. Median triglyceride level was 120.5 (interquartile range [IQRS] 90-197) mg/dL and was slightly higher in patients with recurrent ACS (135 IQR 98-186 vs. 129 IQR 95-175; p&amp;lt;0.01). Patients with first vs. recurrent ACS received ticagrelor or prasugrel more frequently at discharge (14.8% vs. 7.4%; p&amp;lt;0.01), but no other differences in medical treatments were observed. Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE during follow-up. Patients with recurrent ACS had higher mortality (32.9% vs. 11.4%; p&amp;lt;0.01) and MACE (46.5% vs. 32.4%; p&amp;lt;0.01) rates. Multivariate analysis, adjusted for age, sex, diabetes, previous heart failure, and medical treatments at discharge showed that TG levels were not associated with higher risk of mortality (p=0.29) but with higher risk of MACE (p=0.04). A significant interaction (p=0.01) was observed for TG and previous ACS for both endpoints and, therefore, analyses were performed separately (Figure 1). As shown in Figure 2, TG were associated with higher risk of death in patients with first ACS (p=0.02) but not in patients with recurrent ACS (p=0.48); in contrast, TG were associated with higher risk of MACE (p=0.024) in patients with a recurrent ACS but not in patients with a first ACS (p=0.25). Conclusions Previous ACS modifies the risk of TG on mortality and MACE in patients discharged after an ACS. TG might be considered a target for treatment in patients after a first or recurrent ACS, although the exact impact on outcomes might be different.