Higher All-cause Mortality Research Articles

Comparison of effective regurgitant orifice area by the PISA method and tricuspid coaptation gap measurement to identify very severe tricuspid regurgitation and stratify mortality risk

Abstract Background Various definitions of very severe (VS) tricuspid regurgitation (TR) have been proposed based on the effective regurgitant orifice area (EROA) or tricuspid coaptation gap (TCG). Because of the inherent limitations associated with the EROA, we hypothesized that the TCG would be more suitable for defining VSTR and predicting outcomes. Purpose To compare EROA and TCG for outcome prediction in patients with severe TR. Methods In this French multicentre retrospective study, we included 606 patients with ≥ moderate-to-severe isolated TR (without structural valve disease or an overt cardiac cause) according to the recommendations of the European Association of Cardiovascular Imaging. Patients were further stratified into VSTR according to the EROA (≥60 mm²) and then according to the TCG (≥10 mm). The primary endpoint was all-cause mortality and the secondary endpoint was cardiovascular mortality. Results The relationship between the EROA and TCG was poor (R²=0.21), especially when the size of the defect was large. Four-year survival was comparable between patients with an EROA <60 mm² vs. ≥ 60 mm² (67±3% vs. 64±4%, p=0.64), even after adjustment, for all-cause (p=0.72) and cardiovascular mortality (p=0.18). A TCG ≥10 mm was associated with lower four-year survival than a TCG <10 mm (53±7% vs. 69±3%, p<0.001). After adjustment for covariates, including age, comorbidity, right heart failure, dose of diuretics, and right ventricular dysfunction, a TCG ≥10 mm remained independently associated with higher all-cause mortality (adjusted HR[95%CI]=1.46[1.15-2.18], p=0.015) and cardiovascular mortality (adjusted HR[95%CI]=1.95[1.22-3.14], p <0.001), whereas an EROA ≥60 mm² was not associated with all-cause or cardiovascular mortality (adjusted HR[95%CI]:1.07[0.75-1.51], p=0.720, and adjusted HR[95%CI]:1.35[0.87-2.09], p=0.176, respectively). Conclusion The correlation between the TCG and EROA is weak and decreases with increasing defect size. A TCG ≥10mm is associated with increased all-cause and cardiovascular mortality and should be used to define VSTR in isolated TR.Correlation between EROA and TCGEvent free survival curves

Clustering of vascular aging manifestations and incident cardiovascular events. The Paris Prospective Study III

Abstract Background Vascular aging is a key contributor to cardiovascular disease (CVD). Manifestations of vascular aging are heterogeneous and include atherosclerosis, arterial stiffening, increased arterial wall stress and arterial diameter enlargement. These manifestations have different pathophysiological mechanisms and likely require different prevention strategies. How the different vascular aging manifestations co-exist, or cluster, at the individual level and the association of any such clusters with incident CVD is unknown. Purpose To examine how vascular aging manifestations cluster and whether any such clusters are associated with incident CVD. Methods In the Paris Prospective Study III, a French community-based prospective study on novel determinants of CVD, 10,157 participants underwent a high-resolution carotid echotracking (Artlab, Esaote) between 2008 and 2012, and were thereafter monitored every two years for CVD events up to end 2020 . Hospitalized stroke and coronary heart disease (CHD) events were validated after the review of all medical records. Hierarchical clustering analysis was employed to identify patterns of vascular aging. Hazard ratios (HRs) were quantified in Cox models. Results The study sample included 8,360 participants (39% women, mean age 59.6 years) without prevalent CVD. Three clusters of vascular aging manifestations were identified: - Cluster 1 included 3,995 (47.8%) participants and was characterized by low prevalence of carotid plaques, low carotid intima-media thickness (IMT), low carotid artery stiffness, small carotid diameter and low carotid circumferential wall stress (healthy vascular aging cluster). - Cluster 2 included 2,109 (25.2%) participants and was characterized by high carotid artery stiffness and high carotid circumferential wall stress (arterial stiffness vascular aging cluster). - Cluster 3 included 2,256 (27.0%) participants, and was characterized by high prevalence of carotid plaques and high carotid IMT(atherosclerosis vascular aging cluster). After a median follow-up of 8.5 years, 108 incident stroke events, 218 CHD events and 192 deaths occurred. Compared with cluster 1, cluster 2 (HR 1.76, [95%CI, 1.06-2.94]), but not cluster 3 (HR 1.57, [0.94-2.62]), was associated with a higher risk of stroke. In addition, compared to cluster 1, cluster 3 (HR 1.53, [1.08-2.16]), but not cluster 2 (HR 1.38, [95% CI, 0.96-1.98]), was associated with higher risk of CHD. Both cluster 2 and 3 were associated with higher all-cause mortality (HR for cluster 2: 1.50, [1.02-2.21]; HR for cluster 3: 1.48, [1.01-2.17]). Internal validation using bootstrapping methods (n=1000 samples) provided consistent findings. Conclusion The simultaneous analysis of carotid-echotracking vascular aging parameters identified three patterns of vascular aging that are differentially associated with CHD and stroke in the community.Carotid properties by clustersKM survival curves by clusters

Inequality and COVID-19 in Sweden: Relative risks of nine bad life events, by four social gradients, in pandemic vs. prepandemic years.

The COVID-19 pandemic struck societies directly and indirectly, not just challenging population health but disrupting many aspects of life. Different effects of the spreading virus-and the measures to fight it-are reported and discussed in different scientific fora, with hard-to-compare methods and metrics from different traditions. While the pandemic struck some groups more than others, it is difficult to assess the comprehensive impact on social inequalities. This paper gauges social inequalities using individual-level administrative data for Sweden's entire population. We describe and analyze the relative risks for different social groups in four dimensions-gender, education, income, and world region of birth-to experience three types of COVID-19 incidence, as well as six additional negative life outcomes that reflect general health, access to medical care, and economic strain. During the pandemic, the overall population faced severe morbidity and mortality from COVID-19 and saw higher all-cause mortality, income losses and unemployment risks, as well as reduced access to medical care. These burdens fell more heavily on individuals with low income or education and on immigrants. Although these vulnerable groups experienced larger absolute risks of suffering the direct and indirect consequences of the pandemic, the relative risks in pandemic years (2020 and 2021) were conspicuously similar to those in prepandemic years (2016 to 2019).

Cardiometabolic comorbidities in autosomal dominant polycystic kidney disease: a 16-year retrospective cohort study

BackgroundAutosomal-dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease and the fourth leading cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Nevertheless, there is a paucity of epidemiological research examining the risk factors and survival on RRT for ADPKD. Thus, we aimed to investigate the cumulative effects of cardiometabolic comorbidities, including hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia (DLP) to clinical outcomes in ADPKD.MethodsWe identified 6,142 patients with ADPKD aged ≥ 20 years from 2000 to 2015 using a nationwide population-based database. HTN, DM, and DLP diagnoses before or at the time of ADPKD diagnosis and different combinations of the three diagnoses were used as the predictors for the outcomes. Survival analyses were used to estimate the adjusted mortality risk from cardiometabolic comorbidities and the risk for renal survival.ResultsPatients with ADPKD who developed ESRD had the higher all-cause mortality (HR, 5.14; [95% CI: 3.88–6.80]). Patients with all three of the diseases had a significantly higher risk of entering ESRD (HR:4.15, [95% CI:3.27–5.27]), followed by those with HTN and DM (HR:3.62, [95% CI:2.82–4.65]), HTN and DLP (HR:3.54, [95% CI:2.91–4.31]), and HTN alone (HR:3.10, [95% CI:2.62–3.66]) compared with those without any three cardiometabolic comorbidities.ConclusionsOur study discovered the cumulative effect of HTN, DM, and DLP on the risk of developing ESRD, which reinforces the urgency of proactive prevention of cardiometabolic comorbidities to improve renal outcomes and overall survival in ADPKD patients.

Tricuspid regurgitation impact on outcomes (TRIO) score: an evaluation tool for patients undergoing tricuspid valve surgery?

Abstract Background Isolated tricuspid regurgitation (TR) repair or replacement carries significant operative mortality risk mainly due to delayed referral. We have recently developed the Tricuspid Regurgitation Impact on Outcomes (TRIO) score to assess risk in TR based on 8 simple variables (age, sex, severe TR, creatinine>2 mg/dl, history of heart failure, history of chronic lung disease, AST >40 units/L, heart rate >90). Whether this score can be used in assessment of TR surgical risk and long term outcome is unknown. Purpose To examine the impact of TRIO scores on the postoperative outcomes of isolated tricuspid valve surgery. Methods Adult patients with severe functional TR who underwent isolated tricuspid valve replacement or repair between 2000-2022 were identified. Postoperative outcomes were compared across low (0-3), intermediate (4-6), and high (7-12) TRIO risk score groups. Results 177 patients were included. Mean age was 70.7 ± 12.2 years, 69 (39%) were male, 34 (19%) were low TRIO score, 111 (63%) intermediate score and 32 (18%) high score. Tricuspid repair was performed in 43 (24.3%) and valve replacement in 134 (75.7%), reflecting the advanced disease stages of this patient cohort. At short term, higher TRIO scores were associated with more frequent need for urgent surgery, prolonged ventilation (>72h) and postoperative dialysis (p<0.05 for all). Perioperative 30-day mortality increased with the TRIO risk score (low: 0%; intermediate: 4.5%; high: 9.4%) but differences did not reach statistical significance (p=0.187). Low risk patients had a shorter hospital and ICU stay (Figure 1A-B). During a mean follow-up of 5.2 ± 3.2 years, 98 (55.4%) patients died. At long term follow-up, lower TRIO scores were associated with improved survival after tricuspid surgery (Figure 1C). Conclusions Patients with higher TRIO scores have more postoperative complications, require longer hospital stay and have higher all-cause mortality at long-term follow-up. Our findings suggest that TRIO score may also be used for risk stratification in patients considered for surgical management of isolated functional TR.

Bleeding risk profile and heart failure hospitalizations in patients with atrial fibrillation according to FIB-4 index

Abstract Introduction Fibrosis-4 index (FIB-4 index), calculated by age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count, is a simple marker to evaluate liver fibrosis. The FIB-4 index is associated with higher all-cause mortality in patients with heart failure (HF). However, the relationship between liver stiffness and atrial fibrillation remains unclear. Purpose The present study explores the impact of the FIB-4 index in the bleeding risk and heart failure hospitalizations among a large cohort of AF patients. Methods The Fibrosis-4 index (FIB-4) was applied to 10,530 patients diagnosed with AF from our health area between January 2014 and April 2020. Patients were analyzed in three regions of the Fib-4index based on the cutoff points (Group 1 F0<1.30, group 2 F1-F2:1.30–2.67 and group 3 F3-F4: >2.67). The outcome was a composite of major bleeding events and hospitalization for heart failure. The risk of the combined end-point was determined by competing risk regression. Results 4471 patients (42.5 %) were included in Group 1, 5139 (48.8 %) in Group 2 and 920 (7.4%) in Group 3. During a mean follow-up of 3.78±2.05 years, 1,834 patients died (17.49%), 2,359 had a heart failure hospitalization (22,42%) and 772 had a major bleeding (7.36%). The incidence of major bleeding and heart failure hospitalizations was significantly higher amongst group 3. In the univariate analysis, group 2 and group 3 were associated with increased risk of the combined outcome (Figure 1). Multivariate adjustment was developed including all those variables with clinical significance and those that had been associated in the univariate analysis. Group 3 was associated with higher increased risk of major bleeding and heart failure hospitalizations (sHR 1.21, 95% CI 1.05-1.39; P=0.007), whilst Group 2 not (1.06, 95% CI 0.97-1.16; P=0.169) in comparison with Group 1. Conclusions FIB4 index >2.67 was associated with higher risk of major bleeding and heart failure hospitalizations. FIB-4 index may reflect venous congestion and it could be an useful tool for predicting HF and major bleeding events in patients with AF.Figure 1

Effect of a restrictive vs. liberal blood transfusion strategy among patients with acute myocardial infarction and anemia according to heart failure. A subgroup analysis of the REALITY trial

Abstract Background/Introduction The optimal Red Blood Cell (RBC) transfusion strategy in patients with acute myocardial infarction (MI) and anemia remains debated. In REALITY, the largest randomized trial to date in this population (n=666), a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days, but did not achieve non-inferiority at 1 year. One of the main concerns with RBC transfusion is the risk of fluid overload and acute heart failure (HF). Therefore, the balance of benefit and risk of transfusions strategies may differ between patients with and without heart failure. Purpose We aimed to evaluate the potential interaction between HF and RBC transfusion on outcomes in REALITY. Methods HF was defined as either a history of heart failure or Killip class > 1 at randomization (data available for 658 patients). All events until day 30, including HF, were adjudicated by a Critical Event Committee blinded to the transfusion arm and hemoglobin levels. The primary clinical outcome was MACE at 30 days. Secondary endpoints included MACE at one year, individual components of MACE and new onset of heart failure at 30 days and 1 year. Results Among 658 patients, 311 (47.3 %) had HF. HF patients had a higher rate of MACE and a higher rate of new HF than patients without HF at 30 day and at 1 year (Fig 1). There was no interaction between HF and the effect of randomized assignment on the primary outcome or on new HF. In contrast, a liberal strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF but not in pts without HF (interaction p = 0.0088 and p = 0.049 respectively, Fig 1). Conclusion(s) Heart failure is frequent in MI patients with anemia (nearly half of the patients) and is associated with higher risks of MACE and of HF. While no interaction was observed between HF and transfusion strategies on the primary outcome of MACE, a liberal transfusion strategy was associated with higher all-cause mortality than a restrictive strategy both at 30-days and 1 year. The mechanism of this interaction deserves further investigation.

The association between obesity and mortality in otherwise metabolically healthy COVID-19 patients with cardiac arrest: insights from a National Inpatient Sample in the US, 2020

Abstract Background Existing studies suggest poor outcomes among SARS-CoV-2 patients who had underlying obesity and metabolic syndrome (MBS). Therefore, we planned to do this study as no study so far has assessed the association of obesity with outcomes in individuals with SARS-CoV-2 infection who are metabolically healthy. Methods We queried the National Inpatient Sample (2019) using the ICD-10 codes for COVID-19 patients who had a cardiac arrest and were metabolically healthy (without Hypertension, Hyperlipidemia and Diabetes). Baseline characteristics, comorbidities, healthcare resource utilization statistics, and all-cause mortality were compared between obese and non-obese cohorts. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results After cleaning the data for missing data total COVID-19 with cardiac arrest-related hospitalizations were 5885 (obese 1410 vs non-obese 4475). Propensity score matching, 1:1 ratio, for age, sex and race led to a final population of 2140 (obese 1070 vs non-obese 1070). In propensity-matched samples, COVID-19 with cardiac arrest with obesity were mainly black (42.1% vs 37.9%; p=0.03), private payer (43.1% vs 24.5%; p<0.001), visiting the urban non-teaching hospital (26.2% vs 16.8%; p<0.001) compared to non-obese. Besides, COVID-19 patients with cardiac arrest were smokers (15.4% vs 13.6%), high burden of peripheral vascular disease, and had prior coronary artery bypass grafts. Before matching, 1510 obese patients with COVID-19 with cardiac arrest, 1300 (86.10%) died vs 4105 (81.7%) of 5025 non-obese with cardiac arrest; p<0.05. Besides, obese patients had significantly high all-cause mortality (83.6% vs 78.0%; p=0.001), transfer to short-term hospital (17.1% vs 11.4%; p=0.001), and high hospital cost (median $434336 vs $338450; p=0.001) compared to non-obese patients in propensity match cohort [Table 1]. Furthermore, in the subgroup analysis, high mortality in obese patients was noted in young Age 18-44 years, 45-64 years, in females, White, black, low household income,0-25, (88.9% vs 77.9%;p<0.001) compared to non-obese patients. However, after adjustment for covariates, the odd for all-cause mortality in patients with obesity was high (OR 1.67; CI 95%, 0.99-2.82), but failed to attain significance [Table 2]. Conclusion The burden of obesity in otherwise metabolically healthy COVID-19 patients admitted with cardiac arrest remained very high (nearly 1 in every 4 patients). COVID-19 patients with cardiac arrest had higher mortality in obese patients, especially those of young age, female and low-income patients. However, when adjusted for covariates the multivariate analysis failed to reach a statistical significance which warrant further large-scale studies to understand the independent association of higher BMI or obesity on survival in this high-risk patient population.

Abstract 17932: Smoking History is Associated With Worse Outcomes in Patients With Sarcopenia Admitted for Acute Decompensated Heart Failure

Background: Sarcopenia and smoking are independently associated with worse heart failure (HF) outcomes; therefore, their combined effect is likely even more detrimental. Research Questions: We studied the impact of sarcopenia and smoking on outcomes in patients admitted for acute decompensated HF (ADHF). Methods: We conducted a retrospective cohort study of 406 consecutive patients hospitalized at our tertiary care center for ADHF from 2017 to 2020 with computed tomography of the chest one month before the discharge date. Semi-automatic measurements were made at T12 (Figure 1A) and adjusted for height squared to obtain skeletal muscle index (SMI). To compare survival, patients were divided into four groups: nonsarcopenic nonsmokers (controls, 22.4%), sarcopenic nonsmokers (10.6%), nonsarcopenic smokers (44.3%), and sarcopenic smokers (22.7%). Sarcopenia was the lowest sex-stratified SMI tertile (cutoffs of 29.6 cm 2 /m 2 in males and 25.7 cm 2 /m 2 in females), and smokers were those who had ever smoked. Results: The mean admission age of our cohort was 70±14 years, 44.3% were female, and 67.0% had a smoking history (191 former and 81 active). Compared to nonsmokers, patients with a smoking history had more COPD (53.3% vs. 18.7%, p<0.001) and higher all-cause mortality (HR 1.41, 95%CI 1.05-1.90, p=0.021), but did not differ in SMI. When further stratified by sarcopenia, during a median 22.9 (3.0-33.5) months of follow-up, all groups had higher all-cause mortality when compared to controls (figure 1B); the highest rate was seen in sarcopenic smokers, which remained significant when adjusted for age, male sex, Caucasian race, CAD, and COPD (HR 1.71, 95%CI 1.12-2.60, p=0.013). Sarcopenic smokers also had the highest rate of ICU admissions (50.0%). Conclusions: Sarcopenia and smoking portend worse prognoses in patients admitted for ADHF, with sarcopenic smokers having the worst outcomes, independent of COPD history.

Abstract 14162: Long-Term Outcomes for Contemporary Mechanical versus Bioprosthetic Surgical Mitral Valve Replacement in Patients Aged 50 to 70 Years

Background: Guidelines are still unclear regarding whether mechanical or bioprosthetic valves should be selected for mitral valve replacement (MVR) in patients aged 50-70 years. Aims: To assess long-term outcomes in patients aged 50-70 years undergoing MVR using contemporary mechanical and bioprosthetic valves. Methods: We performed a retrospective study using the TriNetX global database to identify patients aged 50 to 70 years who had primary isolated surgical MVR from 2014 to 2020. Patients who had concomitant or prior cardiac surgeries were excluded. Patients were stratified into 2 groups: mechanical and bioprosthetic, and a 1:1 propensity-score matching to control for baseline differences between the two groups was performed. The primary endpoint was all-cause mortality and secondary endpoints were stroke, major bleeding, and reoperation over a follow-up period of 8 years. Results: Propensity-score matching yielded 1,130 patients in each group. There were significantly higher rates of all-cause mortality, stroke, and major bleeding events in the mechanical group compared to the bioprosthetic valve. There was no significant difference between the two groups regarding reoperation (Table 1 and Figure 1). Conclusion: At an 8-year follow-up, the use of contemporary bioprosthetic valves for MVR in patients aged 50-70 years shows favorable all-cause mortality and lower rates of strokes and major bleeding with similar reoperation rates compared to mechanical valves.

Abstract 12670: Trends in Patients With COVID-19 and Device Related Infections: A National Inpatient Sample Trend From 2020

Background: Cardiac implantable electronic devices (CIED) are essential for managing arrhythmias, improving hemodynamics, and preventing sudden cardiac death. However, device-related infections (DRI) remain a significant complication of CIED and are associated with primary adverse outcomes. However, limited data exists on concomitant Covid-19 infection and its effects on outcomes of DRI. Methods: National Inpatient Sample 2020 was used to identify patients hospitalized for DRI based on ICD-10 codes. DRIs were further stratified into concomitant Covid-19 infected patients and non-Covid-19 infected groups. Logistic regression was used to compare in-hospital outcomes. Results: In 2020, there were 59,270 admissions for DRIs. 1,890 (3.2%) DRI cases were observed to have concomitant Covid-19 infection. Racial disparities observed included higher rates of DRI and concurrent Covid-19 infection in the African American (30.6% -vs- 20.2, p=0.002) and Hispanic (18.2% -vs- 9.4%, p=0.002) population. Lead extraction rates were lower in the Covid-19 infection with DRI group (5.33% -vs- 11.17%, p<0.001). Cases with DRI and concurrent Covid-19 infection also had a significantly longer length of stay (LOS, 21.6 -vs- 11.5 days, p<0.001), higher total hospital cost (305,644 -vs- 172,711, p<0.001), and higher mortality (23.1% -vs- 6.6%, p<0.001). This group was also observed to have increased needs for ICU level of care including higher proportion of ARDS, shock, mechanical ventilation and vasopressor use as listed in Table 1. Conclusion: DRIs with concurrent Covid-19 infection had higher all-cause mortality, complication rates, LOS and total hospital costs. Further research needs to be performed to delineate long-term outcomes in this patient population.

Abstract 14695: Artificial Intelligence Applied to the Electrocardiogram Predicts Outcomes in Patients With Severe Aortic Stenosis and Potential Cardiac Amyloidosis Undergoing Transcatheter Aortic Valve Replacement

Introduction: Cardiac amyloidosis (CA) has been suggested to be common (up to 16%) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). CA has poorer outcomes and its assessment in all TAVR patients may be costly and challenging. Hypothesis: CA may be screened for with an artificial intelligence (AI) clinical predictive model applied to pre-TAVR ECGs, and high probability (>50%) for CA may be associated with worse clinical outcomes. Methods: In this retrospective analysis of the Mayo institutional National Cardiovascular Disease Registry (NCDR)-TAVR, patients undergoing a TAVR between Jan-2012 and Dec-2017 were included. Pre-TAVR ECGs were analyzed by the AI predictive model for CA embedded in the EMR. EMRs were reviewed to assess for a clinical diagnosis of CA in those identified as high probability (>50%) by the AI tool. Clinical outcomes on 1 year follow-up were extracted from the NCDR-TAVR database and Kaplan-Meier curves were created to compare patients with high CA probability (≥50%) versus those with low probability (<50%). Results: Of 1070 patients who underwent TAVR (mean age 81.1± 8.5 years, 58.2% male), 263 (24.6%) had ≥50% probability for CA on pre-procedure ECG. Only 18 (1.7%) of these had clinical diagnosis of CA. In the survival analysis, high probability of CA by AI tool was associated with higher all-cause mortality (HR 1.60, 95%CI 1.09-2.34, p=0.01) and greater HF admissions (HR 1.59, 95%CI 1.08-2.35, p<0.01). Neither TIA/stroke nor myocardial infarction were statistically significant. MACE (TIA/stroke, myocardial infarction, heart failure admissions) was higher in the ≥50% CA probability group (HR 1.68, 95%CI 1.17-2.40, p<0.01), (Figure) . Conclusion: CA is clinically underdiagnosed in patients undergoing TAVR. AI applied to pre-TAVR ECGs suggesting higher probability for CA identifies a subgroup at higher risk of clinical events, who may benefit from further diagnostic evaluation for CA.

Abstract 14022: N-terminal Prohormone of B-type Natriuretic Peptide Levels Partly Mediate the Relationship of Advanced Hepatic Fibrosis With Mortality in Coronary Artery Disease

Background Advanced hepatic fibrosis (AHF) is associated with cardiac remodeling and adverse outcomes in patients with coronary artery disease (CAD). The mechanistic basis of this relationship and the contribution of the natriuretic peptide system is unclear. Hypothesis: The association of AHF with mortality in CAD is mediated by circulating N-terminal prohormone of B-type natriuretic peptide (NTproBNP) level. Methods: Patients undergoing cardiac catheterization for evaluation of CAD were enrolled in the Emory Cardiovascular Biobank and those with acute myocardial infarction, cirrhosis, and hepatocellular carcinoma were excluded. Plasma NTproBNP was measured, and Fibrosis-4 (FIB-4) index was calculated using age, alanine aminotransferase, aspartate aminotransferase, and platelet count. FIB-4 ≥2.67 was used to define AHF. Association of AHF and NTproBNP with all-cause mortality was studied using multivariable-adjusted Cox models and mediation analyses. Results: Study population included 3,432 patients with mean age 65 y and among them 32% were women, 24% were Black, and 15% had AHF. Median NTproBNP level was 2.5-fold higher among those with AHF (572, 95% CI 225-2203 pg/ml) compared with those without (223, 95% CI 93-689 pg/ml). AHF was independently associated with 49% higher all-cause mortality in multivariable-adjusted Cox models [HR(95% CI): 1.49 (1.26-1.77)]. NTproBNP stratified mortality risk associated with AHF ( Figure ). Patients with AHF and high NTproBNP (≥300 pg/ml) were at the highest risk, while risk in AHF and low NTproBNP (<300 pg/ml) group was similar to those without AHF and low NTproBNP. NTproBNP was independently associated with mortality risk and mediated 61% of the effect of AHF on mortality in causal mediation analysis. Conclusion: NTproBNP partly mediates the excess mortality associated with AHF in patients with CAD. Therapeutic strategies targeting the natriuretic peptide system may help improve outcomes in this high-risk group.

A Deep-Learning Algorithm-Enhanced Electrocardiogram Interpretation for Detecting Pulmonary Embolism.

The early diagnosis of pulmonary embolism (PE) remains a challenge. Electrocardiograms (ECGs) and D-dimer levels are used to screen potential cases. To develop a deep learning model (DLM) to detect PE using ECGs and investigate the clinical value of false detections in patients without PE. Among patients who visited the emergency department between 2011 and 2019, PE cases were identified through a review of medical records. Non-PE ECGs were collected from patients without a diagnostic code for PE. There were 113 PE and 51,456 non-PE ECGs in the training and validation sets for developing the DLM, respectively, and 27 PE and 13,105 non-PE cases in an independent testing set for performance validation. A human-machine competition was conducted from the testing set to compare the performance of the DLM with that of physicians. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were used to determine the diagnostic value. Survival analysis was used to assess the prognosis of the patients without PE, stratified by DLM prediction. The DLM was as effective as physicians in diagnosing PE, with 70.8% sensitivity and 69.7% specificity. The area under the ROC curve of DLM was 0.778 in the testing set and up to 0.9 with D-dimer and demographic data. The non-PE patients whose ECG was misclassified as PE by DLM had higher all-cause mortality [hazard ratio (HR) 2.13 (1.51-3.02)] and risk of non-cardiovascular hospitalization [HR 1.55 (1.42-1.68)] than those correctly classified. A DLM-enhanced ECG system may prompt PE recognition and provide prognostic outcomes in patients with false-positive predictions.

Evaluation of the contribution of county characteristics to the rural mortality disparity in cancer.

173 Background: Rural disparities in cancer outcomes have been widely evaluated, but limited evidence is available to characterize what characteristics of rural environments contribute to the increased risk of poor outcomes. Therefore, we propose to estimate the mediating effects of county characteristics on the relationship between urban/rural status and mortality among patients with cancer, identify county profiles, and determine problematic county profiles alongside rural settings. Methods: Patients with cancers (known to be associated with rural disparities) between 2000 and 2016 were assessed using Surveillance, Epidemiology and End Results data. We then linked these data to the 2010 County Health Rankings (CHR) which ranks US counties into quartiles within their state based on measures of health: morbidity, mortality, health behaviors, physical environment, socioeconomic status, clinical care environment. We dichotomized each domain as least healthy (quartiles 3 and 4) and most healthy (quartiles 1 and 2). Rurality was defined using the 2010 Rural-Urban Commuting Codes. Using mediation analyses, we estimated 1) the direct contribution of rurality to five-year all-cause and cancer-specific mortality and 2) the contribution of the rural effect indirectly through each CHR domain. We then used latent class analysis to identify county groupings based on rankings. Using flexible parametric survival models, we estimated the hazard of mortality associated with class membership, rurality and the interaction between rurality and class. Results: Among the 757,655 patients representing 596 counties, 51% were female, the most frequent diagnoses were breast and prostate (21%, respectively), 52% were diagnosed with localized disease, and 54% were diagnosed between 55y and 65y. When setting the mediator at least healthy (quartiles 3 and 4) premature death, clinical care, and physical environment, the rural patients had 17.9% to 20.2% less survival time compared to those in rural counties. Of this, 4.1% to 12.6% of the total excess risk was mediated by these characteristics. Three county classes were identified: Class 1 (28%) had consistently poor rankings, Class 2 (32%) had moderate rankings but poor clinical care, and Class 3 (41%) had consistently high rankings except for physical environment. Patients living in rural-high risk counties (class 1 and 2) saw higher all-cause mortality than those in urban-lower risk counties (reference class 3; HR, 1.04, 95%CI 1.01-1.08 and 1.07, 95%CI, 1.03-1.11). Conclusions: County characteristics mediated the relationship between rurality and mortality among patients with cancer. Counties with poor rankings had increased mortality risks regardless of rurality; however, the poor rankings elevated the mortality risk for those in rural counties. Access to care and physical environment may be actionable points of intervention in the pathway from rurality to mortality.

Incidence and outcomes of high bleeding risk patients with type 1 and type 2 myocardial infarction in a community-based cohort: Application of the Academic Research Consortium High Bleeding Risk Criteria

Background and aimsThe incidence and outcomes of high bleeding risk (HBR) patients in a community cohort according to the Academic Research Consortium (ARC) criteria is not known. We hypothesized that HBR is common and associated with worse outcomes for all-comers with myocardial infarction. MethodsWe prospectively collected all patients with cardiac troponin T > 99th percentile upper limit of normal (≥0.01 ng/mL) in Olmsted County between 2003 and 2012. Events were retrospectively classified as type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), or myocardial injury. Patients were further classified as HBR based on the “ARC-HBR definition.” Outcomes included all-cause mortality, cardiovascular mortality, recurrent MI, stroke, and major bleeding. Results2419 patients were included in the final study; 1365 were classified as T1MI and 1054 as T2MI. Patients were followed for a median of 5.5 years. ARC-HBR was more common in T2MI than T1MI (73% vs 46%, p < 0.001). Among patients with T1MI, HBR was associated with higher all-cause mortality (HR 3.7, 95% CI 3.2–4.5, p < 0.001), cardiovascular mortality (4.7, 3.6–6.3, p < 0.001), recurrent MI (2.1, 1.6–2.7, p < 0.001), stroke (4.9, 2.9–8.4, p < 0.001), and major bleeding (6.5, 3.7–11.4, p < 0.001). For T2MI, HBR was similarly associated with higher all-cause mortality (HR 2.1, 95% CI 1.8–2.5, p < 0.001), cardiovascular mortality (2.7, 1.8–4.0, p < 0.001), recurrent MI (1.7, 1.1–2.6, p = 0.02) and major bleeding (HR 15.6, 3.8–63.8, p < 0.001). ConclusionHBR is common among unselected patients with T1MI and T2MI and is associated with increased overall and cardiovascular mortality, recurrent cardiovascular events, and major bleeding on long-term follow up.

Association between the first 24 hours PaCO2 and all-cause mortality of patients suffering from sepsis-associated encephalopathy after ICU admission: A retrospective study.

The relationship between the levels of the first 24-h PaCO2 and the prognosis of sepsis-associated encephalopathy (SAE) remains unclear, and the first 24-h optimal target for PaCO2 is currently inconclusive. This study was performed to investigate the correlation between PaCO2 and all-cause mortality for SAE patients, establish a reference range of the initial 24-hour PaCO2 for clinicians in critical care, and explain the possible pathophysiological mechanisms of abnormal PaCO2 levels as a higher mortality risk factor for SAE. The baseline information and clinical data of patients were extracted from the fourth edition Medical Information Mart for Intensive Care database (MIMIC-IV 2.0). Multivariate logistic regressions were performed to assess the relationship between PaCO2 and all-cause mortality of SAE. Additionally, restricted cubic splines, Kaplan-Meier Survival analyses, propensity score matching (PSM) analyses, and subgroup analyses were conducted. A total of 5471 patients were included in our cohort. In the original and matched cohort, multivariate logistic regression analysis showed that normocapnia and mild hypercapnia may be associated with a more favorable prognosis of SAE patients, and survival analysis supported the findings. In addition, a U-shaped association emerged when examining the initial 24-hour PaCO2 levels in relation to 30-day, 60-day, and 90-day mortality using restricted cubic splines, with an average cut-off value of 36.3mmHg (P for nonlinearity<0.05). Below the cut-off value, higher PaCO2 was associated with lower all-cause mortality, while above the cut-off value, higher PaCO2 was associated with higher all-cause mortality. Subsequent subgroup analyses revealed similar results for the subcohort of GCS≤8 compared to the original cohort. Additionally, when examining the subcohort of GCS>8, a L-shaped relationship between PaCO2 and the three clinical endpoints emerged, in contrast to the previously observed U-shaped pattern. The findings from the subcohort of GCS>8 suggested that patients experiencing hypocapnia had a more unfavorable prognosis, which aligns with the results obtained from corresponding multivariate logistic regression analyses. The retrospective study revealed the association between the first 24-h PaCO2 and all-cause mortality risk (30-day, 60-day, and 90-day) for patients with SAE in ICU. The range (35mmHg-50mmHg) of PaCO2 may be the optimal target for patients with SAE in clinical practice.

Reduced-Dose Rivaroxaban Is Associated with Lower All-Cause Mortality in Older Patients with Nonvalvular Atrial Fibrillation.

Reduced-dose rivaroxaban (10 mg) was used in the J-ROCKET AF trial, demonstrating safety in the Asian population. It remains unclear whether treatment with reduced-dose versus full-dose rivaroxaban (20 mg/15 mg) is associated with all-cause mortality in older patients with nonvalvular atrial fibrillation. Proposed: To evaluate the effects of reduced-dose rivaroxaban on all-cause mortality in patients over 85. We retrospectively enrolled medical records representing the period from October 2012 to November 2016. The 2 × 2 factorial design incorporated age (≥85 vs. <85) and rivaroxaban use (reduced vs. full dose). The primary study outcomes were all-cause and cardiac-related mortality. The study enrolled 2386 patients with a mean age of 76.6 ± 10.4 years; 51.8% were male. In the ≥85 group (n = 593), the reduced-dose subgroup had lower all-cause (5.3% vs. 10.6%, p = 0.02) and cardiac-related mortality (1.9% vs. 5.1%, p = 0.04), whereas the younger patients receiving reduced-dose rivaroxaban had higher all-cause mortality (3.7% vs. 1.8%, p = 0.01) but no difference in cardiac-related mortality (1.2% vs. 0.7%, p = 0.33). The rate of hospitalization for heart failure was significantly lower in the elderly group with reduced-dose rivaroxaban (7.2% vs. 15.7%, p < 0.01) but not in the younger group. After adjusting for confounders in the older group, treatment with reduced-dose rivaroxaban was associated with lower risk of all-cause mortality (adjusted HR (aHR): 0.40, 95% CI: 0.21-0.74, p < 0.01) and hospitalization for heart failure (aHR: 0.54, 95% CI: 0.29-0.99, p = 0.05). No associations were found between rivaroxaban dose and cardiac-related mortality in either group, nor between younger age and any outcome. Reduced-dose rivaroxaban was associated with lower risks of all-cause mortality and hospitalization for heart failure in older patients with nonvalvular atrial fibrillation. Future studies can investigate the effect of reduced-dose rivaroxaban on prognoses in elderly individuals ≥85 years in the west.

Pericardiocentesis Outcomes in Patients With Pulmonary Hypertension: A Nationwide Analysis from the United States

Pericardiocentesis (PC) in patients with pulmonary hypertension (PH) and pericardial effusions has unclear benefits because it has been associated with acute hemodynamic collapse and increased mortality. Data on in-hospital outcomes in this population are limited. The National Inpatient Sample database was used to identify adult patients who underwent PC during hospitalizations between 2016 and 2020. Data were stratified by the presence or absence of PH. A multivariate regression model and case-control matching was used to estimate the association of PH with PC in-hospital outcomes. A total of 95,665 adults with a procedure diagnosis of PC were included, of whom 7,770 had PH. Patients with PH tended to be older (aged 67 ± 15.7 years) and female (56%) and less frequently presented with tamponade (44.9% vs 52.4%). Patients with PH had significantly higher rates of chronic kidney disease, coronary artery disease, heart failure, and chronic lung disease, among other co-morbidities. In the multivariate analysis, PC in PH was associated with higher all-cause mortality (adjusted odds ratio [aOR] 1.40, confidence interval [CI] 1.30 to 1.51) and higher rates of postprocedure shock (aOR 1.53, CI 1.30 to 1.81) than patients without PH. Mortality was higher in those with pulmonary arterial hypertension than other nonpulmonary arterial hypertension PH groups (aOR 2.35, 95% CI 1.46 to 3.80, p <0.001). The rates of cardiogenic shock (aOR 1.49, 95% CI 1.38 to 1.61), acute respiratory failure (aOR 1.56, 95% CI 1.48 to 1.64), and mechanical circulatory support use (aOR 1.86, 95% CI 1.63 to 2.12) were also higher in patients with PH. There was no significant volume-outcome relation between hospitals with a high per-annum pericardiocentesis volume compared with low-volume hospitals in these patients. In conclusion, PC is associated with increased in-hospital mortality and higher rates of cardiovascular complications in patients with PH, regardless of the World Health Organization PH group.

The impact of sex differences on 3-year outcomes of patients with non-ST-segment elevation myocardial infarction after successful stent implantation according to symptom-to-balloon time

BackgroundBecause no data are available, we compared the 3-year outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) based on sex and symptom-to-balloon time (SBT). MethodsThis study included 4910 patients who were divided into two groups based on SBT: SBT <48 h (n = 3,293, 67.1%) and SBT ≥48 h (n = 1,617, 32.9%). The primary outcome was all-cause death during the 3-year follow-up period. The secondary outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction, or repeat coronary revascularization. ResultsAfter adjustment, the in-hospital mortality rates for males and females in the SBT <48 h and SBT ≥48 h groups were similar. During a 3-year follow-up period, females in the SBT <48 h group had significantly higher rates of all-cause death (adjusted hazard ratio [aHR], 1.482; P = 0.006), cardiac death (CD, aHR, 1.617; P = 0.009), and MACE (aHR, 1.268; P = 0.024) than those males in the same groups. Females and males in the SBT ≥48 h group did not differ significantly in the primary and secondary outcomes. In males, the rates of all-cause death (P = 0.008) and CD (P = 0.024) were significantly higher in the SBT ≥48 h group than in the SBT <48 h group. ConclusionsThis study has identified a higher 3-year mortality rate in female patients with NSTEMI and SBT <48 h compared to their male counterparts. As such, a more preventive approach may be required to reduce mortality in these female patients.